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  • Molecular Sequence Data  (3,676)
  • Cell Line  (2,037)
  • Chemical Engineering
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  • American Association for the Advancement of Science (AAAS)  (5,527)
  • 1
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-07-08
    Description: Separation and purification are critical industrial processes for separating components of chemical mixtures, and these processes account for about half of industrial energy usage (1). Gas mixtures of compounds with very similar physical properties are particularly difficult to separate. On pages 137 and 141 of this issue, Cadiau et al. (2) and Cui et al. (3), respectively, show that microporous materials can be designed to have high adsorption capacity and selectivity for particular hydrocarbons, enabling energy-efficient separation. Author: Jerry Y. S. Lin
    Keywords: Chemistry
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  • 2
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-05-27
    Description: Biomass-degrading microorganisms use lytic polysaccharide monooxygenase (LPMO) enzymes to help digest cellulose, chitin, and starch. By cleaving otherwise inaccessible crystalline cellulose chains, these enzymes provide access to hydrolytic enzymes. LPMOs are of interest to biotechnology because efficient depolymerization of cellulose is a major bottleneck for the production of biologically based chemicals and fuels. On page 1098 of this issue, Kracher et al. (1) compare LPMO-reducing substrates in fungi from different taxonomic groups and lifestyles, based on both biochemical and genomic evidence. The results provide insights into reductive activation of LPMO that are important for developing more efficient industrial enzymes for lignocellulose biorefineries. Author: Angel T. Martínez
    Keywords: Chemistry
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  • 3
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-03-25
    Description: Author: Marc S. Lavine
    Keywords: Chemistry
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  • 4
    Publication Date: 2002-04-16
    Description: Natural killer (NK) cells express inhibitory receptors for major histocompatibility complex (MHC) class I antigens, preventing attack against healthy cells. Mouse cytomegalovirus (MCMV) encodes an MHC-like protein (m157) that binds to an inhibitory NK cell receptor in certain MCMV-susceptible mice. In MCMV-resistant mice, this viral protein engages a related activating receptor (Ly49H) and confers host protection. These activating and inhibitory receptors are highly homologous, suggesting the possibility that one evolved from the other in response to selective pressure imposed by the pathogen.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Arase, Hisashi -- Mocarski, Edward S -- Campbell, Ann E -- Hill, Ann B -- Lanier, Lewis L -- AI30363/AI/NIAID NIH HHS/ -- CA89294/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2002 May 17;296(5571):1323-6. Epub 2002 Apr 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology and the Cancer Research Institute, University of California San Francisco, San Francisco, CA 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11950999" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Animals ; Antigens, Ly/chemistry/genetics/*immunology/metabolism ; Cell Line ; Coculture Techniques ; Disease Susceptibility ; Evolution, Molecular ; Herpesviridae Infections/*immunology ; Histocompatibility Antigens Class I/immunology ; Hybridomas ; Immunity, Innate ; Interferon-gamma/biosynthesis ; Killer Cells, Natural/*immunology ; Lectins, C-Type ; Ligands ; Lymphocyte Activation ; Membrane Glycoproteins/chemistry/genetics/*immunology/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Muromegalovirus/genetics/*immunology/metabolism ; NK Cell Lectin-Like Receptor Subfamily A ; Protein Binding ; Receptors, Immunologic/chemistry/genetics/*immunology/metabolism ; Receptors, NK Cell Lectin-Like ; Recombinant Fusion Proteins/metabolism ; Transfection ; Viral Proteins/chemistry/genetics/*immunology/metabolism
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  • 5
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-02-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vogelstein, Bert -- Alberts, Bruce -- Shine, Kenneth -- New York, N.Y. -- Science. 2002 Feb 15;295(5558):1237.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Kimmel Cancer Center at Johns Hopkins University, Baltimore, MD 21231, USA. vogelbe@welch.jhu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11847324" target="_blank"〉PubMed〈/a〉
    Keywords: Bioethical Issues ; Cell Line ; *Cloning, Organism/legislation & jurisprudence ; Embryo Research ; Embryo, Mammalian/*cytology ; Humans ; *Nuclear Transfer Techniques ; *Stem Cells ; *Terminology as Topic ; United States
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  • 6
    Publication Date: 2002-10-05
    Description: The detection of single-nucleotide polymorphisms in pathogenic microorganisms has normally been carried out by trial and error. Here we show that DNA hybridization with high-density oligonucleotide arrays provides rapid and convenient detection of single-nucleotide polymorphisms in Plasmodium falciparum, despite its exceptionally high adenine-thymine (AT) content (82%). A disproportionate number of polymorphisms are found in genes encoding proteins associated with the cell membrane. These genes are targets for only 22% of the oligonucleotide probes but account for 69% of the polymorphisms. Genetic variation is also enriched in subtelomeric regions, which account for 22% of the chromosome but 76% of the polymorphisms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Volkman, Sarah K -- Hartl, Daniel L -- Wirth, Dyann F -- Nielsen, Kaare M -- Choi, Mehee -- Batalov, Serge -- Zhou, Yingyao -- Plouffe, David -- Le Roch, Karine G -- Abagyan, Ruben -- Winzeler, Elizabeth A -- GM61351/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2002 Oct 4;298(5591):216-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12364807" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Chromosomes/genetics ; DNA, Protozoan/genetics ; *Genes, Protozoan ; Genetic Variation ; Genome, Protozoan ; Membrane Proteins/*genetics ; Molecular Sequence Data ; Nucleic Acid Hybridization ; Oligonucleotide Probes ; Plasmodium falciparum/*genetics ; *Polymorphism, Single Nucleotide ; Protozoan Proteins/*genetics ; Sequence Analysis, DNA
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  • 7
    Publication Date: 2002-04-06
    Description: Higher order chromatin structure presents a barrier to the recognition and repair of DNA damage. Double-strand breaks (DSBs) induce histone H2AX phosphorylation, which is associated with the recruitment of repair factors to damaged DNA. To help clarify the physiological role of H2AX, we targeted H2AX in mice. Although H2AX is not essential for irradiation-induced cell-cycle checkpoints, H2AX-/- mice were radiation sensitive, growth retarded, and immune deficient, and mutant males were infertile. These pleiotropic phenotypes were associated with chromosomal instability, repair defects, and impaired recruitment of Nbs1, 53bp1, and Brca1, but not Rad51, to irradiation-induced foci. Thus, H2AX is critical for facilitating the assembly of specific DNA-repair complexes on damaged DNA.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721576/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721576/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Celeste, Arkady -- Petersen, Simone -- Romanienko, Peter J -- Fernandez-Capetillo, Oscar -- Chen, Hua Tang -- Sedelnikova, Olga A -- Reina-San-Martin, Bernardo -- Coppola, Vincenzo -- Meffre, Eric -- Difilippantonio, Michael J -- Redon, Christophe -- Pilch, Duane R -- Olaru, Alexandru -- Eckhaus, Michael -- Camerini-Otero, R Daniel -- Tessarollo, Lino -- Livak, Ferenc -- Manova, Katia -- Bonner, William M -- Nussenzweig, Michel C -- Nussenzweig, Andre -- Z99 CA999999/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2002 May 3;296(5569):922-7. Epub 2002 Apr 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11934988" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; B-Lymphocytes/immunology/physiology ; Base Sequence ; Cell Aging ; Cell Cycle ; Cells, Cultured ; *Chromosome Aberrations ; DNA Damage ; *DNA Repair ; Female ; Gene Targeting ; Histones/chemistry/*genetics/*physiology ; Immunoglobulin Class Switching ; Infertility, Male/genetics/physiopathology ; Lymphocyte Count ; Male ; Meiosis ; Mice ; Mice, Knockout ; Molecular Sequence Data ; Mutation ; Phosphorylation ; *Recombination, Genetic ; Spermatocytes/physiology ; T-Lymphocytes/immunology/physiology
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  • 8
    Publication Date: 2002-06-22
    Description: Positive-strand RNA viruses such as poliovirus replicate their genomes on intracellular membranes of their eukaryotic hosts. Electron microscopy has revealed that purified poliovirus RNA-dependent RNA polymerase forms planar and tubular oligomeric arrays. The structural integrity of these arrays correlates with cooperative RNA binding and RNA elongation and is sensitive to mutations that disrupt intermolecular contacts predicted by the polymerase structure. Membranous vesicles isolated from poliovirus-infected cells contain structures consistent with the presence of two-dimensional polymerase arrays on their surfaces during infection. Therefore, host cytoplasmic membranes may function as physical foundations for two-dimensional polymerase arrays, conferring the advantages of surface catalysis to viral RNA replication.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lyle, John M -- Bullitt, Esther -- Bienz, Kurt -- Kirkegaard, Karla -- AI-42119/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2002 Jun 21;296(5576):2218-22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12077417" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Binding Sites ; Catalysis ; Crystallography, X-Ray ; HeLa Cells ; Humans ; Hydrogen-Ion Concentration ; Inclusion Bodies, Viral/metabolism/ultrastructure ; Microscopy, Electron ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Nucleic Acid Conformation ; Poliovirus/*enzymology/physiology ; Protein Conformation ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; RNA Replicase/*chemistry/isolation & purification/*metabolism/ultrastructure ; RNA, Viral/biosynthesis/*metabolism ; Viral Core Proteins/metabolism ; Virus Replication
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  • 9
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-05-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Demaine, Linda J -- Fellmeth, Aaron X -- New York, N.Y. -- Science. 2003 May 30;300(5624):1375-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉RAND, Santa Monica, CA 90401, USA. demaine@rand.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12775825" target="_blank"〉PubMed〈/a〉
    Keywords: Aluminum Oxide ; Chemical Phenomena ; Chemistry ; Natural Science Disciplines ; Patents as Topic/*legislation & jurisprudence ; Plant Extracts ; Plant Roots ; Titanium ; United States
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  • 10
    Publication Date: 2002-12-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Funes, Soledad -- Davidson, Edgar -- Reyes-Prieto, Adrian -- Magallon, Susana -- Herion, Pascal -- King, Michael P -- Gonzalez-Halphen, Diego -- HL59646/HL/NHLBI NIH HHS/ -- TW01176/TW/FIC NIH HHS/ -- New York, N.Y. -- Science. 2002 Dec 13;298(5601):2155.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Instituto de Fisiologia Celular, Universidad Nacional Autonoma de Mexico (UNAM), 04510 D.F., Mexico.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12481129" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Apicomplexa/enzymology/*genetics/ultrastructure ; *Biological Evolution ; Cell Nucleus/genetics ; Chlamydomonas reinhardtii/enzymology/genetics ; Chlorophyta/enzymology/*genetics ; Cloning, Molecular ; DNA, Mitochondrial/genetics ; Electron Transport Complex IV/chemistry/*genetics ; *Gene Transfer, Horizontal ; Genes ; Genes, Protozoan ; Molecular Sequence Data ; Phylogeny ; Plastids/*genetics ; Symbiosis ; Toxoplasma/enzymology/genetics
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  • 11
    Publication Date: 2002-02-09
    Description: Double-stranded RNA-mediated gene interference (RNAi) in Caenorhabditis elegans systemically inhibits gene expression throughout the organism. To investigate how gene-specific silencing information is transmitted between cells, we constructed a strain that permits visualization of systemic RNAi. We used this strain to identify systemic RNA interference-deficient (sid) loci required to spread gene-silencing information between tissues but not to initiate or maintain an RNAi response. One of these loci, sid-1, encodes a conserved protein with predicted transmembrane domains. SID-1 is expressed in cells sensitive to RNAi, is localized to the cell periphery, and is required cell-autonomously for systemic RNAi.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Winston, William M -- Molodowitch, Christina -- Hunter, Craig P -- New York, N.Y. -- Science. 2002 Mar 29;295(5564):2456-9. Epub 2002 Feb 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11834782" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Animals, Genetically Modified ; Caenorhabditis elegans/embryology/*genetics/metabolism ; Caenorhabditis elegans Proteins/chemistry/*genetics/*physiology ; Calmodulin-Binding Proteins/genetics ; Cytoplasm/metabolism ; Embryo, Nonmammalian/physiology ; *Gene Silencing ; Genes, Helminth ; Germ Cells/metabolism ; Green Fluorescent Proteins ; Intestines/metabolism ; Luminescent Proteins/genetics ; Membrane Proteins/chemistry/*genetics/*physiology ; Molecular Sequence Data ; Mosaicism ; Muscle Proteins/genetics ; Muscles/metabolism ; Mutation ; Protein Structure, Tertiary ; RNA, Double-Stranded/*genetics/metabolism ; RNA, Helminth/*genetics/metabolism ; Recombinant Fusion Proteins/metabolism ; Transgenes
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  • 12
    Publication Date: 2003-04-26
    Description: Tubular nanostructures are suggested to have a wide range of applications in nanotechnology. We report our observation of the self-assembly of a very short peptide, the Alzheimer's beta-amyloid diphenylalanine structural motif, into discrete and stiff nanotubes. Reduction of ionic silver within the nanotubes, followed by enzymatic degradation of the peptide backbone, resulted in the production of discrete nanowires with a long persistence length. The same dipeptide building block, made of D-phenylalanine, resulted in the production of enzymatically stable nanotubes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reches, Meital -- Gazit, Ehud -- New York, N.Y. -- Science. 2003 Apr 25;300(5619):625-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12714741" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Amyloid beta-Peptides/chemistry ; Biosensing Techniques ; Birefringence ; Dipeptides/*chemistry ; Microscopy, Electron ; Microscopy, Electron, Scanning ; Molecular Sequence Data ; *Nanotechnology ; Oxidation-Reduction ; Protein Conformation ; Silver ; Solubility ; Spectroscopy, Fourier Transform Infrared
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  • 13
    Publication Date: 2003-08-09
    Description: Amyotrophic lateral sclerosis (ALS) is a progressive, lethal neuromuscular disease that is associated with the degeneration of spinal and brainstem motor neurons, leading to atrophy of limb, axial, and respiratory muscles. The cause of ALS is unknown, and there is no effective therapy. Neurotrophic factors are candidates for therapeutic evaluation in ALS. Although chronic delivery of molecules to the central nervous system has proven difficult, we recently discovered that adeno-associated virus can be retrogradely transported efficiently from muscle to motor neurons of the spinal cord. We report that insulin-like growth factor 1 prolongs life and delays disease progression, even when delivered at the time of overt disease symptoms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaspar, Brian K -- Llado, Jeronia -- Sherkat, Nushin -- Rothstein, Jeffrey D -- Gage, Fred H -- AG12992/AG/NIA NIH HHS/ -- AG21876/AG/NIA NIH HHS/ -- NS33958/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2003 Aug 8;301(5634):839-42.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12907804" target="_blank"〉PubMed〈/a〉
    Keywords: Amyotrophic Lateral Sclerosis/pathology/physiopathology/*therapy ; Animals ; Apoptosis ; Base Sequence ; Caspase 9 ; Caspases/metabolism ; Cell Count ; Dependovirus/*genetics ; Disease Models, Animal ; Disease Progression ; Gene Transfer Techniques ; *Genetic Therapy ; *Genetic Vectors/administration & dosage ; Glial Cell Line-Derived Neurotrophic Factor ; Green Fluorescent Proteins ; Insulin-Like Growth Factor I/*genetics ; Luminescent Proteins/genetics ; Male ; Mice ; Mice, Transgenic ; Molecular Sequence Data ; Motor Neurons/pathology/virology ; Muscle, Skeletal/virology ; Nerve Growth Factors/genetics ; *Protein-Serine-Threonine Kinases ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins c-akt ; Random Allocation ; Spinal Cord/chemistry/pathology/virology ; Superoxide Dismutase/genetics/metabolism ; Ubiquitin/analysis
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  • 14
    Publication Date: 2003-10-04
    Description: Analysis of the human and mouse genomes identified an abundance of conserved non-genic sequences (CNGs). The significance and evolutionary depth of their conservation remain unanswered. We have quantified levels and patterns of conservation of 191 CNGs of human chromosome 21 in 14 mammalian species. We found that CNGs are significantly more conserved than protein-coding genes and noncoding RNAS (ncRNAs) within the mammalian class from primates to monotremes to marsupials. The pattern of substitutions in CNGs differed from that seen in protein-coding and ncRNA genes and resembled that of protein-binding regions. About 0.3% to 1% of the human genome corresponds to a previously unknown class of extremely constrained CNGs shared among mammals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dermitzakis, Emmanouil T -- Reymond, Alexandre -- Scamuffa, Nathalie -- Ucla, Catherine -- Kirkness, Ewen -- Rossier, Colette -- Antonarakis, Stylianos E -- New York, N.Y. -- Science. 2003 Nov 7;302(5647):1033-5. Epub 2003 Oct 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Medical Genetics and National Center of Competence in Research (NCCR) Frontiers in Genetics, University of Geneva Medical School and University Hospitals, 1211 Geneva, Switzerland. Emmanouil.Dermitzakis@medecine.unige.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14526086" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Chromosomes, Human, Pair 21/*genetics ; Chromosomes, Mammalian/*genetics ; *Conserved Sequence ; DNA, Intergenic/*genetics ; Discriminant Analysis ; *Evolution, Molecular ; Female ; Genetic Code ; Genome ; Humans ; Male ; Mammals/*genetics ; Molecular Sequence Data ; Polymerase Chain Reaction ; Proteins/genetics ; RNA, Untranslated/genetics ; Selection, Genetic ; Sequence Alignment ; Species Specificity ; Time ; Transcription, Genetic
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  • 15
    Publication Date: 2003-12-20
    Description: Approximately 80% of the maize genome comprises highly repetitive sequences interspersed with single-copy, gene-rich sequences, and standard genome sequencing strategies are not readily adaptable to this type of genome. Methodologies that enrich for genic sequences might more rapidly generate useful results from complex genomes. Equivalent numbers of clones from maize selected by techniques called methylation filtering and High C0t selection were sequenced to generate approximately 200,000 reads (approximately 132 megabases), which were assembled into contigs. Combination of the two techniques resulted in a sixfold reduction in the effective genome size and a fourfold increase in the gene identification rate in comparison to a nonenriched library.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Whitelaw, C A -- Barbazuk, W B -- Pertea, G -- Chan, A P -- Cheung, F -- Lee, Y -- Zheng, L -- van Heeringen, S -- Karamycheva, S -- Bennetzen, J L -- SanMiguel, P -- Lakey, N -- Bedell, J -- Yuan, Y -- Budiman, M A -- Resnick, A -- Van Aken, S -- Utterback, T -- Riedmuller, S -- Williams, M -- Feldblyum, T -- Schubert, K -- Beachy, R -- Fraser, C M -- Quackenbush, J -- New York, N.Y. -- Science. 2003 Dec 19;302(5653):2118-20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Institute for Genomic Research (TIGR), 9712 Medical Center Drive, Rockville, MD 20850, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14684821" target="_blank"〉PubMed〈/a〉
    Keywords: Chromosomes, Plant/genetics ; Cloning, Molecular ; Computational Biology ; Contig Mapping ; DNA Methylation ; DNA, Plant/genetics ; Databases, Nucleic Acid ; Expressed Sequence Tags ; Gene Dosage ; Gene Library ; *Genes, Plant ; *Genome, Plant ; Molecular Sequence Data ; Repetitive Sequences, Nucleic Acid ; Retroelements ; Sequence Alignment ; Sequence Analysis, DNA/*methods ; Transcription, Genetic ; Zea mays/*genetics
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  • 16
    Publication Date: 2002-12-10
    Description: The formation and patterning of mesoderm during mammalian gastrulation require the activity of Nodal, a secreted mesoderm-inducing factor of the transforming growth factor-beta (TGF-beta) family. Here we show that the transcriptional corepressor DRAP1 has a very specific role in regulation of Nodal activity during mouse embryogenesis. We find that loss of Drap1 leads to severe gastrulation defects that are consistent with increased expression of Nodal and can be partially suppressed by Nodal heterozygosity. Biochemical studies indicate that DRAP1 interacts with and inhibits DNA binding by the winged-helix transcription factor FoxH1 (FAST), a critical component of a positive feedback loop for Nodal activity. We propose that DRAP1 limits the spread of a morphogenetic signal by down-modulating the response to the Nodal autoregulatory loop.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Iratni, Rabah -- Yan, Yu-Ting -- Chen, Canhe -- Ding, Jixiang -- Zhang, Yi -- Price, Sandy M -- Reinberg, Danny -- Shen, Michael M -- New York, N.Y. -- Science. 2002 Dec 6;298(5600):1996-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Biochemistry, Division of Nucleic Acids Enzymology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12471260" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Cell Line ; Crosses, Genetic ; DNA/metabolism ; DNA-Binding Proteins/metabolism ; *Embryonic and Fetal Development ; Female ; Forkhead Transcription Factors ; Gastrula/*physiology ; Gene Expression Regulation, Developmental ; Gene Targeting ; Heterozygote ; In Situ Hybridization ; Left-Right Determination Factors ; Male ; Mesoderm/cytology/physiology ; Mice ; Morphogenesis ; Mutation ; Nodal Protein ; Phenotype ; Protein Binding ; RNA Interference ; Recombinant Fusion Proteins/metabolism ; Repressor Proteins/genetics/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; *Signal Transduction ; Transcription Factors/metabolism ; Transforming Growth Factor beta/genetics/*metabolism
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  • 17
    Publication Date: 2002-04-27
    Description: Little is known of how plant disease resistance (R) proteins recognize pathogens and activate plant defenses. Rcr3 is specifically required for the function of Cf-2, a Lycopersicon pimpinellifolium gene bred into cultivated tomato (Lycopersicon esculentum) for resistance to Cladosporium fulvum. Rcr3 encodes a secreted papain-like cysteine endoprotease. Genetic analysis shows Rcr3 is allelic to the L. pimpinellifolium Ne gene, which suppresses the Cf-2-dependent autonecrosis conditioned by its L. esculentum allele, ne (necrosis). Rcr3 alleles from these two species encode proteins that differ by only seven amino acids. Possible roles of Rcr3 in Cf-2-dependent defense and autonecrosis are discussed.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kruger, Julia -- Thomas, Colwyn M -- Golstein, Catherine -- Dixon, Mark S -- Smoker, Matthew -- Tang, Saijun -- Mulder, Lonneke -- Jones, Jonathan D G -- New York, N.Y. -- Science. 2002 Apr 26;296(5568):744-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Sainsbury Laboratory, John Innes Centre, Norwich NR4 7UH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11976458" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Sequence ; Base Sequence ; Cladosporium/*physiology ; Cloning, Molecular ; Cysteine Endopeptidases/chemistry/*genetics/*metabolism ; Cysteine Proteinase Inhibitors/pharmacology ; Gene Expression Regulation, Plant ; *Genes, Plant ; Immunity, Innate ; Leucine/analogs & derivatives/pharmacology ; Lycopersicon esculentum/*enzymology/genetics/*microbiology/physiology ; Molecular Sequence Data ; Mutation ; Phenotype ; *Plant Diseases ; Plant Leaves/enzymology ; Plant Proteins/*metabolism ; Plants, Genetically Modified ; Promoter Regions, Genetic ; Recombinant Fusion Proteins/chemistry/metabolism ; Tobacco/genetics ; Transgenes
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  • 18
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-12-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gallo, Robert C -- New York, N.Y. -- Science. 2002 Nov 29;298(5599):1728-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Human Virology and Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12459576" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Serodiagnosis/history ; Acquired Immunodeficiency Syndrome/diagnosis/*history/immunology/virology ; CD4-Positive T-Lymphocytes/virology ; Cell Line ; Cells, Cultured ; France ; *HIV/classification/isolation & purification/physiology ; History, 20th Century ; Human T-lymphotropic virus 1/isolation & purification/physiology ; Human T-lymphotropic virus 2/isolation & purification/physiology ; Humans ; Interleukin-2/history/isolation & purification/physiology ; Patents as Topic/history ; RNA-Directed DNA Polymerase/history/isolation & purification/metabolism ; United States ; Virus Cultivation
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  • 19
    Publication Date: 2002-04-06
    Description: The conserved Sir2 family of proteins has protein deacetylase activity that is dependent on NAD (the oxidized form of nicotinamide adenine dinucleotide). Although histones are one likely target for the enzymatic activity of eukaryotic Sir2 proteins, little is known about the substrates and roles of prokaryotic Sir2 homologs. We reveal that an archaeal Sir2 homolog interacts specifically with the major archaeal chromatin protein, Alba, and that Alba exists in acetylated and nonacetylated forms. Furthermore, we show that Sir2 can deacetylate Alba and mediate transcriptional repression in a reconstituted in vitro transcription system. These data provide a paradigm for how Sir2 family proteins influence transcription and suggest that modulation of chromatin structure by acetylation arose before the divergence of the archaeal and eukaryotic lineages.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bell, Stephen D -- Botting, Catherine H -- Wardleworth, Benjamin N -- Jackson, Stephen P -- White, Malcolm F -- New York, N.Y. -- Science. 2002 Apr 5;296(5565):148-51.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council (MRC) Cancer Cell Unit, The Hutchison/MRC Research Centre, Hills Road, Cambridge, CB2 2QH, UK. sdb@mole.bio.cam.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11935028" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Amino Acid Sequence ; Archaeal Proteins/*chemistry/*metabolism ; Chromatin/*metabolism ; DNA/metabolism ; Gene Expression Regulation, Archaeal ; Histone Deacetylases/chemistry/*metabolism ; Molecular Sequence Data ; Molecular Weight ; Protein Binding ; Recombinant Fusion Proteins/chemistry/metabolism ; *Silent Information Regulator Proteins, Saccharomyces cerevisiae ; Sirtuin 2 ; Sirtuins ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Sulfolobus/*chemistry/genetics/metabolism ; Templates, Genetic ; Trans-Activators/chemistry/*metabolism ; Transcription, Genetic
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  • 20
    Publication Date: 2003-04-26
    Description: The active-site cysteine of peroxiredoxins is selectively oxidized to cysteine sulfinic acid during catalysis, which leads to inactivation of peroxidase activity. This oxidation was thought to be irreversible. However, by metabolic labeling of mammalian cells with 35S, we show that the sulfinic form of peroxiredoxin I, produced during the exposure of cells to H2O2, is rapidly reduced to the catalytically active thiol form. The mammalian cells' ability to reduce protein sulfinic acid might serve as a mechanism to repair oxidatively damaged proteins or represent a new type of cyclic modification by which the function of various proteins is regulated.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Woo, Hyun Ae -- Chae, Ho Zoon -- Hwang, Sung Chul -- Yang, Kap-Seok -- Kang, Sang Won -- Kim, Kanghwa -- Rhee, Sue Goo -- New York, N.Y. -- Science. 2003 Apr 25;300(5619):653-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Cell Signaling Research and Division of Molecular Life Sciences, Ewha Womans University, Seoul 120-750, Korea.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12714748" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Catalysis ; Cell Line ; Cycloheximide/pharmacology ; Cysteine/*analogs & derivatives/*metabolism ; Dimerization ; HeLa Cells ; Humans ; Hydrogen Peroxide/*metabolism ; Methionine/metabolism ; Mice ; Neurotransmitter Agents ; Oxidation-Reduction ; Peroxidases/chemistry/*metabolism ; Peroxiredoxins ; Protein Synthesis Inhibitors/pharmacology ; Spectrometry, Mass, Electrospray Ionization ; Sulfhydryl Compounds/metabolism ; Sulfinic Acids/metabolism ; Tumor Cells, Cultured
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 21
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-07-26
    Description: It is well known that hunting dramatically reduced all baleen whale populations, yet reliable estimates of former whale abundances are elusive. Based on coalescent models for mitochondrial DNA sequence variation, the genetic diversity of North Atlantic whales suggests population sizes of approximately 240,000 humpback, 360,000 fin, and 265,000 minke whales. Estimates for fin and humpback whales are far greater than those previously calculated for prewhaling populations and 6 to 20 times higher than present-day population estimates. Such discrepancies suggest the need for a quantitative reevaluation of historical whale populations and a fundamental revision in our conception of the natural state of the oceans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roman, Joe -- Palumbi, Stephen R -- New York, N.Y. -- Science. 2003 Jul 25;301(5632):508-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Organismic and Evolutionary Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12881568" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Atlantic Ocean ; Base Sequence ; Conservation of Natural Resources ; DNA, Mitochondrial/genetics ; *Ecosystem ; Female ; Genetic Variation ; Genetics, Population ; Male ; Molecular Sequence Data ; Population Density ; Population Dynamics ; Time Factors ; *Whales/classification/genetics
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  • 22
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-03-01
    Description: Although curvature of biological surfaces has been considered from mathematical and biophysical perspectives, its molecular and developmental basis is unclear. We have studied the cin mutant of Antirrhinum, which has crinkly rather than flat leaves. Leaves of cin display excess growth in marginal regions, resulting in a gradual introduction of negative curvature during development. This reflects a change in the shape and the progression of a cell-cycle arrest front moving from the leaf tip toward the base. CIN encodes a TCP protein and is expressed downstream of the arrest front. We propose that CIN promotes zero curvature (flatness) by making cells more sensitive to an arrest signal, particularly in marginal regions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nath, Utpal -- Crawford, Brian C W -- Carpenter, Rosemary -- Coen, Enrico -- New York, N.Y. -- Science. 2003 Feb 28;299(5611):1404-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Developmental Biology, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12610308" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Antirrhinum/cytology/*genetics/*growth & development/metabolism ; Base Sequence ; Cell Cycle ; Cell Differentiation ; Cell Division ; Cell Size ; Cyclin D3 ; Cyclins/genetics/metabolism ; Gene Deletion ; *Gene Expression Regulation, Plant ; *Genes, Plant ; Histones/genetics/metabolism ; Molecular Sequence Data ; Mutagenesis, Insertional ; Mutation ; Plant Leaves/anatomy & histology/cytology/*growth & development/metabolism ; Plant Proteins/chemistry/genetics/metabolism ; Surface Properties ; Transcription Factors/chemistry/genetics/*metabolism
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  • 23
    Publication Date: 2003-01-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rajagopal, Jayaraj -- Anderson, William J -- Kume, Shoen -- Martinez, Olga I -- Melton, Douglas A -- New York, N.Y. -- Science. 2003 Jan 17;299(5605):363.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12532008" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies/immunology ; Apoptosis ; Cell Differentiation ; Cell Line ; Embryo, Mammalian/*cytology ; Humans ; Insulin/*analysis/genetics/immunology/*metabolism ; Islets of Langerhans/*cytology/metabolism ; Mice ; Microscopy, Confocal ; RNA, Messenger/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Stem Cells/*cytology/metabolism
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  • 24
    Publication Date: 2003-09-13
    Description: During spliceosome activation, a large structural rearrangement occurs that involves the release of two small nuclear RNAs, U1 and U4, and the addition of a protein complex associated with Prp19p. We show here that the Prp19p-associated complex is required for stable association of U5 and U6 with the spliceosome after U4 is dissociated. Ultraviolet crosslinking analysis revealed the existence of two modes of base pairing between U6 and the 5' splice site, as well as a switch of such base pairing from one to the other that required the Prp19p-associated complex during spliceosome activation. Moreover, a Prp19p-dependent structural change in U6 small nuclear ribonucleoprotein particles was detected that involves destabilization of Sm-like (Lsm) proteins to bring about interactions between the Lsm binding site of U6 and the intron sequence near the 5' splice site, indicating dynamic association of Lsm with U6 and a direct role of Lsm proteins in activation of the spliceosome.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chan, Shih-Peng -- Kao, Der-I -- Tsai, Wei-Yu -- Cheng, Soo-Chen -- New York, N.Y. -- Science. 2003 Oct 10;302(5643):279-82. Epub 2003 Sep 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Microbiology and Immunology, National Yang-Ming University, Shih-Pai, Taiwan, Republic of China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12970570" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Base Pairing ; Binding Sites ; Blotting, Northern ; Introns ; Molecular Sequence Data ; RNA Precursors/metabolism ; RNA Splicing ; RNA, Small Nuclear/metabolism ; RNA-Binding Proteins/chemistry/metabolism ; Ribonuclease H/metabolism ; Ribonucleoprotein, U4-U6 Small Nuclear/chemistry/*metabolism ; Saccharomyces cerevisiae Proteins/*metabolism ; Spliceosomes/*metabolism
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  • 25
    Publication Date: 2003-07-19
    Description: We collected and completely sequenced 28,469 full-length complementary DNA clones from Oryza sativa L. ssp. japonica cv. Nipponbare. Through homology searches of publicly available sequence data, we assigned tentative protein functions to 21,596 clones (75.86%). Mapping of the cDNA clones to genomic DNA revealed that there are 19,000 to 20,500 transcription units in the rice genome. Protein informatics analysis against the InterPro database revealed the existence of proteins presented in rice but not in Arabidopsis. Sixty-four percent of our cDNAs are homologous to Arabidopsis proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rice Full-Length cDNA Consortium -- National Institute of Agrobiological Sciences Rice Full-Length cDNA Project Team -- Kikuchi, Shoshi -- Satoh, Kouji -- Nagata, Toshifumi -- Kawagashira, Nobuyuki -- Doi, Koji -- Kishimoto, Naoki -- Yazaki, Junshi -- Ishikawa, Masahiro -- Yamada, Hitomi -- Ooka, Hisako -- Hotta, Isamu -- Kojima, Keiichi -- Namiki, Takahiro -- Ohneda, Eisuke -- Yahagi, Wataru -- Suzuki, Kohji -- Li, Chao Jie -- Ohtsuki, Kenji -- Shishiki, Toru -- Foundation of Advancement of International Science Genome Sequencing & Analysis Group -- Otomo, Yasuhiro -- Murakami, Kazuo -- Iida, Yoshiharu -- Sugano, Sumio -- Fujimura, Tatsuto -- Suzuki, Yutaka -- Tsunoda, Yuki -- Kurosaki, Takashi -- Kodama, Takeko -- Masuda, Hiromi -- Kobayashi, Michie -- Xie, Quihong -- Lu, Min -- Narikawa, Ryuya -- Sugiyama, Akio -- Mizuno, Kouichi -- Yokomizo, Satoko -- Niikura, Junko -- Ikeda, Rieko -- Ishibiki, Junya -- Kawamata, Midori -- Yoshimura, Akemi -- Miura, Junichirou -- Kusumegi, Takahiro -- Oka, Mitsuru -- Ryu, Risa -- Ueda, Mariko -- Matsubara, Kenichi -- RIKEN -- Kawai, Jun -- Carninci, Piero -- Adachi, Jun -- Aizawa, Katsunori -- Arakawa, Takahiro -- Fukuda, Shiro -- Hara, Ayako -- Hashizume, Wataru -- Hayatsu, Norihito -- Imotani, Koichi -- Ishii, Yoshiyuki -- Itoh, Masayoshi -- Kagawa, Ikuko -- Kondo, Shinji -- Konno, Hideaki -- Miyazaki, Ai -- Osato, Naoki -- Ota, Yoshimi -- Saito, Rintaro -- Sasaki, Daisuke -- Sato, Kenjiro -- Shibata, Kazuhiro -- Shinagawa, Akira -- Shiraki, Toshiyuki -- Yoshino, Masayasu -- Hayashizaki, Yoshihide -- Yasunishi, Ayako -- New York, N.Y. -- Science. 2003 Jul 18;301(5631):376-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, National Institute of Agrobiological Sciences, 2-1-2 Kannon-dai, Tsukuba, Ibaraki 305-8602, Japan. skikuchi@nias.affrc.go.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12869764" target="_blank"〉PubMed〈/a〉
    Keywords: Alternative Splicing ; Amino Acid Sequence ; Cloning, Molecular ; Computational Biology ; DNA, Complementary ; Databases, Nucleic Acid ; Databases, Protein ; Genes, Plant ; *Genome, Plant ; Molecular Sequence Data ; Open Reading Frames ; Oryza/*genetics ; Plant Proteins/chemistry/genetics/physiology ; Protein Structure, Tertiary ; RNA, Antisense/genetics ; *Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; Sequence Homology, Nucleic Acid ; Transcription Factors/chemistry/genetics ; Transcription, Genetic
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  • 26
    Publication Date: 2003-09-27
    Description: A survey of the dog genome sequence (6.22 million sequence reads; 1.5x coverage) demonstrates the power of sample sequencing for comparative analysis of mammalian genomes and the generation of species-specific resources. More than 650 million base pairs (〉25%) of dog sequence align uniquely to the human genome, including fragments of putative orthologs for 18,473 of 24,567 annotated human genes. Mutation rates, conserved synteny, repeat content, and phylogeny can be compared among human, mouse, and dog. A variety of polymorphic elements are identified that will be valuable for mapping the genetic basis of diseases and traits in the dog.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kirkness, Ewen F -- Bafna, Vineet -- Halpern, Aaron L -- Levy, Samuel -- Remington, Karin -- Rusch, Douglas B -- Delcher, Arthur L -- Pop, Mihai -- Wang, Wei -- Fraser, Claire M -- Venter, J Craig -- New York, N.Y. -- Science. 2003 Sep 26;301(5641):1898-903.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Institute for Genomic Research, Rockville, MD 20850, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14512627" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chromosomes, Mammalian/genetics ; Computational Biology ; Conserved Sequence ; Contig Mapping ; DNA, Intergenic ; Dogs/*genetics ; Genetic Variation ; *Genome ; Genome, Human ; Genomics ; Humans ; Long Interspersed Nucleotide Elements ; Male ; Mice/genetics ; Molecular Sequence Data ; Mutation ; Phylogeny ; Physical Chromosome Mapping ; Polymorphism, Single Nucleotide ; RNA, Messenger/genetics ; Repetitive Sequences, Nucleic Acid ; Sequence Alignment ; *Sequence Analysis, DNA ; Short Interspersed Nucleotide Elements ; Synteny
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  • 27
    Publication Date: 2003-08-09
    Description: Alternative pre-messenger RNA splicing is an important mechanism for generating protein diversity and may explain in part how mammalian complexity arises from a surprisingly small complement of genes. Here, we describe "digital polony exon profiling,"a single molecule-based technology for studying complex alternative pre-messenger RNA splicing. This technology allows researchers to monitor the combinatorial diversity of exon inclusion in individual transcripts. A minisequencing strategy provides single nucleotide resolution, and the digital nature of the technology allows quantitation of individual splicing variants. Digital polony exon profiling can be used to investigate the physiological and pathological roles of alternately spliced messenger RNAs, as well as the mechanisms by which these messenger RNAs are produced.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhu, Jun -- Shendure, Jay -- Mitra, Robi D -- Church, George M -- 5U54GM62119/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2003 Aug 8;301(5634):836-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12907803" target="_blank"〉PubMed〈/a〉
    Keywords: Acrylamide ; *Alternative Splicing ; Animals ; Antigens, CD44/genetics ; Brain/metabolism ; Cell Line ; Cell Line, Transformed ; Cyclic AMP Response Element-Binding Protein ; *Exons ; Humans ; Mice ; Microtubule-Associated Proteins/genetics ; Nerve Tissue Proteins/genetics ; Polymerase Chain Reaction/*methods ; Polymorphism, Single Nucleotide ; Protein Isoforms ; RNA Precursors/*genetics/metabolism ; RNA-Binding Proteins ; SMN Complex Proteins
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  • 28
    facet.materialart.
    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-03-28
    Description: The metabotropic glutamate receptors (mGluRs) are widely distributed in the brain and play important roles in synaptic plasticity. Here it is shown that some types of mGluRs are activated not only by glutamate but also by extracellular Ca2+ (Ca2+o). A single amino acid residue was found to determine the sensitivity of mGluRs to Ca2+o. One of the receptors, mGluR1alpha, but not its point mutant with reduced sensitivity to Ca2+o, caused morphological changes when transfected into mammalian cells. Thus, the sensing of Ca2+o by mGluRs may be important in cells under physiological condition.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kubo, Y -- Miyashita, T -- Murata, Y -- New York, N.Y. -- Science. 1998 Mar 13;279(5357):1722-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurophysiology, Tokyo Metropolitan Institute for Neuroscience, Musashidai 2-6, Fuchu, Tokyo 183-8526, Japan. ykubo@tmin.ac.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9497291" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/ultrastructure ; Amino Acid Sequence ; Animals ; Binding Sites ; Brain/metabolism ; CHO Cells ; Calcium/*metabolism/pharmacology ; Cell Size ; Cricetinae ; Cyclic AMP/metabolism ; G Protein-Coupled Inwardly-Rectifying Potassium Channels ; Glutamic Acid/metabolism/pharmacology ; Molecular Sequence Data ; Oocytes ; Point Mutation ; Potassium Channels/metabolism ; *Potassium Channels, Inwardly Rectifying ; Rats ; Receptors, Metabotropic Glutamate/chemistry/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Second Messenger Systems ; Transfection ; Xenopus laevis
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  • 29
    Publication Date: 1998-12-16
    Description: A peripheral membrane protein that is interactive with lymphocytic choriomeningitis virus (LCMV) was purified from cells permissive to infection. Tryptic peptides from this protein were determined to be alpha-dystroglycan (alpha-DG). Several strains of LCMV and other arenaviruses, including Lassa fever virus (LFV), Oliveros, and Mobala, bound to purified alpha-DG protein. Soluble alpha-DG blocked both LCMV and LFV infection. Cells bearing a null mutation of the gene encoding DG were resistant to LCMV infection, and reconstitution of DG expression in null mutant cells restored susceptibility to LCMV infection. Thus, alpha-DG is a cellular receptor for both LCMV and LFV.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cao, W -- Henry, M D -- Borrow, P -- Yamada, H -- Elder, J H -- Ravkov, E V -- Nichol, S T -- Compans, R W -- Campbell, K P -- Oldstone, M B -- AG 00080/AG/NIA NIH HHS/ -- AI 09484/AI/NIAID NIH HHS/ -- DK09712/DK/NIDDK NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1998 Dec 11;282(5396):2079-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9851928" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Arenavirus/metabolism ; Cell Line ; Cytoskeletal Proteins/chemistry/genetics/*metabolism ; Dystroglycans ; Lassa virus/*metabolism/physiology ; Lymphocytic choriomeningitis virus/*metabolism/physiology ; Membrane Glycoproteins/chemistry/genetics/*metabolism ; Mice ; Molecular Sequence Data ; Mutation ; Receptors, Virus/chemistry/*metabolism ; Recombinant Fusion Proteins/metabolism ; Virus Replication
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  • 30
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-04-29
    Description: After the vertebrate lens is induced from head ectoderm, lens-specific genes are expressed. Transcriptional regulation of the lens-specific alphaA-crystallin gene is controlled by an enhancer element, alphaCE2. A gene encoding an alphaCE2-binding protein, L-maf(lens-specific maf), was isolated. L-maf expression is initiated in the lens placode and is restricted to lens cells. The gene product L-Maf regulates the expression of multiple genes expressed in the lens, and ectopic expression of this transcription factor converts chick embryonic ectodermal cells and cultured cells into lens fibers. Thus, vertebrate lens induction and differentiation can be triggered by the activation of L-Maf.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ogino, H -- Yasuda, K -- New York, N.Y. -- Science. 1998 Apr 3;280(5360):115-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma 630-0101, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9525857" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Basic-Leucine Zipper Transcription Factors ; Cell Differentiation ; Cells, Cultured ; Chick Embryo ; Crystallins/genetics ; DNA, Complementary ; DNA-Binding Proteins/chemistry/genetics ; Ectoderm ; Enhancer Elements, Genetic ; Eye Proteins/genetics ; G-Box Binding Factors ; *Gene Expression Regulation, Developmental ; Genes, Reporter ; Intermediate Filament Proteins/genetics ; Lens, Crystalline/*cytology/*embryology/metabolism ; Maf Transcription Factors ; Molecular Sequence Data ; Promoter Regions, Genetic ; Recombinant Fusion Proteins/metabolism ; Transcription Factors/chemistry/genetics/*metabolism ; *Transcription, Genetic ; Transcriptional Activation ; Transfection
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  • 31
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-02-07
    Description: The Son of Sevenless (Sos) proteins control receptor-mediated activation of Ras by catalyzing the exchange of guanosine diphosphate for guanosine triphosphate on Ras. The NH2-terminal region of Sos contains a Dbl homology (DH) domain in tandem with a pleckstrin homology (PH) domain. In COS-1 cells, the DH domain of Sos stimulated guanine nucleotide exchange on Rac but not Cdc42 in vitro and in vivo. The tandem DH-PH domain of Sos (DH-PH-Sos) was defective in Rac activation but regained Rac stimulating activity when it was coexpressed with activated Ras. Ras-mediated activation of DH-PH-Sos did not require activation of mitogen-activated protein kinase but it was dependent on activation of phosphoinositide 3-kinase. These results reveal a potential mechanism for coupling of Ras and Rac signaling pathways.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nimnual, A S -- Yatsula, B A -- Bar-Sagi, D -- CA09176/CA/NCI NIH HHS/ -- CA28146/CA/NCI NIH HHS/ -- CA55360/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1998 Jan 23;279(5350):560-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics and Microbiology, State University of New York at Stony Brook, Stony Brook, NY 11794, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9438849" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/metabolism ; Animals ; COS Cells ; Calcium-Calmodulin-Dependent Protein Kinases/metabolism ; Cell Cycle Proteins/metabolism ; Cell Line ; Cell Membrane/ultrastructure ; Enzyme Activation ; GTP Phosphohydrolases/*metabolism ; GTP-Binding Proteins/*metabolism ; Guanine Nucleotide Exchange Factors ; Guanosine Diphosphate/metabolism ; Guanosine Triphosphate/metabolism ; Humans ; JNK Mitogen-Activated Protein Kinases ; Membrane Proteins/chemistry/*metabolism ; *Mitogen-Activated Protein Kinases ; Proteins/metabolism ; Proto-Oncogene Proteins ; Recombinant Fusion Proteins/metabolism ; Retroviridae Proteins, Oncogenic/chemistry ; Signal Transduction ; Son of Sevenless Proteins ; Transfection ; cdc42 GTP-Binding Protein ; rac GTP-Binding Proteins ; ras Guanine Nucleotide Exchange Factors ; ras Proteins/*metabolism
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  • 32
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-08-28
    Description: Control of the activation of apoptosis is important both in development and in protection against cancer. In the classic genetic model Caenorhabditis elegans, the pro-apoptotic protein CED-4 activates the CED-3 caspase and is inhibited by the Bcl-2-like protein CED-9. Both processes are mediated by protein-protein interaction. Facilitating the proximity of CED-3 zymogen molecules was found to induce caspase activation and cell death. CED-4 protein oligomerized in cells and in vitro. This oligomerization induced CED-3 proximity and competed with CED-4:CED-9 interaction. Mutations that abolished CED-4 oligomerization inactivated its ability to activate CED-3. Thus, the mechanism of control is that CED-3 in CED-3:CED-4 complexes is activated by CED-4 oligomerization, which is inhibited by binding of CED-9 to CED-4.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, X -- Chang, H Y -- Baltimore, D -- CA51462/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1998 Aug 28;281(5381):1355-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9721101" target="_blank"〉PubMed〈/a〉
    Keywords: *Apoptosis ; Apoptosis Regulatory Proteins ; Biopolymers ; *Caenorhabditis elegans Proteins ; Calcium-Binding Proteins/*chemistry/genetics/*metabolism ; *Caspases ; Cell Line ; Chemistry, Physical ; Cysteine Endopeptidases/*metabolism ; Cysteine Proteinase Inhibitors/pharmacology ; Enzyme Activation ; Enzyme Precursors/metabolism ; HeLa Cells ; Helminth Proteins/*chemistry/genetics/*metabolism ; Humans ; Mutation ; Oligopeptides/pharmacology ; Physicochemical Phenomena ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Recombinant Fusion Proteins/metabolism ; Tacrolimus/pharmacology ; Transfection ; bcl-X Protein
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  • 33
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-03-21
    Description: Mice homozygous for a disrupted allele of the mismatch repair gene Pms2 have a mutator phenotype. When this allele is crossed into quasi-monoclonal (QM) mice, which have a very limited B cell repertoire, homozygotes have fewer somatic mutations at the immunoglobulin heavy chain and lambda chain loci than do heterozygotes or wild-type QM mice. That is, mismatch repair seems to contribute to somatic hypermutation rather than stifling it. It is suggested that at immunoglobulin loci in hypermutable B cells, mismatched base pairs are "corrected" according to the newly synthesized DNA strand, thereby fixing incipient mutations instead of eliminating them.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cascalho, M -- Wong, J -- Steinberg, C -- Wabl, M -- 1R01 GM37699/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1998 Feb 20;279(5354):1207-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, University of California, San Francisco, CA 94143-0670, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9469811" target="_blank"〉PubMed〈/a〉
    Keywords: *Adenosine Triphosphatases ; Alleles ; Amino Acid Sequence ; Animals ; B-Lymphocytes/immunology ; Base Composition ; Base Sequence ; Cloning, Molecular ; Crosses, Genetic ; *DNA Repair ; *DNA Repair Enzymes ; *DNA-Binding Proteins ; Female ; Gene Rearrangement ; *Genes, Immunoglobulin ; Heterozygote ; Immunoglobulin Heavy Chains/chemistry/genetics ; Immunoglobulin Variable Region/chemistry/*genetics ; Immunoglobulin lambda-Chains/chemistry/genetics ; Male ; Mice ; Mice, Knockout ; Molecular Sequence Data ; *Mutation ; Proteins/*genetics/physiology
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  • 34
    Publication Date: 1998-12-05
    Description: Group I introns possess a single active site that catalyzes the two sequential reactions of self-splicing. An RNA comprising the two domains of the Tetrahymena thermophila group I intron catalytic core retains activity, and the 5.0 angstrom crystal structure of this 247-nucleotide ribozyme is now described. Close packing of the two domains forms a shallow cleft capable of binding the short helix that contains the 5' splice site. The helix that provides the binding site for the guanosine substrate deviates significantly from A-form geometry, providing a tight binding pocket. The binding pockets for both the 5' splice site helix and guanosine are formed and oriented in the absence of these substrates. Thus, this large ribozyme is largely preorganized for catalysis, much like a globular protein enzyme.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Golden, B L -- Gooding, A R -- Podell, E R -- Cech, T R -- New York, N.Y. -- Science. 1998 Oct 9;282(5387):259-64.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309-0215, USA. bgolden@petunia.colorado.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9841391" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Pairing ; Base Sequence ; Binding Sites ; Catalysis ; Crystallography, X-Ray ; Guanosine/metabolism ; Introns ; Magnesium/metabolism ; Manganese/metabolism ; *Models, Molecular ; Molecular Sequence Data ; *Nucleic Acid Conformation ; Phosphates/metabolism ; RNA Splicing ; RNA, Catalytic/*chemistry/metabolism ; Tetrahymena thermophila/*genetics
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  • 35
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-07-10
    Description: The 2.5 angstrom resolution x-ray crystal structure of the Escherichia coli RNA polymerase (RNAP) alpha subunit amino-terminal domain (alphaNTD), which is necessary and sufficient to dimerize and assemble the other RNAP subunits into a transcriptionally active enzyme and contains all of the sequence elements conserved among eukaryotic alpha homologs, has been determined. The alphaNTD monomer comprises two distinct, flexibly linked domains, only one of which participates in the dimer interface. In the alphaNTD dimer, a pair of helices from one monomer interact with the cognate helices of the other to form an extensive hydrophobic core. All of the determinants for interactions with the other RNAP subunits lie on one face of the alphaNTD dimer. Sequence alignments, combined with secondary-structure predictions, support proposals that a heterodimer of the eukaryotic RNAP subunits related to Saccharomyces cerevisiae Rpb3 and Rpb11 plays the role of the alphaNTD dimer in prokaryotic RNAP.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, G -- Darst, S A -- GM19441-01/GM/NIGMS NIH HHS/ -- GM53759/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1998 Jul 10;281(5374):262-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9657722" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Crystallography, X-Ray ; DNA-Directed RNA Polymerases/*chemistry ; Dimerization ; Escherichia coli/*enzymology ; Models, Molecular ; Molecular Sequence Data ; *Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; RNA Polymerase II/chemistry ; *Saccharomyces cerevisiae Proteins ; Sequence Alignment
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  • 36
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-02-07
    Description: The development of plant root systems is sensitive to the availability and distribution of nutrients within the soil. For example, lateral roots proliferate preferentially within nitrate (NO3-)-rich soil patches. A NO3--inducible Arabidopsis gene (ANR1), was identified that encodes a member of the MADS box family of transcription factors. Transgenic plants in which ANR1 was repressed had an altered sensitivity to NO3- and no longer responded to NO3--rich zones by lateral root proliferation, indicating that ANR1 is a key determinant of developmental plasticity in Arabidopsis roots.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, H -- Forde, B G -- New York, N.Y. -- Science. 1998 Jan 16;279(5349):407-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biochemistry and Physiology Department, IACR-Rothamsted, Harpenden, Herts AL5 2JQ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9430595" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/*genetics/growth & development/metabolism ; *Arabidopsis Proteins ; DNA-Binding Proteins/*genetics/physiology ; Gene Expression Regulation, Plant ; *Genes, Plant ; MADS Domain Proteins ; Molecular Sequence Data ; Nitrates/metabolism/*pharmacology ; Plant Proteins/*genetics/physiology ; Plant Roots/genetics/*growth & development/metabolism ; Plants, Genetically Modified ; Transcription Factors/*genetics/physiology
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  • 37
    Publication Date: 1998-12-18
    Description: CTLA-4, a negative regulator of T cell function, was found to associate with the T cell receptor (TCR) complex zeta chain in primary T cells. The association of TCRzeta with CTLA-4, reconstituted in 293 transfectants, was enhanced by p56(lck)-induced tyrosine phosphorylation. Coexpression of the CTLA-4-associated tyrosine phosphatase, SHP-2, resulted in dephosphorylation of TCRzeta bound to CTLA-4 and abolished the p56(lck)-inducible TCRzeta-CTLA-4 interaction. Thus, CTLA-4 inhibits TCR signal transduction by binding to TCRzeta and inhibiting tyrosine phosphorylation after T cell activation. These findings have broad implications for the negative regulation of T cell function and T cell tolerance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, K M -- Chuang, E -- Griffin, M -- Khattri, R -- Hong, D K -- Zhang, W -- Straus, D -- Samelson, L E -- Thompson, C B -- Bluestone, J A -- P01 AI35294-6/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1998 Dec 18;282(5397):2263-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ben May Institute for Cancer Research, and Committee on Immunology, University of Chicago, Chicago, IL 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9856951" target="_blank"〉PubMed〈/a〉
    Keywords: Abatacept ; Animals ; Antigens, CD ; Antigens, Differentiation/*metabolism ; CTLA-4 Antigen ; Cell Line ; Cells, Cultured ; Humans ; *Immunoconjugates ; Intracellular Signaling Peptides and Proteins ; *Lymphocyte Activation ; Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/genetics/metabolism ; Membrane Proteins/*metabolism ; Mice ; Mice, Inbred BALB C ; Models, Immunological ; Phosphorylation ; Phosphotyrosine/metabolism ; Protein Tyrosine Phosphatase, Non-Receptor Type 11 ; Protein Tyrosine Phosphatase, Non-Receptor Type 6 ; Protein Tyrosine Phosphatases/genetics/metabolism ; Receptors, Antigen, T-Cell/*metabolism ; Recombinant Fusion Proteins/metabolism ; SH2 Domain-Containing Protein Tyrosine Phosphatases ; *Signal Transduction ; T-Lymphocytes/*immunology ; Transfection ; src Homology Domains
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  • 38
    Publication Date: 1998-02-21
    Description: CREB binding protein (CBP) functions as an essential coactivator of transcription factors that are inhibited by the adenovirus early gene product E1A. Transcriptional activation by the signal transducer and activator of transcription-1 (STAT1) protein requires the C/H3 domain in CBP, which is the primary target of E1A inhibition. Here it was found that the C/H3 domain is not required for retinoic acid receptor (RAR) function, nor is it involved in E1A inhibition. Instead, E1A inhibits RAR function by preventing the assembly of CBP-nuclear receptor coactivator complexes, revealing differences in required CBP domains for transcriptional activation by RAR and STAT1.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kurokawa, R -- Kalafus, D -- Ogliastro, M H -- Kioussi, C -- Xu, L -- Torchia, J -- Rosenfeld, M G -- Glass, C K -- New York, N.Y. -- Science. 1998 Jan 30;279(5351):700-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Cellular and Molecular Medicine, Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0651, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9445474" target="_blank"〉PubMed〈/a〉
    Keywords: Adenovirus E1A Proteins/*metabolism/pharmacology ; Animals ; Binding Sites ; CREB-Binding Protein ; Cell Differentiation ; Cell Line ; DNA-Binding Proteins/metabolism ; Histone Acetyltransferases ; Humans ; Mutation ; Nuclear Proteins/chemistry/genetics/*metabolism ; Nuclear Receptor Coactivator 1 ; Nuclear Receptor Coactivator 3 ; Protein Binding ; Receptors, Retinoic Acid/metabolism ; Recombinant Fusion Proteins/metabolism ; STAT1 Transcription Factor ; Trans-Activators/metabolism ; Transcription Factors/chemistry/genetics/*metabolism ; *Transcription, Genetic ; Transcriptional Activation ; Tretinoin/pharmacology
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  • 39
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-08-07
    Description: The red clover necrotic mosaic virus genome is composed of two single-stranded RNA components, RNA-1 and RNA-2. The viral capsid protein is translated from a subgenomic RNA (sgRNA) that is transcribed from genomic RNA-1. Here, a 34-nucleotide sequence in RNA-2 is shown to be required for transcription of sgRNA. Mutations that prevent base-pairing between the RNA-1 subgenomic promoter and the 34-nucleotide trans-activator prevent expression of a reporter gene. A model is proposed in which direct binding of RNA-2 to RNA-1 trans-activates sgRNA synthesis. This RNA-mediated regulation of transcription is unusual among RNA viruses, which typically rely on protein regulators.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sit, T L -- Vaewhongs, A A -- Lommel, S A -- New York, N.Y. -- Science. 1998 Aug 7;281(5378):829-32.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Pathology, North Carolina State University, Raleigh, NC 27695-7616, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9694655" target="_blank"〉PubMed〈/a〉
    Keywords: Base Composition ; Base Sequence ; DNA, Complementary ; Gene Expression ; Genes, Reporter ; Green Fluorescent Proteins ; Luminescent Proteins/genetics ; Models, Genetic ; Molecular Sequence Data ; Mosaic Viruses/*genetics ; Mutation ; Nucleic Acid Conformation ; Promoter Regions, Genetic ; RNA, Double-Stranded/genetics/metabolism ; RNA, Messenger/biosynthesis/genetics ; RNA, Viral/biosynthesis/chemistry/*genetics ; Sequence Alignment ; *Transcriptional Activation
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  • 40
    Publication Date: 1998-02-21
    Description: Protein kinase B (PKB) is activated in response to phosphoinositide 3-kinases and their lipid products phosphatidylinositol 3,4, 5-trisphosphate [PtdIns(3,4,5)P3] and PtdIns(3,4)P2 in the signaling pathways used by a wide variety of growth factors, antigens, and inflammatory stimuli. PKB is a direct target of these lipids, but this regulation is complex. The lipids can bind to the pleckstrin homologous domain of PKB, causing its translocation to the membrane, and also enable upstream, Thr308-directed kinases to phosphorylate and activate PKB. Four isoforms of these PKB kinases were purified from sheep brain. They bound PtdIns(3,4,5)P3 and associated with lipid vesicles containing it. These kinases contain an NH2-terminal catalytic domain and a COOH-terminal pleckstrin homologous domain, and their heterologous expression augments receptor activation of PKB, which suggests they are the primary signal transducers that enable PtdIns(3,4,5)P3 or PtdIns- (3,4)P2 to activate PKB and hence to control signaling pathways regulating cell survival, glucose uptake, and glycogen metabolism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stephens, L -- Anderson, K -- Stokoe, D -- Erdjument-Bromage, H -- Painter, G F -- Holmes, A B -- Gaffney, P R -- Reese, C B -- McCormick, F -- Tempst, P -- Coadwell, J -- Hawkins, P T -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 1998 Jan 30;279(5351):710-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Inositide Laboratory, The Babraham Institute, Babraham, Cambridge CB2 4AT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9445477" target="_blank"〉PubMed〈/a〉
    Keywords: 3-Phosphoinositide-Dependent Protein Kinases ; Alternative Splicing ; Amino Acid Sequence ; Animals ; Cell Line ; Cell Membrane/enzymology ; Cloning, Molecular ; DNA, Complementary ; Drosophila ; Drosophila Proteins ; Enzyme Activation ; Humans ; Liposomes/metabolism ; Molecular Sequence Data ; Open Reading Frames ; Phosphatidylinositol Phosphates/*metabolism ; Phosphorylation ; Platelet-Derived Growth Factor/pharmacology ; Protein-Serine-Threonine Kinases/chemistry/genetics/isolation & ; purification/*metabolism ; Proto-Oncogene Proteins/*metabolism ; Proto-Oncogene Proteins c-akt ; Rats ; Recombinant Proteins/metabolism ; Sheep ; *Signal Transduction
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  • 41
    Publication Date: 1998-08-14
    Description: The timing and localization of DNA replication initiation in mammalian cells are heritable traits, but it is not known whether initiation requires specific DNA sequences. A site-specific recombination strategy was used to show that DNA sequences previously identified as replication initiation sites could initiate replication when transferred to new chromosomal locations. An 8-kilobase DNA sequence encompassing the origin of DNA replication in the human beta-globin locus initiated replication in the simian genome. Specific deletions within the globin origin did not initiate replication in these chromosomal sites. These data suggest that initiation of DNA replication in mammalian cells requires specific sequence information and extend the replicon hypothesis to higher eukaryotes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aladjem, M I -- Rodewald, L W -- Kolman, J L -- Wahl, G M -- CA48405/CA/NCI NIH HHS/ -- GM51104/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1998 Aug 14;281(5379):1005-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gene Expression Laboratory, The Salk Institute, San Diego, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9703500" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cercopithecus aethiops ; DNA/genetics ; DNA Nucleotidyltransferases/metabolism ; *DNA Replication ; Gene Targeting ; Globins/*genetics ; Humans ; Integrases/metabolism ; Polymerase Chain Reaction ; *Replication Origin ; S Phase ; Sequence Deletion ; *Viral Proteins
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  • 42
    Publication Date: 1998-08-28
    Description: A large protein complex mediates the phosphorylation of the inhibitor of kappaB (IkappaB), which results in the activation of nuclear factor kappaB (NF-kappaB). Two subunits of this complex, IkappaB kinase alpha (IKKalpha) and IkappaB kinase beta (IKKbeta), are required for NF-kappaB activation. Purified recombinant IKKalpha and IKKbeta expressed in insect cells were used to demonstrate that each protein can directly phosphorylate IkappaB proteins. IKKalpha and IKKbeta were found to form both homodimers and heterodimers. Both IKKalpha and IKKbeta phosphorylated IkappaB bound to NF-kappaB more efficiently than they phosphorylated free IkappaB. This result explains how free IkappaB can accumulate in cells in which IKK is still active and thus can contribute to the termination of NF-kappaB activation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zandi, E -- Chen, Y -- Karin, M -- AI 43477/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1998 Aug 28;281(5381):1360-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9721103" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Dimerization ; Enzyme Activation ; HeLa Cells ; Helix-Loop-Helix Motifs ; Humans ; I-kappa B Kinase ; Leucine Zippers ; Mutation ; NF-kappa B/antagonists & inhibitors/*metabolism ; Phosphorylation ; Protein-Serine-Threonine Kinases/chemistry/genetics/*metabolism ; Proto-Oncogene Proteins/*metabolism ; Recombinant Fusion Proteins/metabolism ; Recombinant Proteins/metabolism ; Spodoptera ; Transcription Factor RelB ; *Transcription Factors
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 43
    Publication Date: 1998-08-14
    Description: The breast and ovarian cancer susceptibility gene BRCA1 encodes a zinc finger protein of unknown function. Association of the BRCA1 protein with the DNA repair protein Rad51 and changes in the phosphorylation and cellular localization of the protein after exposure to DNA-damaging agents are consistent with a role for BRCA1 in DNA repair. Here, it is shown that mouse embryonic stem cells deficient in BRCA1 are defective in the ability to carry out transcription-coupled repair of oxidative DNA damage, and are hypersensitive to ionizing radiation and hydrogen peroxide. These results suggest that BRCA1 participates, directly or indirectly, in transcription-coupled repair of oxidative DNA damage.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gowen, L C -- Avrutskaya, A V -- Latour, A M -- Koller, B H -- Leadon, S A -- CA40453/CA/NCI NIH HHS/ -- CA70490/CA/NCI NIH HHS/ -- IP50CA58223/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1998 Aug 14;281(5379):1009-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Curriculum in Genetics and Molecular Biology and Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9703501" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; BRCA1 Protein/genetics/*physiology ; Cell Line ; DNA Damage ; *DNA Repair ; Hydrogen Peroxide ; Mice ; Oxidation-Reduction ; Stem Cells ; Thymine/analogs & derivatives/immunology/metabolism ; Transcription, Genetic ; Ultraviolet Rays
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  • 44
    Publication Date: 1998-03-21
    Description: Viral infection is sometimes associated with the initiation or exacerbation of autoimmune disease, although the underlying mechanisms remain unclear. One proposed mechanism is that viral determinants that mimic host antigens trigger self-reactive T cell clones to destroy host tissue. An epitope expressed by a coat protein of herpes simplex virus-type 1 (HSV-1) KOS strain has now been shown to be recognized by autoreactive T cells that target corneal antigens in a murine model of autoimmune herpes stromal keratitis. Mutant HSV-1 viruses that lacked this epitope did not induce autoimmune disease. Thus, expression of molecular mimics can influence the development of autoimmune disease after viral infection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhao, Z S -- Granucci, F -- Yeh, L -- Schaffer, P A -- Cantor, H -- AI 37562/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1998 Feb 27;279(5355):1344-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Harvard Medical School, and Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9478893" target="_blank"〉PubMed〈/a〉
    Keywords: Adoptive Transfer ; Amino Acid Sequence ; Animals ; Autoantigens/immunology ; Autoimmune Diseases/*immunology ; CD4-Positive T-Lymphocytes/immunology ; Capsid/chemistry/genetics/*immunology ; *Capsid Proteins ; Cornea/*immunology ; Epitopes ; Eye Proteins/immunology ; Herpesvirus 1, Human/*immunology ; Keratitis, Herpetic/*immunology ; Lymphocyte Activation ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Mice, SCID ; *Molecular Mimicry ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Oligopeptides/immunology ; Viral Proteins
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  • 45
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-03-28
    Description: The OxyR transcription factor is sensitive to oxidation and activates the expression of antioxidant genes in response to hydrogen peroxide in Escherichia coli. Genetic and biochemical studies revealed that OxyR is activated through the formation of a disulfide bond and is deactivated by enzymatic reduction with glutaredoxin 1 (Grx1). The gene encoding Grx1 is regulated by OxyR, thus providing a mechanism for autoregulation. The redox potential of OxyR was determined to be -185 millivolts, ensuring that OxyR is reduced in the absence of stress. These results represent an example of redox signaling through disulfide bond formation and reduction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zheng, M -- Aslund, F -- Storz, G -- New York, N.Y. -- Science. 1998 Mar 13;279(5357):1718-21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9497290" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Bacterial Proteins/genetics/metabolism ; Base Sequence ; Cysteine/metabolism ; *DNA-Binding Proteins ; Disulfides/*metabolism ; Escherichia coli/genetics/*metabolism ; Escherichia coli Proteins ; Gene Expression Regulation, Bacterial ; Glutaredoxins ; Glutathione/metabolism ; Glutathione Disulfide/metabolism ; Glutathione Reductase/metabolism ; Hydrogen Peroxide/*metabolism/pharmacology ; Molecular Sequence Data ; Oxidation-Reduction ; Oxidative Stress ; *Oxidoreductases ; Proteins/genetics/metabolism ; Repressor Proteins/genetics/*metabolism ; Signal Transduction ; Thioredoxins/metabolism ; Transcription Factors/genetics/*metabolism
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  • 46
    Publication Date: 1998-11-30
    Description: The NPH1 gene of Arabidopsis thaliana encodes a 120-kilodalton serine-threonine protein kinase hypothesized to function as a photoreceptor for phototropism. When expressed in insect cells, the NPH1 protein is phosphorylated in response to blue light irradiation. The biochemical and photochemical properties of the photosensitive protein reflect those of the native protein in microsomal membranes. Recombinant NPH1 noncovalently binds flavin mononucleotide, a likely chromophore for light-dependent autophosphorylation. The fluorescence excitation spectrum of the recombinant protein is similar to the action spectrum for phototropism, consistent with the conclusion that NPH1 is an autophosphorylating flavoprotein photoreceptor mediating phototropic responses in higher plants.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Christie, J M -- Reymond, P -- Powell, G K -- Bernasconi, P -- Raibekas, A A -- Liscum, E -- Briggs, W R -- New York, N.Y. -- Science. 1998 Nov 27;282(5394):1698-701.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Biology, Carnegie Institution of Washington, 260 Panama Street, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9831559" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arabidopsis/genetics/*physiology ; *Arabidopsis Proteins ; Cell Line ; Cryptochromes ; *Drosophila Proteins ; *Eye Proteins ; Flavin Mononucleotide/metabolism ; Flavoproteins/physiology ; Genes, Plant ; Light ; Mutation ; Phosphoproteins/genetics/*metabolism ; Phosphorylation ; *Photoreceptor Cells, Invertebrate ; *Phototropism ; Protein-Serine-Threonine Kinases/genetics/*metabolism ; Receptors, G-Protein-Coupled ; Recombinant Proteins/metabolism ; Spectrometry, Fluorescence ; Spodoptera ; Transfection
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  • 47
    Publication Date: 1998-10-23
    Description: Analysis of the 1,042,519-base pair Chlamydia trachomatis genome revealed unexpected features related to the complex biology of chlamydiae. Although chlamydiae lack many biosynthetic capabilities, they retain functions for performing key steps and interconversions of metabolites obtained from their mammalian host cells. Numerous potential virulence-associated proteins also were characterized. Several eukaryotic chromatin-associated domain proteins were identified, suggesting a eukaryotic-like mechanism for chlamydial nucleoid condensation and decondensation. The phylogenetic mosaic of chlamydial genes, including a large number of genes with phylogenetic origins from eukaryotes, implies a complex evolution for adaptation to obligate intracellular parasitism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stephens, R S -- Kalman, S -- Lammel, C -- Fan, J -- Marathe, R -- Aravind, L -- Mitchell, W -- Olinger, L -- Tatusov, R L -- Zhao, Q -- Koonin, E V -- Davis, R W -- AI 39258/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1998 Oct 23;282(5389):754-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Infectious Diseases, University of California, Berkeley, CA 94720, USA. ctgenome@socrates.berkeley.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9784136" target="_blank"〉PubMed〈/a〉
    Keywords: Aerobiosis ; Amino Acid Sequence ; Amino Acids/biosynthesis ; Bacterial Outer Membrane Proteins/genetics ; Bacterial Proteins/chemistry/genetics ; Biological Evolution ; Chlamydia trachomatis/classification/*genetics/metabolism/physiology ; DNA Repair ; Energy Metabolism ; Enzymes/chemistry/genetics ; *Genome, Bacterial ; Humans ; Lipids/biosynthesis ; Molecular Sequence Data ; Peptidoglycan/biosynthesis/genetics ; Phylogeny ; Protein Biosynthesis ; Recombination, Genetic ; *Sequence Analysis, DNA ; Transcription, Genetic ; Transformation, Bacterial ; Virulence
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  • 48
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-07-10
    Description: Recombinant proteins containing four cysteines at the i, i + 1, i + 4, and i + 5 positions of an alpha helix were fluorescently labeled in living cells by extracellular administration of 4',5'-bis(1,3, 2-dithioarsolan-2-yl)fluorescein. This designed small ligand is membrane-permeant and nonfluorescent until it binds with high affinity and specificity to the tetracysteine domain. Such in situ labeling adds much less mass than does green fluorescent protein and offers greater versatility in attachment sites as well as potential spectroscopic and chemical properties. This system provides a recipe for slightly modifying a target protein so that it can be singled out from the many other proteins inside live cells and fluorescently stained by small nonfluorescent dye molecules added from outside the cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Griffin, B A -- Adams, S R -- Tsien, R Y -- NS27177/NS/NINDS NIH HHS/ -- T32 CA09523/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1998 Jul 10;281(5374):269-72.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093-0647, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9657724" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Calmodulin/chemistry/genetics/metabolism ; Cell Membrane Permeability ; Cell Survival ; Cysteine/*chemistry ; Energy Transfer ; Ethylene Glycol ; Fluoresceins/chemical synthesis/chemistry/*metabolism ; Fluorescence ; *Fluorescent Dyes ; Green Fluorescent Proteins ; HeLa Cells ; Humans ; Jurkat Cells ; Ligands ; Luminescent Proteins/chemistry/genetics/metabolism ; Molecular Sequence Data ; Organometallic Compounds/chemical synthesis/chemistry/*metabolism ; Peptides/chemistry/*metabolism ; Protein Structure, Secondary ; Recombinant Proteins/chemistry/*metabolism ; Spectrometry, Fluorescence ; Transfection
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  • 49
    Publication Date: 1998-01-24
    Description: Gene expression was visualized in single living mammalian cells with beta-lactamase as a reporter that hydrolyzes a substrate loaded intracellularly as a membrane-permeant ester. Each enzyme molecule changed the fluorescence of many substrate molecules from green to blue by disrupting resonance energy transfer. This wavelength shift was detectable by eye or color film in individual cells containing less than 100 beta-lactamase molecules. The robust change in emission ratio reveals quantitative heterogeneity in real-time gene expression, enables clonal selection by flow cytometry, and forms a basis for high-throughput screening of pharmaceutical candidate drugs in living mammalian cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zlokarnik, G -- Negulescu, P A -- Knapp, T E -- Mere, L -- Burres, N -- Feng, L -- Whitney, M -- Roemer, K -- Tsien, R Y -- NS27177/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1998 Jan 2;279(5347):84-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Aurora Biosciences, 11010 Torreyana Road, San Diego, CA 92121, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9417030" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cell Separation/methods ; Clone Cells/*metabolism ; DNA-Binding Proteins/genetics/metabolism ; Drug Evaluation, Preclinical ; Energy Transfer ; Flow Cytometry ; Fluoresceins/metabolism ; Fluorescent Dyes/metabolism ; *Gene Expression ; *Genes, Reporter ; Half-Life ; Humans ; *Lactams ; Muscarinic Agonists/pharmacology ; Muscarinic Antagonists/pharmacology ; NFATC Transcription Factors ; *Nuclear Proteins ; Sensitivity and Specificity ; Spectrometry, Fluorescence ; Transcription Factors/genetics/metabolism ; *Transcription, Genetic ; Transfection ; Tumor Cells, Cultured ; Umbelliferones/metabolism ; beta-Lactamases/*genetics/metabolism ; beta-Lactams/metabolism
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  • 50
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-03-21
    Description: The three-dimensional structure of a 70-kilodalton amino terminally truncated form of human topoisomerase I in complex with a 22-base pair duplex oligonucleotide, determined to a resolution of 2.8 angstroms, reveals all of the structural elements of the enzyme that contact DNA. The linker region that connects the central core of the enzyme to the carboxyl-terminal domain assumes a coiled-coil configuration and protrudes away from the remainder of the enzyme. The positively charged DNA-proximal surface of the linker makes only a few contacts with the DNA downstream of the cleavage site. In combination with the crystal structures of the reconstituted human topoisomerase I before and after DNA cleavage, this information suggests which amino acid residues are involved in catalyzing phosphodiester bond breakage and religation. The structures also lead to the proposal that the topoisomerization step occurs by a mechanism termed "controlled rotation."〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stewart, L -- Redinbo, M R -- Qiu, X -- Hol, W G -- Champoux, J J -- CA65656/CA/NCI NIH HHS/ -- GM16713/GM/NIGMS NIH HHS/ -- GM49156/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1998 Mar 6;279(5356):1534-41.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biomolecular Structure Center and Department of Biological Structure, School of Medicine, University of Washington, Seattle, WA 98195-7742, USA. emerald_biostructures@rocketmail.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9488652" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arginine/chemistry/metabolism ; Binding Sites ; Catalysis ; Crystallography, X-Ray ; DNA/chemistry/*metabolism ; DNA Topoisomerases, Type I/*chemistry/*metabolism ; Humans ; Hydrogen Bonding ; *Models, Chemical ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; Oligodeoxyribonucleotides/chemistry/metabolism ; *Protein Conformation ; Protein Structure, Secondary ; Tyrosine/chemistry/metabolism
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  • 51
    Publication Date: 1998-11-13
    Description: The ectodomains of numerous proteins are released from cells by proteolysis to yield soluble intercellular regulators. The responsible protease, tumor necrosis factor-alpha converting enzyme (TACE), has been identified only in the case when tumor necrosis factor-alpha (TNFalpha) is released. Analyses of cells lacking this metalloproteinase-disintegrin revealed an expanded role for TACE in the processing of other cell surface proteins, including a TNF receptor, the L-selectin adhesion molecule, and transforming growth factor-alpha (TGFalpha). The phenotype of mice lacking TACE suggests an essential role for soluble TGFalpha in normal development and emphasizes the importance of protein ectodomain shedding in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Peschon, J J -- Slack, J L -- Reddy, P -- Stocking, K L -- Sunnarborg, S W -- Lee, D C -- Russell, W E -- Castner, B J -- Johnson, R S -- Fitzner, J N -- Boyce, R W -- Nelson, N -- Kozlosky, C J -- Wolfson, M F -- Rauch, C T -- Cerretti, D P -- Paxton, R J -- March, C J -- Black, R A -- CA43793/CA/NCI NIH HHS/ -- DK53804/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1998 Nov 13;282(5392):1281-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Immunex Corporation, Seattle, WA 98101, USA. peschon@immunex.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9812885" target="_blank"〉PubMed〈/a〉
    Keywords: ADAM Proteins ; Amino Acid Sequence ; Animals ; Catalytic Domain ; Cell Membrane/*metabolism ; Cells, Cultured ; Crosses, Genetic ; *Embryonic and Fetal Development ; L-Selectin/metabolism ; Ligands ; Membrane Proteins/*metabolism ; Metalloendopeptidases/chemistry/genetics/*metabolism ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Mutation ; Phenotype ; Protein Processing, Post-Translational ; Receptors, Tumor Necrosis Factor/metabolism ; Transforming Growth Factor alpha/metabolism ; Tumor Necrosis Factor-alpha/*metabolism
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  • 52
    Publication Date: 1998-03-21
    Description: Long-term potentiation (LTP) is an activity-dependent strengthening of synaptic efficacy that is considered to be a model of learning and memory. Protein tyrosine phosphorylation is necessary to induce LTP. Here, induction of LTP in CA1 pyramidal cells of rats was prevented by blocking the tyrosine kinase Src, and Src activity was increased by stimulation producing LTP. Directly activating Src in the postsynaptic neuron enhanced excitatory synaptic responses, occluding LTP. Src-induced enhancement of alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) receptor-mediated synaptic responses required raised intracellular Ca2+ and N-methyl-D-aspartate (NMDA) receptors. Thus, Src activation is necessary and sufficient for inducing LTP and may function by up-regulating NMDA receptors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lu, Y M -- Roder, J C -- Davidow, J -- Salter, M W -- New York, N.Y. -- Science. 1998 Feb 27;279(5355):1363-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Samuel Lunenfeld Research Institute, Mount Sinai Hospital, and Department of Molecular and Medical Genetics, University of Toronto, M5S 1A8, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9478899" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Calcium/metabolism ; Electric Stimulation ; Enzyme Activation ; Excitatory Postsynaptic Potentials/drug effects ; Hippocampus/cytology/enzymology/*physiology ; In Vitro Techniques ; *Long-Term Potentiation ; Molecular Sequence Data ; Oligopeptides/pharmacology ; Patch-Clamp Techniques ; Peptide Fragments/pharmacology ; Proto-Oncogene Proteins pp60(c-src)/pharmacology ; Pyramidal Cells/enzymology/*physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, AMPA/physiology ; Receptors, N-Methyl-D-Aspartate/physiology ; Recombinant Proteins/pharmacology ; Up-Regulation ; src-Family Kinases/*metabolism
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  • 53
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-04-16
    Description: Genetic selection was exploited in combination with structure-based design to transform an intimately entwined, dimeric chorismate mutase into a monomeric, four-helix-bundle protein with near native activity. Successful reengineering depended on choosing a thermostable starting protein, introducing point mutations that preferentially destabilize the wild-type dimer, and using directed evolution to optimize an inserted interhelical turn. Contrary to expectations based on studies of other four-helix-bundle proteins, only a small fraction of possible turn sequences (fewer than 0.05 percent) yielded well-behaved, monomeric, and highly active enzymes. Selection for catalytic function thus provides an efficient yet stringent method for rapidly assessing correctly folded polypeptides and may prove generally useful for protein design.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉MacBeath, G -- Kast, P -- Hilvert, D -- New York, N.Y. -- Science. 1998 Mar 20;279(5358):1958-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Scripps Research Institute, Department of Chemistry, 10550 North Torrey Pines Road, La Jolla, California, 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9506949" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Catalysis ; Chorismate Mutase/*chemistry/genetics/*metabolism ; Circular Dichroism ; Cloning, Molecular ; Dimerization ; *Directed Molecular Evolution ; Escherichia coli/genetics ; Models, Molecular ; Molecular Sequence Data ; *Protein Conformation ; *Protein Engineering ; Protein Folding ; Protein Structure, Secondary ; Recombinant Proteins/chemistry/metabolism ; Transformation, Bacterial
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  • 54
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-07-31
    Description: Gamete interactions during fertilization exhibit species specificity. In abalone, the sperm protein lysin species-specifically creates a hole in the egg envelope. Lysin evolves rapidly by positive Darwinian selection. Evolution of the egg receptor for lysin provides the selective pressure for lysin's divergence. The egg receptor for lysin is a tandemly repeated sequence that evolves by concerted evolution. Concerted evolution in the egg receptor could explain the rapid, adaptive evolution in sperm lysin and may provide an underlying molecular mechanism that gives rise to species-specific fertilization.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Swanson, W J -- Vacquier, V D -- HD12986/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 1998 Jul 31;281(5377):710-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, La Jolla, CA 92093-0202, USA. jwswanson@ucsd.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9685267" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Egg Proteins/chemistry/*genetics/metabolism ; *Evolution, Molecular ; Female ; Introns ; Male ; Molecular Sequence Data ; Mollusca/chemistry/*genetics/physiology ; Mucoproteins/chemistry/genetics/*metabolism ; Ovum/chemistry/physiology ; Receptors, Cell Surface/chemistry/*genetics/metabolism ; Repetitive Sequences, Nucleic Acid ; Selection, Genetic ; Sequence Alignment ; Species Specificity ; Sperm-Ovum Interactions ; Spermatozoa/chemistry/physiology ; Vitelline Membrane/*chemistry/metabolism
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  • 55
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-04-09
    Description: A "switch" mutant of the Arc repressor homodimer was constructed by interchanging the sequence positions of a hydrophobic core residue, leucine 12, and an adjacent surface polar residue, asparagine 11, in each strand of an intersubunit beta sheet. The mutant protein adopts a fold in which each beta strand is replaced by a right-handed helix and side chains in this region undergo significant repacking. The observed structural changes allow the protein to maintain solvent exposure of polar side chains and optimal burial of hydrophobic side chains. These results suggest that new protein folds can evolve from existing folds without drastic or large-scale mutagenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cordes, M H -- Walsh, N P -- McKnight, C J -- Sauer, R T -- AI-15706/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1999 Apr 9;284(5412):325-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10195898" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Asparagine/chemistry ; Circular Dichroism ; Hydrogen Bonding ; Leucine/chemistry ; Models, Molecular ; Molecular Sequence Data ; Mutagenesis, Insertional ; Nuclear Magnetic Resonance, Biomolecular ; Protein Conformation ; *Protein Folding ; *Protein Structure, Secondary ; Protein Structure, Tertiary ; Repressor Proteins/*chemistry ; Viral Proteins/*chemistry ; Viral Regulatory and Accessory Proteins
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  • 56
    Publication Date: 1999-09-25
    Description: The flow of information from calcium-mobilizing receptors to nuclear factor of activated T cells (NFAT)-dependent genes is critically dependent on interaction between the phosphatase calcineurin and the transcription factor NFAT. A high-affinity calcineurin-binding peptide was selected from combinatorial peptide libraries based on the calcineurin docking motif of NFAT. This peptide potently inhibited NFAT activation and NFAT-dependent expression of endogenous cytokine genes in T cells, without affecting the expression of other cytokines that require calcineurin but not NFAT. Substitution of the optimized peptide sequence into the natural calcineurin docking site increased the calcineurin responsiveness of NFAT. Compounds that interfere selectively with the calcineurin-NFAT interaction without affecting calcineurin phosphatase activity may be useful as therapeutic agents that are less toxic than current drugs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aramburu, J -- Yaffe, M B -- Lopez-Rodriguez, C -- Cantley, L C -- Hogan, P G -- Rao, A -- R01 AI 40127/AI/NIAID NIH HHS/ -- R01 GM056203/GM/NIGMS NIH HHS/ -- R01 HL 03601/HL/NHLBI NIH HHS/ -- R43 AI 43726/AI/NIAID NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1999 Sep 24;285(5436):2129-33.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10497131" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Calcineurin/*metabolism ; Calcineurin Inhibitors ; Cell Nucleus/metabolism ; Cyclosporine/pharmacology ; Cytokines/biosynthesis/genetics ; DNA-Binding Proteins/*antagonists & inhibitors/chemistry/metabolism ; Gene Expression Regulation ; Genes, Reporter ; HeLa Cells ; Humans ; Immunosuppressive Agents/chemistry/metabolism/*pharmacology ; Jurkat Cells ; Molecular Sequence Data ; NFATC Transcription Factors ; *Nuclear Proteins ; Oligopeptides/chemistry/metabolism/*pharmacology ; Peptide Library ; Peptides/chemistry/metabolism/*pharmacology ; Phosphorylation ; Recombinant Fusion Proteins/metabolism ; T-Lymphocytes/*drug effects/immunology ; Transcription Factors/*antagonists & inhibitors/chemistry/metabolism ; Transfection
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  • 57
    Publication Date: 1999-11-05
    Description: The Brca1 (breast cancer gene 1) tumor suppressor protein is phosphorylated in response to DNA damage. Results from this study indicate that the checkpoint protein kinase ATM (mutated in ataxia telangiectasia) was required for phosphorylation of Brca1 in response to ionizing radiation. ATM resides in a complex with Brca1 and phosphorylated Brca1 in vivo and in vitro in a region that contains clusters of serine-glutamine residues. Phosphorylation of this domain appears to be functionally important because a mutated Brca1 protein lacking two phosphorylation sites failed to rescue the radiation hypersensitivity of a Brca1-deficient cell line. Thus, phosphorylation of Brca1 by the checkpoint kinase ATM may be critical for proper responses to DNA double-strand breaks and may provide a molecular explanation for the role of ATM in breast cancer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cortez, D -- Wang, Y -- Qin, J -- Elledge, S J -- GM44664/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1999 Nov 5;286(5442):1162-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Verna and Mars McLean Department of Biochemistry and Molecular Biology, Howard Hughes Medical Institute, Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10550055" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Ataxia Telangiectasia/genetics ; Ataxia Telangiectasia Mutated Proteins ; BRCA1 Protein/*metabolism ; Breast Neoplasms/genetics ; Cell Cycle Proteins ; Cell Line ; *DNA Damage ; *DNA Repair ; DNA, Complementary ; DNA-Binding Proteins ; Female ; Gamma Rays ; Genes, BRCA1 ; Genetic Predisposition to Disease ; HeLa Cells ; Heterozygote ; Humans ; Molecular Sequence Data ; Mutation ; Phosphorylation ; Protein-Serine-Threonine Kinases/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Tumor Suppressor Proteins
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  • 58
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-10-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sherley, J L -- New York, N.Y. -- Science. 1999 Sep 10;285(5434):1676-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10523183" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; *Gene Expression Regulation ; Genetic Vectors ; Operator Regions, Genetic ; Recombinant Fusion Proteins/metabolism ; Repressor Proteins/metabolism ; *Research Design ; Tetracycline/*pharmacology ; Trans-Activators/metabolism
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  • 59
    Publication Date: 1999-10-03
    Description: Precursors of alpha-defensin peptides require activation for bactericidal activity. In mouse small intestine, matrilysin colocalized with alpha-defensins (cryptdins) in Paneth cell granules, and in vitro it cleaved the pro segment from cryptdin precursors. Matrilysin-deficient (MAT-/-) mice lacked mature cryptdins and accumulated precursor molecules. Intestinal peptide preparations from MAT-/- mice had decreased antimicrobial activity. Orally administered bacteria survived in greater numbers and were more virulent in MAT-/- mice than in MAT+/+ mice. Thus, matrilysin functions in intestinal mucosal defense by regulating the activity of defensins, which may be a common role for this metalloproteinase in its numerous epithelial sites of expression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilson, C L -- Ouellette, A J -- Satchell, D P -- Ayabe, T -- Lopez-Boado, Y S -- Stratman, J L -- Hultgren, S J -- Matrisian, L M -- Parks, W C -- New York, N.Y. -- Science. 1999 Oct 1;286(5437):113-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatrics, Division of Allergy and Pulmonary Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. wilson_c@kids.wustl.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10506557" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Catalysis ; Cytoplasmic Granules/enzymology ; Escherichia coli/growth & development ; Escherichia coli Infections/immunology/microbiology ; Female ; Humans ; *Immunity, Innate ; *Immunity, Mucosal ; Intestinal Mucosa/enzymology/immunology/microbiology ; Intestine, Small/enzymology/*immunology/microbiology ; Male ; Matrix Metalloproteinase 7 ; Metalloendopeptidases/genetics/*metabolism ; Mice ; Molecular Sequence Data ; Paneth Cells/enzymology ; Protein Precursors/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Salmonella typhimurium/growth & development/pathogenicity ; Tissue Extracts/pharmacology
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  • 60
    Publication Date: 1999-09-18
    Description: The antifungal defense of Drosophila is controlled by the spaetzle/Toll/cactus gene cassette. Here, a loss-of-function mutation in the gene encoding a blood serine protease inhibitor, Spn43Ac, was shown to lead to constitutive expression of the antifungal peptide drosomycin, and this effect was mediated by the spaetzle and Toll gene products. Spaetzle was cleaved by proteolytic enzymes to its active ligand form shortly after immune challenge, and cleaved Spaetzle was constitutively present in Spn43Ac-deficient flies. Hence, Spn43Ac negatively regulates the Toll signaling pathway, and Toll does not function as a pattern recognition receptor in the Drosophila host defense.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Levashina, E A -- Langley, E -- Green, C -- Gubb, D -- Ashburner, M -- Hoffmann, J A -- Reichhart, J M -- New York, N.Y. -- Science. 1999 Sep 17;285(5435):1917-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉UPR 9022 CNRS, Institut de Biologie Moleculaire et Cellulaire, 15 Rue Rene Descartes, Strasbourg 67084, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10489372" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antifungal Agents/*metabolism ; *Antimicrobial Cationic Peptides ; Body Patterning ; Drosophila/embryology/genetics/*immunology ; *Drosophila Proteins ; Escherichia coli/genetics/immunology ; Genes, Insect ; Hemolymph/metabolism ; Insect Proteins/*biosynthesis/genetics/metabolism/*physiology ; Membrane Glycoproteins/genetics/*physiology ; Micrococcus luteus/immunology ; Molecular Sequence Data ; Mutagenesis ; Peptides/genetics/metabolism ; *Receptors, Cell Surface ; Recombinant Fusion Proteins/genetics/metabolism ; Serine Proteinase Inhibitors/genetics/*metabolism ; Serpins/genetics/*metabolism ; Signal Transduction ; Toll-Like Receptors ; Up-Regulation
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  • 61
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-10-26
    Description: Katanin, a member of the AAA adenosine triphosphatase (ATPase) superfamily, uses nucleotide hydrolysis energy to sever and disassemble microtubules. Many AAA enzymes disassemble stable protein-protein complexes, but their mechanisms are not well understood. A fluorescence resonance energy transfer assay demonstrated that the p60 subunit of katanin oligomerized in an adenosine triphosphate (ATP)- and microtubule-dependent manner. Oligomerization increased the affinity of katanin for microtubules and stimulated its ATPase activity. After hydrolysis of ATP, microtubule-bound katanin oligomers disassembled microtubules and then dissociated into free katanin monomers. Coupling a nucleotide-dependent oligomerization cycle to the disassembly of a target protein complex may be a general feature of ATP-hydrolyzing AAA domains.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hartman, J J -- Vale, R D -- New York, N.Y. -- Science. 1999 Oct 22;286(5440):782-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Howard Hughes Medical Institute and the Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10531065" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/*chemistry/*metabolism ; Adenosine Triphosphate/analogs & derivatives/*metabolism ; Amino Acid Sequence ; Centrifugation, Density Gradient ; Fluorescence ; Hydrolysis ; Luminescent Proteins ; Microtubules/*metabolism ; Models, Biological ; Molecular Sequence Data ; Polymers ; Recombinant Fusion Proteins/chemistry/metabolism ; Tubulin/metabolism
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  • 62
    Publication Date: 1999-08-28
    Description: Class II transactivator (CIITA) is a global transcriptional coactivator of human leukocyte antigen-D (HLA-D) genes. CIITA contains motifs similar to guanosine triphosphate (GTP)-binding proteins. This report shows that CIITA binds GTP, and mutations in these motifs decrease its GTP-binding and transactivation activity. Substitution of these motifs with analogous sequences from Ras restores CIITA function. CIITA exhibits little GTPase activity, yet mutations in CIITA that confer GTPase activity reduce transcriptional activity. GTP binding by CIITA correlates with nuclear import. Thus, unlike other GTP-binding proteins, CIITA is involved in transcriptional activation that uses GTP binding to facilitate its own nuclear import.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Harton, J A -- Cressman, D E -- Chin, K C -- Der, C J -- Ting, J P -- AI29564/AI/NIAID NIH HHS/ -- AI41751/AI/NIAID NIH HHS/ -- AI45580/AI/NIAID NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1999 Aug 27;285(5432):1402-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lineberger Comprehensive Cancer Center, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10464099" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Animals ; Binding Sites ; COS Cells ; Cell Line ; Cell Nucleus/*metabolism ; GTP-Binding Proteins/chemistry/genetics/*metabolism ; *Genes, MHC Class II ; Guanosine Triphosphate/*metabolism ; HLA-DR Antigens/genetics ; Humans ; Mutation ; *Nuclear Proteins ; Promoter Regions, Genetic ; Temperature ; Trans-Activators/chemistry/genetics/*metabolism ; Transcription Factors/metabolism ; *Transcriptional Activation
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  • 63
    Publication Date: 1999-01-23
    Description: The plant hormone abscisic acid (ABA) regulates potassium and chloride ion channels at the plasma membrane of guard cells, leading to stomatal closure that reduces transpirational water loss from the leaf. The tobacco Nt-SYR1 gene encodes a syntaxin that is associated with the plasma membrane. Syntaxins and related SNARE proteins aid intracellular vesicle trafficking, fusion, and secretion. Disrupting Nt-Syr1 function by cleavage with Clostridium botulinum type C toxin or competition with a soluble fragment of Nt-Syr1 prevents potassium and chloride ion channel response to ABA in guard cells and implicates Nt-Syr1 in an ABA-signaling cascade.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leyman, B -- Geelen, D -- Quintero, F J -- Blatt, M R -- New York, N.Y. -- Science. 1999 Jan 22;283(5401):537-40.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Plant Physiology and Biophysics, University of London, Wye College, Wye, Kent TN25 5AH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9915701" target="_blank"〉PubMed〈/a〉
    Keywords: Abscisic Acid/*pharmacology ; Amino Acid Sequence ; Animals ; Botulinum Toxins/metabolism ; Cell Membrane/physiology ; Chloride Channels/*physiology ; Genes, Plant ; Genetic Complementation Test ; Ion Channel Gating/drug effects ; Membrane Proteins/chemistry/genetics/*physiology ; Molecular Sequence Data ; Oocytes ; Patch-Clamp Techniques ; Plant Growth Regulators/*pharmacology ; Plant Leaves/*physiology ; *Plants, Toxic ; Potassium Channels/*physiology ; Qa-SNARE Proteins ; Saccharomyces cerevisiae/genetics/growth & development ; Signal Transduction ; Tobacco/genetics/*physiology ; Xenopus
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  • 64
    Publication Date: 1999-11-05
    Description: Glutamatergic neurotransmission is controlled by presynaptic metabotropic glutamate receptors (mGluRs). A subdomain in the intracellular carboxyl-terminal tail of group III mGluRs binds calmodulin and heterotrimeric guanosine triphosphate-binding protein (G protein) betagamma subunits in a mutually exclusive manner. Mutations interfering with calmodulin binding and calmodulin antagonists inhibit G protein-mediated modulation of ionic currents by mGluR 7. Calmodulin antagonists also prevent inhibition of excitatory neurotransmission via presynaptic mGluRs. These results reveal a novel mechanism of presynaptic modulation in which Ca(2+)-calmodulin is required to release G protein betagamma subunits from the C-tail of group III mGluRs in order to mediate glutamatergic autoinhibition.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉O'Connor, V -- El Far, O -- Bofill-Cardona, E -- Nanoff, C -- Freissmuth, M -- Karschin, A -- Airas, J M -- Betz, H -- Boehm, S -- New York, N.Y. -- Science. 1999 Nov 5;286(5442):1180-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurochemistry, Max Planck Institute for Brain Research, Deutschordenstrasse 46, 60528 Frankfurt, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10550060" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Calcium/metabolism ; Calmodulin/antagonists & inhibitors/*metabolism ; Cells, Cultured ; Dimerization ; G Protein-Coupled Inwardly-Rectifying Potassium Channels ; GTP-Binding Proteins/*metabolism ; Glutamic Acid/*metabolism ; Hippocampus/cytology/metabolism ; Humans ; Mice ; Molecular Sequence Data ; Neurons/metabolism ; Potassium Channels/metabolism ; *Potassium Channels, Inwardly Rectifying ; Presynaptic Terminals/metabolism ; Propionates/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Metabotropic Glutamate/antagonists & inhibitors/*metabolism ; Recombinant Fusion Proteins/metabolism ; Sesterterpenes ; Signal Transduction ; Swine ; *Synaptic Transmission ; Terpenes/pharmacology
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  • 65
    Publication Date: 1999-02-26
    Description: Chlamydia infections are epidemiologically linked to human heart disease. A peptide from the murine heart muscle-specific alpha myosin heavy chain that has sequence homology to the 60-kilodalton cysteine-rich outer membrane proteins of Chlamydia pneumoniae, C. psittaci, and C. trachomatis was shown to induce autoimmune inflammatory heart disease in mice. Injection of the homologous Chlamydia peptides into mice also induced perivascular inflammation, fibrotic changes, and blood vessel occlusion in the heart, as well as triggering T and B cell reactivity to the homologous endogenous heart muscle-specific peptide. Chlamydia DNA functioned as an adjuvant in the triggering of peptide-induced inflammatory heart disease. Infection with C. trachomatis led to the production of autoantibodies to heart muscle-specific epitopes. Thus, Chlamydia-mediated heart disease is induced by antigenic mimicry of a heart muscle-specific protein.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bachmaier, K -- Neu, N -- de la Maza, L M -- Pal, S -- Hessel, A -- Penninger, J M -- New York, N.Y. -- Science. 1999 Feb 26;283(5406):1335-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Amgen Institute, Ontario Cancer Institute, Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, Ontario M5G 2C1, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10037605" target="_blank"〉PubMed〈/a〉
    Keywords: Adoptive Transfer ; Amino Acid Sequence ; Animals ; Antigens, Bacterial/chemistry/immunology ; Autoantibodies/biosynthesis ; Autoimmune Diseases/immunology/*microbiology/pathology ; B-Lymphocytes/immunology ; Bacterial Outer Membrane Proteins/chemistry/*immunology ; CD4-Positive T-Lymphocytes/immunology ; Chlamydia/*immunology ; Chlamydia Infections/complications/*immunology ; Chlamydia trachomatis/immunology ; CpG Islands ; Humans ; Immunization ; Lymphocyte Activation ; Mice ; Mice, Inbred BALB C ; *Molecular Mimicry ; Molecular Sequence Data ; Myocarditis/immunology/*microbiology/pathology ; Myocardium/immunology/pathology ; Myosin Heavy Chains/chemistry/*immunology ; Oligodeoxyribonucleotides/immunology ; Sequence Homology, Amino Acid
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  • 66
    Publication Date: 1999-03-26
    Description: The carboxyl-terminal domain of colicin E5 was shown to inhibit protein synthesis of Escherichia coli. Its target, as revealed through in vivo and in vitro experiments, was not ribosomes as in the case of E3, but the transfer RNAs (tRNAs) for Tyr, His, Asn, and Asp, which contain a modified base, queuine, at the wobble position of each anticodon. The E5 carboxyl-terminal domain hydrolyzed these tRNAs just on the 3' side of this nucleotide. Tight correlation was observed between the toxicity of E5 and the cleavage of intracellular tRNAs of this group, implying that these tRNAs are the primary targets of colicin E5.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ogawa, T -- Tomita, K -- Ueda, T -- Watanabe, K -- Uozumi, T -- Masaki, H -- New York, N.Y. -- Science. 1999 Mar 26;283(5410):2097-100.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biotechnology, Graduate School of Agricultural and Life Sciences, University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10092236" target="_blank"〉PubMed〈/a〉
    Keywords: Anticodon/*metabolism ; Bacterial Proteins/biosynthesis/genetics/pharmacology ; Base Sequence ; Cloning, Molecular ; Colicins/genetics/*metabolism/pharmacology ; Escherichia coli/drug effects/metabolism ; *Escherichia coli Proteins ; Guanine/analogs & derivatives/analysis ; Molecular Sequence Data ; RNA, Bacterial/chemistry/*metabolism ; RNA, Ribosomal, 16S/metabolism ; RNA, Transfer, Amino Acid-Specific/chemistry/*metabolism ; RNA, Transfer, Asn/chemistry/metabolism ; RNA, Transfer, Asp/chemistry/metabolism ; RNA, Transfer, His/chemistry/metabolism ; RNA, Transfer, Tyr/chemistry/metabolism ; Ribonucleases/genetics/*metabolism/pharmacology ; Ribosomes/metabolism
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  • 67
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-02-19
    Description: A single kinesin molecule can move "processively" along a microtubule for more than 1 micrometer before detaching from it. The prevailing explanation for this processive movement is the "walking model," which envisions that each of two motor domains (heads) of the kinesin molecule binds coordinately to the microtubule. This implies that each kinesin molecule must have two heads to "walk" and that a single-headed kinesin could not move processively. Here, a motor-domain construct of KIF1A, a single-headed kinesin superfamily protein, was shown to move processively along the microtubule for more than 1 micrometer. The movement along the microtubules was stochastic and fitted a biased Brownian-movement model.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Okada, Y -- Hirokawa, N -- New York, N.Y. -- Science. 1999 Feb 19;283(5405):1152-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, Hongo, Tokyo 113-0033, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10024239" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Amino Acid Sequence ; Animals ; Catalytic Domain ; Diffusion ; Drosophila ; Kinesin/chemistry/*metabolism ; Kinetics ; Microscopy, Fluorescence ; Microtubules/*metabolism ; Models, Chemical ; Molecular Motor Proteins/chemistry/*metabolism ; Molecular Sequence Data ; Nerve Tissue Proteins/chemistry/*metabolism ; Recombinant Fusion Proteins ; Stochastic Processes ; Thermodynamics
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  • 68
    Publication Date: 1999-07-31
    Description: Many immune receptors are composed of separate ligand-binding and signal-transducing subunits. In natural killer (NK) and T cells, DAP10 was identified as a cell surface adaptor protein in an activating receptor complex with NKG2D, a receptor for the stress-inducible and tumor-associated major histocompatibility complex molecule MICA. Within the DAP10 cytoplasmic domain, an Src homology 2 (SH2) domain-binding site was capable of recruiting the p85 subunit of the phosphatidylinositol 3-kinase (PI 3-kinase), providing for NKG2D-dependent signal transduction. Thus, NKG2D-DAP10 receptor complexes may activate NK and T cell responses against MICA-bearing tumors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, J -- Song, Y -- Bakker, A B -- Bauer, S -- Spies, T -- Lanier, L L -- Phillips, J H -- AI30581/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1999 Jul 30;285(5428):730-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉DNAX Research Institute, 901 California Avenue, Palo Alto, CA 94304, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10426994" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Cell Line ; Cytotoxicity, Immunologic ; Humans ; Killer Cells, Natural/*immunology/metabolism ; Ligands ; *Lymphocyte Activation ; Membrane Proteins/chemistry/genetics/*metabolism ; Mice ; Molecular Sequence Data ; NK Cell Lectin-Like Receptor Subfamily K ; Neoplasms/immunology ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphorylation ; Phosphotyrosine/metabolism ; Receptors, Immunologic/chemistry/genetics/*metabolism ; Receptors, Natural Killer Cell ; Signal Transduction ; T-Lymphocytes/*immunology/metabolism ; Tumor Cells, Cultured ; src Homology Domains
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  • 69
    Publication Date: 1999-04-09
    Description: Phosphorylation of inhibitor of kappa B (IkappaB) proteins is an important step in the activation of the transcription nuclear factor kappa B (NF-kappaB) and requires two IkappaB kinases, IKK1 (IKKalpha) and IKK2 (IKKbeta). Mice that are devoid of the IKK2 gene had extensive liver damage from apoptosis and died as embryos, but these mice could be rescued by the inactivation of the gene encoding tumor necrosis factor receptor 1. Mouse embryonic fibroblast cells that were isolated from IKK2-/- embryos showed a marked reduction in tumor necrosis factor-alpha (TNF-alpha)- and interleukin-1alpha-induced NF-kappaB activity and an enhanced apoptosis in response to TNF-alpha. IKK1 associated with NF-kappaB essential modulator (IKKgamma/IKKAP1), another component of the IKK complex. These results show that IKK2 is essential for mouse development and cannot be substituted with IKK1.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Q -- Van Antwerp, D -- Mercurio, F -- Lee, K F -- Verma, I M -- New York, N.Y. -- Science. 1999 Apr 9;284(5412):321-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Salk Institute, La Jolla, CA 92037, USA. Signal Pharmaceuticals, San Diego, CA 92121, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10195897" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Cell Line ; DNA-Binding Proteins/metabolism ; Embryonic and Fetal Development ; Gene Targeting ; I-kappa B Kinase ; I-kappa B Proteins ; Interleukin-1/pharmacology ; Liver/cytology/*embryology ; Mice ; NF-kappa B/metabolism ; Phosphorylation ; Polymerase Chain Reaction ; Protein-Serine-Threonine Kinases/genetics/*metabolism ; Receptors, Tumor Necrosis Factor/genetics/metabolism ; Recombinant Fusion Proteins/metabolism ; Sequence Deletion ; Signal Transduction ; Transcription Factor RelA ; Transcription Factors/metabolism ; Tumor Necrosis Factor-alpha/pharmacology
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  • 70
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-01-29
    Description: The protein encoded by the c-MYC proto-oncogene is a transcription factor that can both activate and repress the expression of target genes, but few of its transcriptional targets have been identified. Here, c-MYC is shown to repress the expression of the heavy subunit of the protein ferritin (H-ferritin), which sequesters intracellular iron, and to stimulate the expression of the iron regulatory protein-2 (IRP2), which increases the intracellular iron pool. Down-regulation of the expression of H-ferritin gene was required for cell transformation by c-MYC. These results indicate that c-MYC coordinately regulates genes controlling intracellular iron concentrations and that this function is essential for the control of cell proliferation and transformation by c-MYC.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, K J -- Polack, A -- Dalla-Favera, R -- CA-37165/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1999 Jan 29;283(5402):676-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Oncology, Department of Pathology, Columbia University, New York, NY 10032, USA. an.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9924025" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Division ; Cell Line ; Cell Line, Transformed ; Cell Transformation, Neoplastic ; DNA/biosynthesis ; Down-Regulation ; Ferritins/*genetics/metabolism ; *Gene Expression Regulation ; Genes, myc ; Homeostasis ; Iron/*metabolism ; Iron Regulatory Protein 2 ; Iron-Regulatory Proteins ; Iron-Sulfur Proteins/*genetics/metabolism ; Proto-Oncogene Proteins c-myc/*physiology ; RNA/metabolism ; RNA-Binding Proteins/*genetics/metabolism ; Receptors, Transferrin/genetics ; Transcription, Genetic ; Transfection
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  • 71
    Publication Date: 1999-09-18
    Description: Antithrombin, a member of the serpin family, functions as an inhibitor of thrombin and other enzymes. Cleavage of the carboxyl-terminal loop of antithrombin induces a conformational change in the molecule. Here it is shown that the cleaved conformation of antithrombin has potent antiangiogenic and antitumor activity in mouse models. The latent form of intact antithrombin, which is similar in conformation to the cleaved molecule, also inhibited angiogenesis and tumor growth. These data provide further evidence that the clotting and fibrinolytic pathways are directly involved in the regulation of angiogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉O'Reilly, M S -- Pirie-Shepherd, S -- Lane, W S -- Folkman, J -- P01-CA45548/CA/NCI NIH HHS/ -- R01-CA64481/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1999 Sep 17;285(5435):1926-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Surgery, Children's Hospital, Departments of Surgery and Cellular Biology, Harvard Microchemistry Facility, 16 Divinity Avenue, Cambridge, MA 02138, USA. oreilly@hub.tch.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10489375" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antineoplastic Agents/chemistry/isolation & purification/metabolism/*pharmacology ; Antithrombins/chemistry/isolation & purification/metabolism/*pharmacology ; Carcinoma, Small Cell/blood supply/drug therapy ; Cell Line ; Culture Media, Conditioned ; Drug Screening Assays, Antitumor ; Humans ; Lung Neoplasms/blood supply/drug therapy ; Mice ; Mice, SCID ; Neoplasm Transplantation ; Neovascularization, Pathologic/*drug therapy ; Peptide Fragments/chemistry/metabolism/pharmacology ; Protein Conformation ; Tumor Cells, Cultured
    Print ISSN: 0036-8075
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  • 72
    Publication Date: 1999-09-18
    Description: The bacterial pathogen Yersinia uses a type III secretion system to inject several virulence factors into target cells. One of the Yersinia virulence factors, YopJ, was shown to bind directly to the superfamily of MAPK (mitogen-activated protein kinase) kinases (MKKs) blocking both phosphorylation and subsequent activation of the MKKs. These results explain the diverse activities of YopJ in inhibiting the extracellular signal-regulated kinase, c-Jun amino-terminal kinase, p38, and nuclear factor kappa B signaling pathways, preventing cytokine synthesis and promoting apoptosis. YopJ-related proteins that are found in a number of bacterial pathogens of animals and plants may function to block MKKs so that host signaling responses can be modulated upon infection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Orth, K -- Palmer, L E -- Bao, Z Q -- Stewart, S -- Rudolph, A E -- Bliska, J B -- Dixon, J E -- 18024/PHS HHS/ -- AI35175/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1999 Sep 17;285(5435):1920-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109-0606, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10489373" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*physiology ; Calcium-Calmodulin-Dependent Protein Kinases/*antagonists & inhibitors ; Cell Line ; Enzyme Activation ; Enzyme Inhibitors/*pharmacology ; HeLa Cells ; Humans ; *MAP Kinase Kinase Kinase 1 ; NF-kappa B/metabolism ; Phosphorylation ; Protein Binding ; Protein-Serine-Threonine Kinases/genetics/metabolism ; Recombinant Fusion Proteins/genetics/metabolism ; Transfection ; Virulence ; Yersinia pseudotuberculosis/genetics/metabolism/pathogenicity/*physiology
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  • 73
    Publication Date: 2000-01-05
    Description: Phytochromes are a family of photoreceptors used by green plants to entrain their development to the light environment. The distribution of these chromoproteins has been expanded beyond photoautotrophs with the discovery of phytochrome-like proteins in the nonphotosynthetic eubacteria Deinococcus radiodurans and Pseudomonas aeruginosa. Like plant phytochromes, the D. radiodurans receptor covalently binds linear tetrapyrroles autocatalytically to generate a photochromic holoprotein. However, the attachment site is distinct, using a histidine to potentially form a Schiff base linkage. Sequence homology and mutational analysis suggest that D. radiodurans bacteriophytochrome functions as a light-regulated histidine kinase, which helps protect the bacterium from visible light.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Davis, S J -- Vener, A V -- Vierstra, R D -- New York, N.Y. -- Science. 1999 Dec 24;286(5449):2517-20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Genetics, Cellular and Molecular Biology Program and Department of Horticulture, University of Wisconsin-Madison, 1575 Linden Drive, Madison, WI 53706, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10617469" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Bacterial Proteins/chemistry/genetics/*metabolism ; Biliverdine/analogs & derivatives/metabolism ; Binding Sites ; Gram-Positive Cocci/genetics/*metabolism ; Histidine/metabolism ; Light ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Photoreceptors, Microbial/chemistry/genetics/*metabolism ; Phytochrome/metabolism ; Protein Kinases/chemistry/genetics/*metabolism ; Pseudomonas aeruginosa/*metabolism ; Signal Transduction
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  • 74
    Publication Date: 1999-06-12
    Description: In many organisms, master control genes coordinately regulate sex-specific aspects of development. SDC-2 was shown to induce hermaphrodite sexual differentiation and activate X chromosome dosage compensation in Caenorhabditis elegans. To control these distinct processes, SDC-2 acts as a strong gene-specific repressor and a weaker chromosome-wide repressor. To initiate hermaphrodite development, SDC-2 associates with the promoter of the male sex-determining gene her-1 to repress its transcription. To activate dosage compensation, SDC-2 triggers assembly of a specialized protein complex exclusively on hermaphrodite X chromosomes to reduce gene expression by half. SDC-2 can localize to X chromosomes without other components of the dosage compensation complex, suggesting that SDC-2 targets dosage compensation machinery to X chromosomes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dawes, H E -- Berlin, D S -- Lapidus, D M -- Nusbaum, C -- Davis, T L -- Meyer, B J -- GM30702/GM/NIGMS NIH HHS/ -- T32 GM07127/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1999 Jun 11;284(5421):1800-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3204, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10364546" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caenorhabditis elegans/embryology/*genetics/physiology ; *Caenorhabditis elegans Proteins ; *DNA-Binding Proteins ; Disorders of Sex Development ; *Dosage Compensation, Genetic ; Female ; Gene Expression Regulation, Developmental ; Genes, Helminth ; Helminth Proteins/genetics/*physiology ; Male ; Molecular Sequence Data ; Mutation ; Promoter Regions, Genetic ; Repressor Proteins/genetics/*physiology ; *Sex Determination Processes ; Transgenes ; X Chromosome/genetics/*metabolism
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  • 75
    Publication Date: 1999-04-09
    Description: Mature Arabidopsis seeds are enriched in storage proteins and lipids, but lack starch. In the shrunken seed 1 (sse1) mutant, however, starch is favored over proteins and lipids as the major storage compound. SSE1 has 26 percent identity with Pex16p in Yarrowia lipolytica and complements pex16 mutants defective in the formation of peroxisomes and the transportation of plasma membrane- and cell wall-associated proteins. In Arabidopsis maturing seeds, SSE1 is required for protein and oil body biogenesis, both of which are endoplasmic reticulum-dependent. Starch accumulation in sse1 suggests that starch formation is a default storage deposition pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lin, Y -- Sun, L -- Nguyen, L V -- Rachubinski, R A -- Goodman, H M -- New York, N.Y. -- Science. 1999 Apr 9;284(5412):328-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10195899" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arabidopsis/genetics/*metabolism/ultrastructure ; *Arabidopsis Proteins ; *Fungal Proteins ; Gene Expression ; Genetic Complementation Test ; Membrane Proteins/chemistry/genetics ; Microbodies/metabolism/ultrastructure ; Microscopy, Electron ; Molecular Sequence Data ; Mutation ; Organelles/*metabolism/ultrastructure ; Phenotype ; Plant Oils/metabolism ; Plant Proteins/chemistry/genetics/metabolism/*physiology ; Reverse Transcriptase Polymerase Chain Reaction ; Saccharomycetales/chemistry/genetics/metabolism ; Seeds/*metabolism/ultrastructure ; Starch/metabolism
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  • 76
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-02-12
    Description: The classical phylogeny of living reptiles pairs crocodilians with birds, tuataras with squamates, and places turtles at the base of the tree. New evidence from two nuclear genes, and analyses of mitochondrial DNA and 22 additional nuclear genes, join crocodilians with turtles and place squamates at the base of the tree. Morphological and paleontological evidence for this molecular phylogeny is unclear. Molecular time estimates support a Triassic origin for the major groups of living reptiles.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hedges, S B -- Poling, L L -- New York, N.Y. -- Science. 1999 Feb 12;283(5404):998-1001.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Institute of Molecular Evolutionary Genetics, and Astrobiology Research Center, 208 Mueller Laboratory, Pennsylvania State University, University Park, PA 16802, USA. sbh1@psu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9974396" target="_blank"〉PubMed〈/a〉
    Keywords: Alligators and Crocodiles/anatomy & histology/classification/genetics ; Animals ; Birds/anatomy & histology/classification/genetics ; Genes, rRNA ; Lizards/anatomy & histology/classification/genetics ; Molecular Sequence Data ; *Phylogeny ; RNA, Ribosomal, 18S/genetics ; Reptiles/anatomy & histology/*classification/*genetics ; Snakes/anatomy & histology/classification/genetics ; Turtles/anatomy & histology/classification/genetics
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  • 77
    Publication Date: 1999-01-05
    Description: CmPP16 from Cucurbita maxima was cloned and the protein was shown to possess properties similar to those of viral movement proteins. CmPP16 messenger RNA (mRNA) is present in phloem tissue, whereas protein appears confined to sieve elements (SE). Microinjection and grafting studies revealed that CmPP16 moves from cell to cell, mediates the transport of sense and antisense RNA, and moves together with its mRNA into the SE of scion tissue. CmPP16 possesses the characteristics that are likely required to mediate RNA delivery into the long-distance translocation stream. Thus, RNA may move within the phloem as a component of a plant information superhighway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xoconostle-Cazares, B -- Xiang, Y -- Ruiz-Medrano, R -- Wang, H L -- Monzer, J -- Yoo, B C -- McFarland, K C -- Franceschi, V R -- Lucas, W J -- New York, N.Y. -- Science. 1999 Jan 1;283(5398):94-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Plant Biology, Division of Biological Sciences, University of California, Davis, CA 95616, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9872750" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Biological Transport ; Cloning, Molecular ; Cucumis sativus ; Cucurbitaceae/genetics/*metabolism ; Microinjections ; Molecular Sequence Data ; Plant Leaves/metabolism ; Plant Proteins/chemistry/genetics/*metabolism ; Plant Roots/metabolism ; Plant Stems/metabolism ; Plant Viral Movement Proteins ; RNA, Antisense/metabolism ; RNA, Messenger/*metabolism ; RNA, Plant/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; Viral Proteins/chemistry/metabolism
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  • 78
    Publication Date: 1999-07-03
    Description: Epithelia permit selective and regulated flux from apical to basolateral surfaces by transcellular passage through cells or paracellular flux between cells. Tight junctions constitute the barrier to paracellular conductance; however, little is known about the specific molecules that mediate paracellular permeabilities. Renal magnesium ion (Mg2+) resorption occurs predominantly through a paracellular conductance in the thick ascending limb of Henle (TAL). Here, positional cloning has identified a human gene, paracellin-1 (PCLN-1), mutations in which cause renal Mg2+ wasting. PCLN-1 is located in tight junctions of the TAL and is related to the claudin family of tight junction proteins. These findings provide insight into Mg2+ homeostasis, demonstrate the role of a tight junction protein in human disease, and identify an essential component of a selective paracellular conductance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Simon, D B -- Lu, Y -- Choate, K A -- Velazquez, H -- Al-Sabban, E -- Praga, M -- Casari, G -- Bettinelli, A -- Colussi, G -- Rodriguez-Soriano, J -- McCredie, D -- Milford, D -- Sanjad, S -- Lifton, R P -- F.1/Telethon/Italy -- R01DK51696/DK/NIDDK NIH HHS/ -- TGM06S01/Telethon/Italy -- New York, N.Y. -- Science. 1999 Jul 2;285(5424):103-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10390358" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Calcium/urine ; Chromosomes, Human, Pair 3/genetics ; Claudins ; Cloning, Molecular ; Female ; Genes, Recessive ; Homeostasis ; Humans ; Kidney Diseases/*genetics/metabolism ; Kidney Tubules/chemistry ; Loop of Henle/chemistry/*metabolism ; Magnesium/blood/*metabolism ; Magnesium Deficiency/*genetics/metabolism ; Male ; Membrane Proteins/analysis/chemistry/genetics/*physiology ; Molecular Sequence Data ; Mutation ; Pedigree ; Physical Chromosome Mapping ; Tight Junctions/*metabolism
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  • 79
    Publication Date: 1999-10-16
    Description: Defensins contribute to host defense by disrupting the cytoplasmic membrane of microorganisms. This report shows that human beta-defensins are also chemotactic for immature dendritic cells and memory T cells. Human beta-defensin was selectively chemotactic for cells stably transfected to express human CCR6, a chemokine receptor preferentially expressed by immature dendritic cells and memory T cells. The beta-defensin-induced chemotaxis was sensitive to pertussis toxin and inhibited by antibodies to CCR6. The binding of iodinated LARC, the chemokine ligand for CCR6, to CCR6-transfected cells was competitively displaced by beta-defensin. Thus, beta-defensins may promote adaptive immune responses by recruiting dendritic and T cells to the site of microbial invasion through interaction with CCR6.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, D -- Chertov, O -- Bykovskaia, S N -- Chen, Q -- Buffo, M J -- Shogan, J -- Anderson, M -- Schroder, J M -- Wang, J M -- Howard, O M -- Oppenheim, J J -- N01-CO-56000/CO/NCI NIH HHS/ -- New York, N.Y. -- Science. 1999 Oct 15;286(5439):525-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Immunoregulation, Division of Basic Sciences, Intramural Research Support Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702-1201, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10521347" target="_blank"〉PubMed〈/a〉
    Keywords: Antibodies/immunology ; Binding, Competitive ; Cell Line ; Chemokine CCL20 ; Chemokines, CC/metabolism/pharmacology ; Chemotaxis ; Chemotaxis, Leukocyte ; Defensins ; Dendritic Cells/*immunology ; Humans ; *Immunity, Active ; *Immunity, Innate ; Immunologic Memory ; *Macrophage Inflammatory Proteins ; Pertussis Toxin ; Proteins/pharmacology/*physiology ; Receptors, CCR6 ; Receptors, Chemokine/genetics/*metabolism ; Recombinant Proteins/pharmacology ; T-Lymphocyte Subsets/*immunology ; Transfection ; Virulence Factors, Bordetella/pharmacology ; *beta-Defensins
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  • 80
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-04-24
    Description: Gene expression is modulated by regulatory elements that influence transcription elongation by RNA polymerase: terminators that disrupt the elongation complex and release RNA, and regulators that overcome termination signals. RNA release from Escherichia coli RNA polymerase can be induced by a complementary oligonucleotide that replaces the upstream half of the RNA hairpin stem of intrinsic terminator transcripts, implying that RNA hairpins act by extracting RNA from the transcription complex. A transcription antiterminator inhibits this activity of oligonucleotides and therefore protects the elongation complex from destabilizing attacks on the emerging transcript. These effects illuminate the structure of the complex and the mechanism of transcription termination.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yarnell, W S -- Roberts, J W -- GM 21941/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1999 Apr 23;284(5414):611-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Biochemistry, Molecular and Cell Biology, Biotechnology Building, Cornell University, Ithaca, NY 14853, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10213678" target="_blank"〉PubMed〈/a〉
    Keywords: Base Pairing ; Base Sequence ; DNA, Bacterial/chemistry/genetics/metabolism ; DNA-Directed RNA Polymerases/genetics/*metabolism ; Escherichia coli/*genetics/metabolism ; Models, Genetic ; Molecular Sequence Data ; Nucleic Acid Conformation ; Oligodeoxyribonucleotides/chemistry/metabolism ; RNA, Bacterial/chemistry/genetics/metabolism ; RNA, Messenger/chemistry/genetics/*metabolism ; Templates, Genetic ; *Terminator Regions, Genetic ; *Transcription, Genetic ; Viral Proteins/*metabolism
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  • 81
    Publication Date: 1999-04-09
    Description: IkappaB [inhibitor of nuclear factor kappaB (NF-kappaB)] kinase (IKK) phosphorylates IkappaB inhibitory proteins, causing their degradation and activation of transcription factor NF-kappaB, a master activator of inflammatory responses. IKK is composed of three subunits-IKKalpha and IKKbeta, which are highly similar protein kinases, and IKKgamma, a regulatory subunit. In mammalian cells, phosphorylation of two sites at the activation loop of IKKbeta was essential for activation of IKK by tumor necrosis factor and interleukin-1. Elimination of equivalent sites in IKKalpha, however, did not interfere with IKK activation. Thus, IKKbeta, not IKKalpha, is the target for proinflammatory stimuli. Once activated, IKKbeta autophosphorylated at a carboxyl-terminal serine cluster. Such phosphorylation decreased IKK activity and may prevent prolonged activation of the inflammatory response.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Delhase, M -- Hayakawa, M -- Chen, Y -- Karin, M -- R01 AI43477/AI/NIAID NIH HHS/ -- R37 ES04151/ES/NIEHS NIH HHS/ -- New York, N.Y. -- Science. 1999 Apr 9;284(5412):309-13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0636, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10195894" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Cell Line ; DNA-Binding Proteins/metabolism ; Enzyme Activation ; HeLa Cells ; Helix-Loop-Helix Motifs ; Humans ; I-kappa B Kinase ; I-kappa B Proteins ; Interleukin-1/pharmacology ; Leucine Zippers ; *MAP Kinase Kinase Kinase 1 ; Molecular Sequence Data ; Mutation ; Phosphorylation ; Phosphoserine/metabolism ; Protein-Serine-Threonine Kinases/chemistry/genetics/*metabolism ; Transfection ; Tumor Necrosis Factor-alpha/pharmacology
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  • 82
    Publication Date: 1999-04-16
    Description: Mutation of the VHL tumor suppressor is associated with the inherited von Hippel-Lindau (VHL) cancer syndrome and the majority of kidney cancers. VHL binds the ElonginC-ElonginB complex and regulates levels of hypoxia-inducible proteins. The structure of the ternary complex at 2.7 angstrom resolution shows two interfaces, one between VHL and ElonginC and another between ElonginC and ElonginB. Tumorigenic mutations frequently occur in a 35-residue domain of VHL responsible for ElonginC binding. A mutational patch on a separate domain of VHL indicates a second macromolecular binding site. The structure extends the similarities to the SCF (Skp1-Cul1-F-box protein) complex that targets proteins for degradation, supporting the hypothesis that VHL may function in an analogous pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stebbins, C E -- Kaelin, W G Jr -- Pavletich, N P -- New York, N.Y. -- Science. 1999 Apr 16;284(5413):455-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Structural Biology, Joan and Sanford I. Weill Graduate School of Medical Sciences, Cornell University, New York, NY 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10205047" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Cell Cycle Proteins/chemistry/metabolism ; Cloning, Molecular ; Crystallography, X-Ray ; *Genes, Tumor Suppressor ; Humans ; Hydrogen Bonding ; *Ligases ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Mutation, Missense ; Neoplasms/genetics ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Proteins/*chemistry/genetics/metabolism ; S-Phase Kinase-Associated Proteins ; Surface Properties ; Transcription Factors/*chemistry/metabolism ; *Tumor Suppressor Proteins ; *Ubiquitin-Protein Ligases ; Von Hippel-Lindau Tumor Suppressor Protein ; von Hippel-Lindau Disease/*genetics
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  • 83
    Publication Date: 1999-11-05
    Description: Focal adhesions (FAs) are clustered integrins and associated proteins that mediate cell adhesion and signaling. A green fluorescent protein-beta1 integrin chimera was used to label FAs in living cells. In stationary cells, FAs were highly motile, moving linearly for several plaque lengths toward the cell center. FA motility was independent of cell density and resulted from contraction of associated actin fibers. In migrating cells, FAs were stationary and only moved in the tail. FA motility in stationary cells suggests that cell movement may be regulated by a clutch-like mechanism by which the affinity of integrins to substrate may be altered in response to migratory cues.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smilenov, L B -- Mikhailov, A -- Pelham, R J -- Marcantonio, E E -- Gundersen, G G -- GM42026/GM/NIGMS NIH HHS/ -- GM44585/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1999 Nov 5;286(5442):1172-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Columbia University, New York, NY 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10550057" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Actins/physiology ; Animals ; Antigens, CD29/*metabolism ; *Cell Adhesion ; Cell Count ; Cell Line ; *Cell Movement ; Fibroblasts/*cytology/metabolism ; Fluorescence ; Green Fluorescent Proteins ; Luminescent Proteins ; Mice ; Microscopy, Interference ; Rats ; Recombinant Fusion Proteins/metabolism
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  • 84
    Publication Date: 1999-05-21
    Description: Bile acids regulate the transcription of genes that control cholesterol homeostasis through molecular mechanisms that are poorly understood. Physiological concentrations of free and conjugated chenodeoxycholic acid, lithocholic acid, and deoxycholic acid activated the farnesoid X receptor (FXR; NR1H4), an orphan nuclear receptor. As ligands, these bile acids and their conjugates modulated interaction of FXR with a peptide derived from steroid receptor coactivator 1. These results provide evidence for a nuclear bile acid signaling pathway that may regulate cholesterol homeostasis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Parks, D J -- Blanchard, S G -- Bledsoe, R K -- Chandra, G -- Consler, T G -- Kliewer, S A -- Stimmel, J B -- Willson, T M -- Zavacki, A M -- Moore, D D -- Lehmann, J M -- F32 DK09793/DK/NIDDK NIH HHS/ -- R01 DK53366/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1999 May 21;284(5418):1365-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biochemistry, Glaxo Wellcome Research and Development, Research Triangle Park NC, 27709, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10334993" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bile Acids and Salts/chemistry/*metabolism/pharmacology ; Carrier Proteins/metabolism ; Cell Line ; Chenodeoxycholic Acid/*metabolism/pharmacology ; Cholesterol/metabolism ; DNA-Binding Proteins/chemistry/genetics/*metabolism ; Deoxycholic Acid/metabolism/pharmacology ; Histone Acetyltransferases ; Homeostasis ; Humans ; Ligands ; Lithocholic Acid/metabolism/pharmacology ; Mice ; Nuclear Receptor Coactivator 1 ; *Organic Anion Transporters, Sodium-Dependent ; Protein Conformation ; Receptors, Cytoplasmic and Nuclear/chemistry/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; Structure-Activity Relationship ; *Symporters ; Transcription Factors/chemistry/genetics/*metabolism ; Transfection
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  • 85
    Publication Date: 1999-09-08
    Description: Photoperiodic responses in plants include flowering that is day-length-dependent. Mutations in the Arabidopsis thaliana GIGANTEA (GI) gene cause photoperiod-insensitive flowering and alteration of circadian rhythms. The GI gene encodes a protein containing six putative transmembrane domains. Circadian expression patterns of the GI gene and the clock-associated genes, LHY and CCA1, are altered in gi mutants, showing that GI is required for maintaining circadian amplitude and appropriate period length of these genes. The gi-1 mutation also affects light signaling to the clock, which suggests that GI participates in a feedback loop of the plant circadian system.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Park, D H -- Somers, D E -- Kim, Y S -- Choy, Y H -- Lim, H K -- Soh, M S -- Kim, H J -- Kay, S A -- Nam, H G -- GM56006/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1999 Sep 3;285(5433):1579-82.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Life Science, Pohang University of Science and Technology, Pohang, Kyungbuk, 790-784, Korea.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10477524" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/*genetics/*physiology ; *Arabidopsis Proteins ; *Circadian Rhythm ; Cloning, Molecular ; Crosses, Genetic ; DNA-Binding Proteins/genetics ; Darkness ; Feedback ; Gene Expression Regulation, Plant ; *Genes, Plant ; Light ; Molecular Sequence Data ; Mutation ; Photoperiod ; Plant Leaves/physiology ; Plant Proteins/chemistry/*genetics/physiology ; Plant Structures/physiology ; Sequence Deletion ; Transcription Factors/genetics
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  • 86
    Publication Date: 1999-10-26
    Description: T cell receptor (TCR)-induced apoptosis of thymocytes is mediated by calcium-dependent expression of the steroid receptors Nur77 and Nor1. Nur77 expression is controlled by the transcription factor myocyte enhancer factor 2 (MEF2), but how MEF2 is activated by calcium signaling is still obscure. Cabin1, a calcineurin inhibitor, was found to regulate MEF2. MEF2 was normally sequestered by Cabin1 in a transcriptionally inactive state. TCR engagement led to an increase in intracellular calcium concentration and the dissociation of MEF2 from Cabin1, as a result of competitive binding of activated calmodulin to Cabin1. The interplay between Cabin1, MEF2, and calmodulin defines a distinct signaling pathway from the TCR to the Nur77 promoter during T cell apoptosis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Youn, H D -- Sun, L -- Prywes, R -- Liu, J O -- GM55783/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1999 Oct 22;286(5440):790-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Cancer Research, Department of Biology, Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10531067" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing ; *Apoptosis ; Calcineurin/chemistry/genetics/metabolism/pharmacology ; Calcium/metabolism ; *Calcium Signaling ; Calmodulin/metabolism ; Cell Line ; DNA-Binding Proteins/chemistry/genetics/*metabolism ; Gene Expression ; Genes, Reporter ; Humans ; Jurkat Cells ; MEF2 Transcription Factors ; Myogenic Regulatory Factors ; Nuclear Receptor Subfamily 4, Group A, Member 1 ; Phosphoproteins/chemistry/genetics/metabolism/pharmacology ; Receptors, Antigen, T-Cell/metabolism ; Receptors, Cytoplasmic and Nuclear ; Receptors, Steroid ; T-Lymphocytes/*cytology/*metabolism ; Transcription Factors/chemistry/genetics/*metabolism ; Transcription, Genetic ; Two-Hybrid System Techniques
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  • 87
    Publication Date: 1999-05-29
    Description: Inositol 1,4,5-trisphosphate (IP3) is a second messenger that elicits complex spatiotemporal patterns of calcium ion (Ca2+) mobilization and has essential roles in the regulation of many cellular functions. In Madin-Darby canine kidney epithelial cells, green fluorescent protein-tagged pleckstrin homology domain translocated from the plasma membrane to the cytoplasm in response to increased concentration of IP3. The detection of translocation enabled monitoring of IP3 concentration changes within single cells and revealed spatiotemporal dynamics in the concentration of IP3 synchronous with Ca2+ oscillations and intracellular and intercellular IP3 waves that accompanied Ca2+ waves. Such changes in IP3 concentration may be fundamental to Ca2+ signaling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hirose, K -- Kadowaki, S -- Tanabe, M -- Takeshima, H -- Iino, M -- New York, N.Y. -- Science. 1999 May 28;284(5419):1527-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Faculty of Medicine, University of Tokyo and CREST, Japan Science and Technology Corporation, Tokyo 113-8654, Japan. hirose@calcium.cmp.m.u-tokyo.ac.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10348740" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/pharmacology ; Animals ; Calcium/*metabolism ; *Calcium Signaling ; Cell Line ; Cell Membrane/metabolism ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; Dogs ; Green Fluorescent Proteins ; Inositol 1,4,5-Trisphosphate/*metabolism ; Inositol Phosphates/metabolism ; Isoenzymes/chemistry/metabolism ; Ligands ; Luminescent Proteins ; Microscopy, Confocal ; Phosphatidylinositol 4,5-Diphosphate/metabolism ; Phospholipase C delta ; Recombinant Fusion Proteins/metabolism ; Time Factors ; Type C Phospholipases/chemistry/metabolism
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  • 88
    Publication Date: 1999-10-09
    Description: Norwalk virus, a noncultivatable human calicivirus, is the major cause of epidemic gastroenteritis in humans. The first x-ray structure of a calicivirus capsid, which consists of 180 copies of a single protein, has been determined by phase extension from a low-resolution electron microscopy structure. The capsid protein has a protruding (P) domain connected by a flexible hinge to a shell (S) domain that has a classical eight-stranded beta-sandwich motif. The structure of the P domain is unlike that of any other viral protein with a subdomain exhibiting a fold similar to that of the second domain in the eukaryotic translation elongation factor-Tu. This subdomain, located at the exterior of the capsid, has the largest sequence variation among Norwalk-like human caliciviruses and is likely to contain the determinants of strain specificity and cell binding.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Prasad, B V -- Hardy, M E -- Dokland, T -- Bella, J -- Rossmann, M G -- Estes, M K -- New York, N.Y. -- Science. 1999 Oct 8;286(5438):287-90.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Verna and Marrs Mclean Department of Biochemistry, Division of Molecular Virology, Baylor College of Medicine, Houston, TX 77030, USA. bprasad@bcm.tmc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10514371" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Capsid/*chemistry/metabolism ; *Capsid Proteins ; Cryoelectron Microscopy ; Crystallography, X-Ray ; Dimerization ; Genome, Viral ; Humans ; Hydrogen Bonding ; Image Processing, Computer-Assisted ; Models, Molecular ; Molecular Sequence Data ; Norwalk virus/*chemistry/genetics/physiology ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Recombinant Proteins/chemistry ; Virus Assembly
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  • 89
    Publication Date: 1999-07-31
    Description: Many psychotropic drugs interfere with the reuptake of dopamine, norepinephrine, and serotonin. Transport capacity is regulated by kinase-linked pathways, particularly those involving protein kinase C (PKC), resulting in transporter phosphorylation and sequestration. Phosphorylation and sequestration of the serotonin transporter (SERT) were substantially impacted by ligand occupancy. Ligands that can permeate the transporter, such as serotonin or the amphetamines, prevented PKC-dependent SERT phosphorylation. Nontransported SERT antagonists such as cocaine and antidepressants were permissive for SERT phosphorylation but blocked serotonin effects. PKC-dependent SERT sequestration was also blocked by serotonin. These findings reveal activity-dependent modulation of neurotransmitter reuptake and identify previously unknown consequences of amphetamine, cocaine, and antidepressant action.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ramamoorthy, S -- Blakely, R D -- DA07390/DA/NIDA NIH HHS/ -- New York, N.Y. -- Science. 1999 Jul 30;285(5428):763-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology and Center for Molecular Neuroscience, School of Medicine, Vanderbilt University, Nashville, TN 37232-6420, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10427004" target="_blank"〉PubMed〈/a〉
    Keywords: Antidepressive Agents/metabolism/pharmacology ; Biogenic Monoamines/metabolism/pharmacology ; Biotinylation ; Carrier Proteins/antagonists & inhibitors/*metabolism ; Cell Line ; Central Nervous System Agents/metabolism/*pharmacology ; Cocaine/metabolism/pharmacology ; Dextroamphetamine/metabolism/pharmacology ; Enzyme Activation ; Humans ; Ligands ; Membrane Glycoproteins/antagonists & inhibitors/*metabolism ; *Membrane Transport Proteins ; Models, Biological ; *Nerve Tissue Proteins ; Neurotransmitter Agents/metabolism/*pharmacology ; Phosphorylation ; Protein Kinase C/metabolism ; Protein Kinases/metabolism ; Serotonin/*metabolism/pharmacology ; Serotonin Antagonists/pharmacology ; Serotonin Plasma Membrane Transport Proteins ; Serotonin Uptake Inhibitors/metabolism/pharmacology ; Tetradecanoylphorbol Acetate/pharmacology
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  • 90
    Publication Date: 1999-10-09
    Description: Ubiquitination of receptor protein-tyrosine kinases (RPTKs) terminates signaling by marking active receptors for degradation. c-Cbl, an adapter protein for RPTKs, positively regulates RPTK ubiquitination in a manner dependent on its variant SRC homology 2 (SH2) and RING finger domains. Ubiquitin-protein ligases (or E3s) are the components of ubiquitination pathways that recognize target substrates and promote their ligation to ubiquitin. The c-Cbl protein acted as an E3 that can recognize tyrosine-phosphorylated substrates, such as the activated platelet-derived growth factor receptor, through its SH2 domain and that recruits and allosterically activates an E2 ubiquitin-conjugating enzyme through its RING domain. These results reveal an SH2-containing protein that functions as a ubiquitin-protein ligase and thus provide a distinct mechanism for substrate targeting in the ubiquitin system.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Joazeiro, C A -- Wing, S S -- Huang, H -- Leverson, J D -- Hunter, T -- Liu, Y C -- CA39780/CA/NCI NIH HHS/ -- R01 DK56558/DK/NIDDK NIH HHS/ -- T32CA09523/CA/NCI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1999 Oct 8;286(5438):309-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Salk Institute, Molecular Biology and Virology Laboratory, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10514377" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Cell Line ; Humans ; Ligases/chemistry/*metabolism ; Molecular Sequence Data ; Phosphotyrosine/metabolism ; Point Mutation ; Proto-Oncogene Proteins/chemistry/genetics/*metabolism ; Proto-Oncogene Proteins c-cbl ; Receptor Protein-Tyrosine Kinases/*metabolism ; Receptor, Platelet-Derived Growth Factor beta/metabolism ; Recombinant Fusion Proteins/metabolism ; Sequence Alignment ; Signal Transduction ; *Ubiquitin-Conjugating Enzymes ; Ubiquitin-Protein Ligases ; Ubiquitins/*metabolism ; src Homology Domains
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  • 91
    Publication Date: 1999-01-08
    Description: Cochlear frequency selectivity in lower vertebrates arises in part from electrical tuning intrinsic to the sensory hair cells. The resonant frequency is determined largely by the gating kinetics of calcium-activated potassium (BK) channels encoded by the slo gene. Alternative splicing of slo from chick cochlea generated kinetically distinct BK channels. Combination with accessory beta subunits slowed the gating kinetics of alpha splice variants but preserved relative differences between them. In situ hybridization showed that the beta subunit is preferentially expressed by low-frequency (apical) hair cells in the avian cochlea. Interaction of beta with alpha splice variants could provide the kinetic range needed for electrical tuning of cochlear hair cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ramanathan, K -- Michael, T H -- Jiang, G J -- Hiel, H -- Fuchs, P A -- DC00276/DC/NIDCD NIH HHS/ -- New York, N.Y. -- Science. 1999 Jan 8;283(5399):215-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Hearing Sciences, Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9880252" target="_blank"〉PubMed〈/a〉
    Keywords: Alternative Splicing ; Animals ; Calcium/metabolism ; Cell Line ; Electrophysiology ; Gene Expression ; Hair Cells, Auditory/*physiology ; Humans ; In Situ Hybridization ; *Ion Channel Gating ; Kinetics ; Large-Conductance Calcium-Activated Potassium Channel beta Subunits ; Large-Conductance Calcium-Activated Potassium Channels ; Membrane Potentials ; Patch-Clamp Techniques ; Potassium Channels/genetics/*physiology ; *Potassium Channels, Calcium-Activated ; Quail ; RNA, Messenger/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Transfection
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  • 92
    Publication Date: 1999-03-19
    Description: In higher plants, organogenesis occurs continuously from self-renewing apical meristems. Arabidopsis thaliana plants with loss-of-function mutations in the CLAVATA (CLV1, 2, and 3) genes have enlarged meristems and generate extra floral organs. Genetic analysis indicates that CLV1, which encodes a receptor kinase, acts with CLV3 to control the balance between meristem cell proliferation and differentiation. CLV3 encodes a small, predicted extracellular protein. CLV3 acts nonautonomously in meristems and is expressed at the meristem surface overlying the CLV1 domain. These proteins may act as a ligand-receptor pair in a signal transduction pathway, coordinating growth between adjacent meristematic regions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fletcher, J C -- Brand, U -- Running, M P -- Simon, R -- Meyerowitz, E M -- New York, N.Y. -- Science. 1999 Mar 19;283(5409):1911-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10082464" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arabidopsis/*cytology/genetics/growth & development/metabolism ; *Arabidopsis Proteins ; Cell Differentiation ; Cell Division ; Cloning, Molecular ; Gene Expression Regulation, Plant ; Genes, Plant ; In Situ Hybridization ; Ligands ; Meristem/*cytology/growth & development/metabolism ; Molecular Sequence Data ; Mutation ; Phenotype ; Plant Proteins/chemistry/genetics/*metabolism ; Plant Shoots/cytology ; RNA, Messenger/genetics/metabolism ; RNA, Plant/genetics/metabolism ; Receptor Protein-Tyrosine Kinases/genetics/metabolism ; Recombinant Fusion Proteins/metabolism ; *Signal Transduction
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  • 93
    Publication Date: 1999-07-10
    Description: Drug resistance of pathogens is an increasing problem whose underlying mechanisms are not fully understood. Cellular uptake of the major drugs against Trypanosoma brucei spp., the causative agents of sleeping sickness, is thought to occur through an unusual, so far unidentified adenosine transporter. Saccharomyces cerevisiae was used in a functional screen to clone a gene (TbAT1) from Trypanosoma brucei brucei that encodes a nucleoside transporter. When expressed in yeast, TbAT1 enabled adenosine uptake and conferred susceptibility to melaminophenyl arsenicals. Drug-resistant trypanosomes harbor a defective TbAT1 variant. The molecular identification of the entry route of trypanocides opens the way to approaches for diagnosis and treatment of drug-resistant sleeping sickness.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maser, P -- Sutterlin, C -- Kralli, A -- Kaminsky, R -- New York, N.Y. -- Science. 1999 Jul 9;285(5425):242-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Swiss Tropical Institute, CH-4002 Basel, Switzerland. Biozentrum, University of Basel, CH-4056 Basel, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10398598" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine/*metabolism ; Amino Acid Sequence ; Animals ; Arsenicals/metabolism/pharmacology ; Biological Transport ; Carrier Proteins/chemistry/genetics/*metabolism ; Cloning, Molecular ; Drug Resistance/genetics ; Genes, Protozoan ; Membrane Proteins/chemistry/genetics/*metabolism ; Molecular Sequence Data ; Mutation ; Nucleoside Transport Proteins ; Nucleosides/metabolism ; Purines/metabolism/pharmacology ; Saccharomyces cerevisiae/genetics ; Substrate Specificity ; Trypanocidal Agents/metabolism/*pharmacology ; Trypanosoma brucei brucei/*drug effects/genetics/*metabolism ; Trypanosomiasis, African/drug therapy/parasitology
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  • 94
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-04-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Solter, D -- Gearhart, J -- New York, N.Y. -- Science. 1999 Mar 5;283(5407):1468-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Developmental Biology, Max Planck Institute of Immunology, Freiburg, Germany. solter@immunbio.mpg.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10206877" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bioethics ; Blastocyst/*cytology ; *Cell Differentiation ; Cell Line ; Cells, Cultured ; Cloning, Organism ; Cytoplasm/physiology ; Embryo, Mammalian/cytology ; Humans ; Mice ; Nuclear Transfer Techniques ; Stem Cells/*cytology
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 95
    Publication Date: 1999-10-16
    Description: Analysis of rhesus macaque leukocytes disclosed the presence of an 18-residue macrocyclic, tridisulfide antibiotic peptide in granules of neutrophils and monocytes. The peptide, termed rhesus theta defensin-1 (RTD-1), is microbicidal for bacteria and fungi at low micromolar concentrations. Antibacterial activity of the cyclic peptide was threefold greater than that of an open-chain analog, and the cyclic conformation was required for antimicrobial activity in the presence of 150 millimolar sodium chloride. Biosynthesis of RTD-1 involves the head-to-tail ligation of two alpha-defensin-related nonapeptides, requiring the formation of two new peptide bonds. Thus, host defense cells possess mechanisms for synthesis and granular packaging of macrocyclic antibiotic peptides that are components of the phagocyte antimicrobial armamentarium.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tang, Y Q -- Yuan, J -- Osapay, G -- Osapay, K -- Tran, D -- Miller, C J -- Ouellette, A J -- Selsted, M E -- AI22931/AI/NIAID NIH HHS/ -- DK33506/DK/NIDDK NIH HHS/ -- DK44632/DK/NIDDK NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1999 Oct 15;286(5439):498-502.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, College of Medicine, University of California, Irvine, CA 92697, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10521339" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Anti-Bacterial Agents ; Anti-Infective Agents/chemistry/*metabolism/pharmacology ; Bacteria/drug effects ; Cloning, Molecular ; Defensins ; Disulfides/chemistry ; Fungi/drug effects ; Humans ; Leukopoiesis ; Macaca mulatta ; Molecular Sequence Data ; Monocytes/*metabolism ; Neutrophils/*metabolism ; Oligopeptides/chemistry/genetics/metabolism ; Osmolar Concentration ; Peptides, Cyclic/*biosynthesis/chemistry/genetics/pharmacology ; *Protein Biosynthesis ; Protein Conformation ; Protein Precursors/chemistry/genetics/metabolism ; Protein Processing, Post-Translational ; Proteins/chemistry/genetics/pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 96
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-07-15
    Description: Mutation at the mouse progressive ankylosis (ank) locus causes a generalized, progressive form of arthritis accompanied by mineral deposition, formation of bony outgrowths, and joint destruction. Here, we show that the ank locus encodes a multipass transmembrane protein (ANK) that is expressed in joints and other tissues and controls pyrophosphate levels in cultured cells. A highly conserved gene is present in humans and other vertebrates. These results identify ANK-mediated control of pyrophosphate levels as a possible mechanism regulating tissue calcification and susceptibility to arthritis in higher animals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ho, A M -- Johnson, M D -- Kingsley, D M -- 5T32GM07365/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 Jul 14;289(5477):265-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Developmental Biology and Howard Hughes Medical Institute, Beckman Center B300, Stanford University School of Medicine, Stanford, CA 94305-5327, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10894769" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arthritis/*genetics/metabolism/pathology ; Base Sequence ; Biological Transport ; COS Cells ; Calcinosis/*genetics ; Chromosome Mapping ; Cloning, Molecular ; Dna ; Diphosphates/*metabolism ; Durapatite/metabolism ; Gene Expression ; Genetic Complementation Test ; Humans ; Membrane Proteins/*genetics/metabolism/*physiology ; Mice ; Mice, Transgenic ; Molecular Sequence Data ; Mutation ; Phenotype ; Phosphate Transport Proteins ; Physical Chromosome Mapping ; Sequence Homology, Nucleic Acid ; Tissue Distribution
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 97
    Publication Date: 2000-09-01
    Description: Activation of the transcription factor nuclear factor (NF)-kappaB by proinflammatory stimuli leads to increased expression of genes involved in inflammation. Activation of NF-kappaB requires the activity of an inhibitor of kappaB (IkappaB)-kinase (IKK) complex containing two kinases (IKKalpha and IKKbeta) and the regulatory protein NEMO (NF-kappaB essential modifier). An amino-terminal alpha-helical region of NEMO associated with a carboxyl-terminal segment of IKKalpha and IKKbeta that we term the NEMO-binding domain (NBD). A cell-permeable NBD peptide blocked association of NEMO with the IKK complex and inhibited cytokine-induced NF-kappaB activation and NF-kappaB-dependent gene expression. The peptide also ameliorated inflammatory responses in two experimental mouse models of acute inflammation. The NBD provides a target for the development of drugs that would block proinflammatory activation of the IKK complex without inhibiting basal NF-kappaB activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉May, M J -- D'Acquisto, F -- Madge, L A -- Glockner, J -- Pober, J S -- Ghosh, S -- AI 33443/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2000 Sep 1;289(5484):1550-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10968790" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/chemistry/pharmacology ; COS Cells ; Cells, Cultured ; E-Selectin/biosynthesis/genetics ; Endothelium, Vascular/metabolism ; Gene Expression Regulation ; HeLa Cells ; Humans ; I-kappa B Kinase ; Inflammation/drug therapy ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Mutation ; NF-kappa B/*metabolism ; Peptides/chemistry/*pharmacology ; Point Mutation ; Protein Structure, Tertiary ; Protein-Serine-Threonine Kinases/chemistry/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 98
    Publication Date: 2000-03-04
    Description: The large chlorella virus PBCV-1, which contains double-stranded DNA (dsDNA), encodes a 94-codon open reading frame (ORF) that contains a motif resembling the signature sequence of the pore domain of potassium channel proteins. Phylogenetic analyses of the encoded protein, Kcv, indicate a previously unidentified type of potassium channel. The messenger RNA encoded by the ORF leads to functional expression of a potassium-selective conductance in Xenopus laevis oocytes. The channel blockers amantadine and barium, but not cesium, inhibit this conductance, in addition to virus plaque formation. Thus, PBCV-1 encodes the first known viral protein that functions as a potassium-selective channel and is essential in the virus life cycle.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Plugge, B -- Gazzarrini, S -- Nelson, M -- Cerana, R -- Van Etten, J L -- Derst, C -- DiFrancesco, D -- Moroni, A -- Thiel, G -- 971/Telethon/Italy -- GM32441/GM/NIGMS NIH HHS/ -- GM41333/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 Mar 3;287(5458):1641-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Albrecht-von-Haller-Institut fur Pflanzenwissenschaften, Universitat Gottingen, 37073 Gottingen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10698737" target="_blank"〉PubMed〈/a〉
    Keywords: Amantadine/pharmacology ; Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Barium/pharmacology ; Cesium/pharmacology ; Chlorella/virology ; Isoelectric Point ; Molecular Sequence Data ; Molecular Weight ; Oocytes ; Patch-Clamp Techniques ; Phycodnaviridae/chemistry/drug effects/*genetics/*physiology ; Potassium/metabolism ; Potassium Channels/*chemistry/genetics/*physiology ; RNA, Messenger/genetics/metabolism ; Recombinant Proteins/metabolism ; Sodium/metabolism ; Viral Plaque Assay ; *Viral Proteins ; Virus Replication/drug effects ; Xenopus laevis
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 99
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-07-06
    Description: In this month's essay, Anne McLaren traces the winding and pitted pathways that connect the early days of the cell theory of biology in the 1830s to the new and unfolding era of cloning science and technology that came to worldwide attention in 1997 with the announcement of the birth of Dolly, the Scottish cloned sheep. The possibilities, including the potential for new medical treatments and perhaps even human cloning, are fantastic ... and ethically charged.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McLaren, A -- New York, N.Y. -- Science. 2000 Jun 9;288(5472):1775-80.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome/CRC Institute, Cambridge, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10877698" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Domestic/embryology/genetics ; Bioethics ; Cell Differentiation ; Cell Line ; Cell Nucleus/physiology ; *Cloning, Organism/history/trends ; Cytoplasm/physiology ; Embryo, Mammalian/cytology ; Embryo, Nonmammalian/cytology ; History, 19th Century ; History, 20th Century ; Humans ; Nuclear Transfer Techniques ; Stem Cells/cytology/physiology ; Therapeutics
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 100
    Publication Date: 1999-12-30
    Description: The Smad proteins mediate transforming growth factor-beta (TGFbeta) signaling from the transmembrane serine-threonine receptor kinases to the nucleus. The Smad anchor for receptor activation (SARA) recruits Smad2 to the TGFbeta receptors for phosphorylation. The crystal structure of a Smad2 MH2 domain in complex with the Smad-binding domain (SBD) of SARA has been determined at 2.2 angstrom resolution. SARA SBD, in an extended conformation comprising a rigid coil, an alpha helix, and a beta strand, interacts with the beta sheet and the three-helix bundle of Smad2. Recognition between the SARA rigid coil and the Smad2 beta sheet is essential for specificity, whereas interactions between the SARA beta strand and the Smad2 three-helix bundle contribute significantly to binding affinity. Comparison of the structures between Smad2 and a comediator Smad suggests a model for how receptor-regulated Smads are recognized by the type I receptors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, G -- Chen, Y G -- Ozdamar, B -- Gyuricza, C A -- Chong, P A -- Wrana, J L -- Massague, J -- Shi, Y -- CA85171/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2000 Jan 7;287(5450):92-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Princeton, NJ 08544, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10615055" target="_blank"〉PubMed〈/a〉
    Keywords: *Activin Receptors, Type I ; Amino Acid Sequence ; Binding Sites ; Carrier Proteins/*chemistry/*metabolism ; Crystallography, X-Ray ; DNA-Binding Proteins/*chemistry/genetics/*metabolism ; Hydrogen Bonding ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Phosphorylation ; Point Mutation ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein-Serine-Threonine Kinases/chemistry/genetics/metabolism ; Receptors, Transforming Growth Factor beta/chemistry/genetics/metabolism ; Recombinant Fusion Proteins/chemistry/metabolism ; Signal Transduction ; Smad2 Protein ; Trans-Activators/*chemistry/genetics/*metabolism ; Zinc Fingers
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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