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  • Cell Line  (502)
  • Amino Acid Sequence  (481)
  • American Association for the Advancement of Science (AAAS)  (907)
  • Annual Reviews
  • Blackwell Publishing Ltd
  • Institute of Physics
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  • American Association for the Advancement of Science (AAAS)  (907)
  • Annual Reviews
  • Blackwell Publishing Ltd
  • Institute of Physics
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Year
  • 1
    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
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
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  • 2
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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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  • 3
    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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  • 4
    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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  • 5
    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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  • 6
    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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  • 7
    Publication Date: 2002-02-09
    Description: The protein-protein interaction between leukocyte functional antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) is critical to lymphocyte and immune system function. Here, we report on the transfer of the contiguous, nonlinear epitope of ICAM-1, responsible for its association with LFA-1, to a small-molecule framework. These LFA-1 antagonists bound LFA-1, blocked binding of ICAM-1, and inhibited a mixed lymphocyte reaction (MLR) with potency significantly greater than that of cyclosporine A. Furthermore, in comparison to an antibody to LFA-1, they exhibited significant anti-inflammatory effects in vivo. These results demonstrate the utility of small-molecule mimics of nonlinear protein epitopes and the protein epitopes themselves as leads in the identification of novel pharmaceutical agents.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gadek, T R -- Burdick, D J -- McDowell, R S -- Stanley, M S -- Marsters, J C Jr -- Paris, K J -- Oare, D A -- Reynolds, M E -- Ladner, C -- Zioncheck, K A -- Lee, W P -- Gribling, P -- Dennis, M S -- Skelton, N J -- Tumas, D B -- Clark, K R -- Keating, S M -- Beresini, M H -- Tilley, J W -- Presta, L G -- Bodary, S C -- New York, N.Y. -- Science. 2002 Feb 8;295(5557):1086-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioorganic Chemistry, Genentech, One DNA Way, South San Francisco, CA 94080, USA. trg@gene.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11834839" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/chemical ; synthesis/chemistry/metabolism/pharmacology ; Cyclosporine/pharmacology ; Dermatitis, Irritant/drug therapy ; Dinitrofluorobenzene ; Drug Design ; Enzyme-Linked Immunosorbent Assay ; Epitopes ; Female ; Humans ; Immunoglobulin Fab Fragments/immunology/pharmacology ; Immunosuppressive Agents/chemical synthesis/chemistry/metabolism/*pharmacology ; Intercellular Adhesion Molecule-1/chemistry/*immunology/*metabolism ; Lymphocyte Culture Test, Mixed ; Lymphocyte Function-Associated Antigen-1/immunology/*metabolism ; Mice ; Mice, Inbred BALB C ; Molecular Mimicry ; Mutagenesis ; Protein Structure, Secondary ; Structure-Activity Relationship ; Thiophenes/*chemical synthesis/chemistry/metabolism/*pharmacology ; beta-Alanine/analogs & derivatives/*chemical ; synthesis/chemistry/metabolism/*pharmacology
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  • 8
    Publication Date: 2002-02-09
    Description: Primary open-angle glaucoma (POAG) affects 33 million individuals worldwide and is a leading cause of blindness. In a study of 54 families with autosomal dominantly inherited adult-onset POAG, we identified the causative gene on chromosome 10p14 and designated it OPTN (for "optineurin"). Sequence alterations in OPTN were found in 16.7% of families with hereditary POAG, including individuals with normal intraocular pressure. The OPTN gene codes for a conserved 66-kilodalton protein of unknown function that has been implicated in the tumor necrosis factor-alpha signaling pathway and that interacts with diverse proteins including Huntingtin, Ras-associated protein RAB8, and transcription factor IIIA. Optineurin is expressed in trabecular meshwork, nonpigmented ciliary epithelium, retina, and brain, and we speculate that it plays a neuroprotective role.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rezaie, Tayebeh -- Child, Anne -- Hitchings, Roger -- Brice, Glen -- Miller, Lauri -- Coca-Prados, Miguel -- Heon, Elise -- Krupin, Theodore -- Ritch, Robert -- Kreutzer, Donald -- Crick, R Pitts -- Sarfarazi, Mansoor -- EY-09947/EY/NEI NIH HHS/ -- New York, N.Y. -- Science. 2002 Feb 8;295(5557):1077-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Ophthalmic Genetics Laboratory, Surgical Research Center, Department of Surgery, University of Connecticut Health Center, Farmington, CT 06030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11834836" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Alternative Splicing ; Amino Acid Sequence ; Brain/metabolism ; Chromosome Mapping ; Chromosomes, Human, Pair 10/genetics ; Ciliary Body/metabolism ; Exons ; Eye Proteins/analysis/chemistry/*genetics/physiology ; Female ; Glaucoma, Open-Angle/*genetics ; Golgi Apparatus/chemistry ; Heterozygote ; Humans ; Intraocular Pressure ; Male ; Middle Aged ; *Mutation ; *Mutation, Missense ; Nerve Tissue Proteins/analysis/chemistry/*genetics/physiology ; Ocular Hypertension/genetics ; Pedigree ; Polymorphism, Single-Stranded Conformational ; Retina/metabolism ; Trabecular Meshwork/metabolism ; *Transcription Factor TFIIIA ; Zinc Fingers
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  • 9
    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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  • 10
    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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  • 11
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    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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  • 12
    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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  • 13
    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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  • 14
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-02-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Calladine, C R -- Pratap, V -- Chandran, V -- Mizuguchi, K -- Luisi, B F -- New York, N.Y. -- Science. 2003 Jan 31;299(5607):661-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12561825" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Crystallography, X-Ray ; Escherichia coli Proteins/*chemistry ; Glycine/chemistry ; Ion Channels/*chemistry ; *Models, Molecular ; Protein Conformation ; Protein Structure, Secondary
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  • 15
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    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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  • 16
    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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  • 17
    Publication Date: 2003-06-14
    Description: In eukaryotes, the combinatorial association of sequence-specific DNA binding proteins is essential for transcription. We have used protein arrays to test 492 pairings of a nearly complete set of coiled-coil strands from human basic-region leucine zipper (bZIP) transcription factors. We find considerable partnering selectivity despite the bZIPs' homologous sequences. The interaction data are of high quality, as assessed by their reproducibility, reciprocity, and agreement with previous observations. Biophysical studies in solution support the relative binding strengths observed with the arrays. New associations provide insights into the circadian clock and the unfolded protein response.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Newman, John R S -- Keating, Amy E -- New York, N.Y. -- Science. 2003 Jun 27;300(5628):2097-101. Epub 2003 Jun 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12805554" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Basic-Leucine Zipper Transcription Factors ; Chromatography, High Pressure Liquid ; Circadian Rhythm ; Circular Dichroism ; Cyclic AMP Response Element-Binding Protein/chemistry/metabolism ; DNA-Binding Proteins/chemistry/isolation & purification/*metabolism ; Dimerization ; G-Box Binding Factors ; Humans ; *Leucine Zippers ; Peptides/chemistry/isolation & purification/metabolism ; *Protein Array Analysis ; Protein Binding ; Protein Folding ; Protein Structure, Tertiary ; Signal Transduction ; Temperature ; Thermodynamics ; Transcription Factors/*chemistry/isolation & purification/*metabolism
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  • 18
    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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  • 19
    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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  • 20
    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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  • 21
    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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  • 22
    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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  • 23
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    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
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  • 24
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Milligan, G -- New York, N.Y. -- Science. 2000 Apr 7;288(5463):65-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Scotland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10766637" target="_blank"〉PubMed〈/a〉
    Keywords: Adenylyl Cyclase Inhibitors ; Adenylyl Cyclases/metabolism ; Animals ; Cell Line ; Cerebral Cortex/metabolism ; Corpus Striatum/metabolism ; Dimerization ; Energy Transfer ; Fluorescence ; GTP-Binding Proteins/*metabolism ; Ligands ; Rats ; Receptor Cross-Talk ; Receptors, Dopamine D1/metabolism ; Receptors, Dopamine D2/agonists/*metabolism ; Receptors, Dopamine D5 ; Receptors, GABA-A/metabolism ; Receptors, Somatostatin/agonists/*metabolism ; Signal Transduction ; Somatostatin/metabolism
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  • 25
    Publication Date: 2000-10-20
    Description: Ectodysplasin, a member of the tumor necrosis factor family, is encoded by the anhidrotic ectodermal dysplasia (EDA) gene. Mutations in EDA give rise to a clinical syndrome characterized by loss of hair, sweat glands, and teeth. EDA-A1 and EDA-A2 are two isoforms of ectodysplasin that differ only by an insertion of two amino acids. This insertion functions to determine receptor binding specificity, such that EDA-A1 binds only the receptor EDAR, whereas EDA-A2 binds only the related, but distinct, X-linked ectodysplasin-A2 receptor (XEDAR). In situ binding and organ culture studies indicate that EDA-A1 and EDA-A2 are differentially expressed and play a role in epidermal morphogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yan, M -- Wang, L C -- Hymowitz, S G -- Schilbach, S -- Lee, J -- Goddard, A -- de Vos, A M -- Gao, W Q -- Dixit, V M -- New York, N.Y. -- Science. 2000 Oct 20;290(5491):523-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Oncology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11039935" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Binding Sites ; Cell Line ; DNA-Binding Proteins/metabolism ; Ectodermal Dysplasia/genetics ; Ectodysplasins ; Epidermis/embryology/*metabolism ; Humans ; *I-kappa B Proteins ; In Situ Hybridization ; Ligands ; Membrane Proteins/*chemistry/*metabolism ; Mice ; Models, Molecular ; Molecular Sequence Data ; Morphogenesis ; NF-kappa B/metabolism ; Phosphorylation ; Point Mutation ; Protein Conformation ; Proteins/metabolism ; Receptors, Cell Surface/chemistry/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; TNF Receptor-Associated Factor 6 ; Transfection
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  • 26
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-02-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aridor, M -- Balch, W E -- New York, N.Y. -- Science. 2000 Feb 4;287(5454):816-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Biology, Scripps Research Institute, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10691557" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Transport ; Cell Line ; Drug Delivery Systems ; Endoplasmic Reticulum/*metabolism/secretion ; Golgi Apparatus/metabolism ; Growth Hormone/chemistry/metabolism/secretion ; Immunophilins/chemistry/metabolism ; Insulin/chemistry/metabolism/secretion ; Ligands ; Mice ; Models, Biological ; Protein Conformation ; Protein Engineering ; Protein Folding ; Recombinant Fusion Proteins/*chemistry/*metabolism/secretion ; Tacrolimus Binding Proteins
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  • 27
    Publication Date: 2000-11-25
    Description: We generated a mutant of the red fluorescent protein drFP583. The mutant (E5) changes its fluorescence from green to red over time. The rate of color conversion is independent of protein concentration and therefore can be used to trace time-dependent expression. We used in vivo labeling with E5 to measure expression from the heat shock-dependent promoter in Caenorhabditis elegans and from the Otx-2 promoter in developing Xenopus embryos. Thus, E5 is a "fluorescent timer" that can be used to monitor both activation and down-regulation of target promoters on the whole-organism scale.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Terskikh, A -- Fradkov, A -- Ermakova, G -- Zaraisky, A -- Tan, P -- Kajava, A V -- Zhao, X -- Lukyanov, S -- Matz, M -- Kim, S -- Weissman, I -- Siebert, P -- 1 RO3 TW01362-01/TW/FIC NIH HHS/ -- New York, N.Y. -- Science. 2000 Nov 24;290(5496):1585-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Medicine, Stanford University, Stanford, CA 94305, USA. Alexey.Terskikh@Stanford.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11090358" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/embryology/metabolism ; Caenorhabditis elegans/embryology/genetics ; Cell Line ; Color ; Fluorescence ; Gene Expression Profiling/*methods ; *Gene Expression Regulation ; Gene Expression Regulation, Developmental ; Heat-Shock Proteins/genetics ; *Homeodomain Proteins ; Humans ; Luminescent Proteins/*chemistry/*genetics/metabolism ; Mutation ; Nerve Tissue Proteins/genetics ; Otx Transcription Factors ; *Promoter Regions, Genetic ; Temperature ; Time Factors ; Trans-Activators/genetics ; Xenopus laevis/embryology
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  • 28
    Publication Date: 2000-03-04
    Description: The coupling mechanism between endoplasmic reticulum (ER) calcium ion (Ca2+) stores and plasma membrane (PM) store-operated channels (SOCs) is crucial to Ca2+ signaling but has eluded detection. SOCs may be functionally related to the TRP family of receptor-operated channels. Direct comparison of endogenous SOCs with stably expressed TRP3 channels in human embryonic kidney (HEK293) cells revealed that TRP3 channels differ in being store independent. However, condensed cortical F-actin prevented activation of both SOC and TRP3 channels, which suggests that ER-PM interactions underlie coupling of both channels. A cell-permeant inhibitor of inositol trisphosphate receptor (InsP3R) function, 2-aminoethoxydiphenyl borate, prevented both receptor-induced TRP3 activation and store-induced SOC activation. It is concluded that InsP3Rs mediate both SOC and TRP channel opening and that the InsP3R is essential for maintaining coupling between store emptying and physiological activation of SOCs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ma, H T -- Patterson, R L -- van Rossum, D B -- Birnbaumer, L -- Mikoshiba, K -- Gill, D L -- AR07592/AR/NIAMS NIH HHS/ -- HL55426/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2000 Mar 3;287(5458):1647-51.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, University of Maryland, School of Medicine, Baltimore, MD 21201, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10698739" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/metabolism ; Boron Compounds/pharmacology ; Calcium/*metabolism ; Calcium Channels/chemistry/*metabolism ; *Calcium Signaling ; Carbachol/pharmacology ; Cell Line ; Cell Membrane/metabolism ; Diglycerides/metabolism/pharmacology ; Endoplasmic Reticulum/*metabolism ; Enzyme Inhibitors/pharmacology ; Humans ; Inositol 1,4,5-Trisphosphate Receptors ; Ionomycin/pharmacology ; Macrocyclic Compounds ; Oxazoles/pharmacology ; Phosphoprotein Phosphatases/antagonists & inhibitors ; Receptors, Cytoplasmic and Nuclear/chemistry/*metabolism ; Strontium/metabolism ; TRPC Cation Channels ; Thapsigargin/pharmacology ; Transfection ; Type C Phospholipases/metabolism
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  • 29
    Publication Date: 2000-10-20
    Description: Pseudomonas aeruginosa causes severe infections, particularly of the lung, that are life threatening. Here, we show that P. aeruginosa infection induces apoptosis of lung epithelial cells by activation of the endogenous CD95/CD95 ligand system. Deficiency of CD95 or CD95 ligand on epithelial cells prevented apoptosis of lung epithelial cells in vivo as well as in vitro. The importance of CD95/CD95 ligand-mediated lung epithelial cell apoptosis was demonstrated by the rapid development of sepsis in CD95- or CD95 ligand-deficient mice, but not in normal mice, after P. aeruginosa infection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grassme, H -- Kirschnek, S -- Riethmueller, J -- Riehle, A -- von Kurthy, G -- Lang, F -- Weller, M -- Gulbins, E -- New York, N.Y. -- Science. 2000 Oct 20;290(5491):527-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of Tuebingen, Gmelinstrasse 5, 72076 Tuebingen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11039936" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD95/genetics/*metabolism ; *Apoptosis ; Bone Marrow Transplantation ; Cell Line ; Epithelial Cells/*immunology/microbiology/pathology ; Fas Ligand Protein ; Humans ; In Situ Nick-End Labeling ; Lung/*immunology/microbiology/pathology ; Lung Diseases/*immunology/microbiology/pathology ; Membrane Glycoproteins/genetics/*metabolism ; Mice ; Mice, Inbred C3H ; Pseudomonas Infections/*immunology/microbiology/pathology ; Pseudomonas aeruginosa/immunology/*pathogenicity ; Sepsis/microbiology ; Spleen/microbiology
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  • 30
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-03-10
    Description: A Drosophila model for Huntington's and other polyglutamine diseases was used to screen for genetic factors modifying the degeneration caused by expression of polyglutamine in the eye. Among 7000 P-element insertions, several suppressor strains were isolated, two of which led to the discovery of the suppressor genes described here. The predicted product of one, dHDJ1, is homologous to human heat shock protein 40/HDJ1. That of the second, dTPR2, is homologous to the human tetratricopeptide repeat protein 2. Each of these molecules contains a chaperone-related J domain. Their suppression of polyglutamine toxicity was verified in transgenic flies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kazemi-Esfarjani, P -- Benzer, S -- New York, N.Y. -- Science. 2000 Mar 10;287(5459):1837-40.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA. parsa@its.caltech.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10710314" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Animals, Genetically Modified ; Cloning, Molecular ; Crosses, Genetic ; DNA Transposable Elements ; Disease Models, Animal ; *Drosophila Proteins ; Drosophila melanogaster/anatomy & histology/embryology/*genetics/metabolism ; Expressed Sequence Tags ; Eye/metabolism ; Eye Abnormalities ; Female ; Genes, Insect ; *Genes, Suppressor ; HSP40 Heat-Shock Proteins ; Heat-Shock Proteins/chemistry/*genetics/physiology ; Male ; Molecular Sequence Data ; *Nerve Degeneration ; Neurodegenerative Diseases ; Peptides/genetics/*metabolism ; Phenotype ; Proteins/chemistry ; Repetitive Sequences, Nucleic Acid ; Retina/metabolism ; Suppression, Genetic
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  • 31
    Publication Date: 2000-02-11
    Description: The nonclassical major histocompatibility complex (MHC) class I molecule HLA-E inhibits natural killer (NK) cell-mediated lysis by interacting with CD94/NKG2A receptors. Surface expression of HLA-E depends on binding of conserved peptides derived from MHC class I molecules. The same peptide is present in the leader sequence of the human cytomegalovirus (HCMV) glycoprotein UL40 (gpUL40). It is shown that, independently of the transporter associated with antigen processing, gpUL40 can up-regulate expression of HLA-E, which protects targets from NK cell lysis. While classical MHC class I molecules are down-regulated, HLA-E is up-regulated by HCMV. Induction of HLA-E surface expression by gpUL40 may represent an escape route for HCMV.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tomasec, P -- Braud, V M -- Rickards, C -- Powell, M B -- McSharry, B P -- Gadola, S -- Cerundolo, V -- Borysiewicz, L K -- McMichael, A J -- Wilkinson, G W -- New York, N.Y. -- Science. 2000 Feb 11;287(5455):1031.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, University of Wales College of Medicine, Cardiff CF14 4XN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10669413" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; *Antigens, CD ; Cell Line ; Cell Membrane/immunology ; Cells, Cultured ; Conserved Sequence ; Cytomegalovirus/genetics/immunology/*metabolism ; Cytotoxicity, Immunologic ; Down-Regulation ; HLA Antigens/immunology/*metabolism ; Histocompatibility Antigens Class I/immunology/*metabolism ; Humans ; Killer Cells, Natural/*immunology ; Molecular Sequence Data ; Open Reading Frames ; Protein Sorting Signals/chemistry/*metabolism ; Receptors, Immunologic/metabolism ; Recombinant Fusion Proteins/chemistry/metabolism ; Transfection ; Up-Regulation ; Viral Proteins/chemistry/genetics/*metabolism
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  • 32
    Publication Date: 2000-04-25
    Description: Susceptibility to murine and human insulin-dependent diabetes mellitus correlates strongly with major histocompatibility complex (MHC) class II I-A or HLA-DQ alleles that lack an aspartic acid at position beta57. I-Ag7 lacks this aspartate and is the only class II allele expressed by the nonobese diabetic mouse. The crystal structure of I-Ag7 was determined at 2.6 angstrom resolution as a complex with a high-affinity peptide from the autoantigen glutamic acid decarboxylase (GAD) 65. I-Ag7 has a substantially wider peptide-binding groove around beta57, which accounts for distinct peptide preferences compared with other MHC class II alleles. Loss of Asp(beta57) leads to an oxyanion hole in I-Ag7 that can be filled by peptide carboxyl residues or, perhaps, through interaction with the T cell receptor.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Corper, A L -- Stratmann, T -- Apostolopoulos, V -- Scott, C A -- Garcia, K C -- Kang, A S -- Wilson, I A -- Teyton, L -- CA58896/CA/NCI NIH HHS/ -- DK55037/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2000 Apr 21;288(5465):505-11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and Skaggs Institute for Chemical Biology, 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/10775108" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Aspartic Acid/chemistry ; Crystallography, X-Ray ; Diabetes Mellitus, Type 1/*immunology ; Drosophila melanogaster ; *Genes, MHC Class II ; Glutamate Decarboxylase/metabolism ; Histocompatibility Antigens Class II/*chemistry/genetics/metabolism ; Humans ; Hydrogen Bonding ; Mice ; Mice, Inbred NOD ; Models, Molecular ; Molecular Sequence Data ; Peptide Library ; Protein Binding ; Protein Conformation ; Protein Structure, Secondary ; Receptors, Antigen, T-Cell/metabolism ; Recombinant Proteins/chemistry/metabolism
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  • 33
    Publication Date: 2000-05-29
    Description: To protect genome integrity and ensure survival, eukaryotic cells exposed to genotoxic stress cease proliferating to provide time for DNA repair. Human cells responded to ultraviolet light or ionizing radiation by rapid, ubiquitin- and proteasome-dependent protein degradation of Cdc25A, a phosphatase that is required for progression from G1 to S phase of the cell cycle. This response involved activated Chk1 protein kinase but not the p53 pathway, and the persisting inhibitory tyrosine phosphorylation of Cdk2 blocked entry into S phase and DNA replication. Overexpression of Cdc25A bypassed this mechanism, leading to enhanced DNA damage and decreased cell survival. These results identify specific degradation of Cdc25A as part of the DNA damage checkpoint mechanism and suggest how Cdc25A overexpression in human cancers might contribute to tumorigenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mailand, N -- Falck, J -- Lukas, C -- Syljuasen, R G -- Welcker, M -- Bartek, J -- Lukas, J -- New York, N.Y. -- Science. 2000 May 26;288(5470):1425-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10827953" target="_blank"〉PubMed〈/a〉
    Keywords: *CDC2-CDC28 Kinases ; Cell Line ; Cell Survival ; Cyclin E/metabolism ; Cyclin-Dependent Kinase 2 ; Cyclin-Dependent Kinases/antagonists & inhibitors/metabolism ; Cysteine Endopeptidases/metabolism ; *DNA Damage ; DNA Repair ; DNA Replication ; G1 Phase ; Humans ; Multienzyme Complexes/metabolism ; Phosphorylation ; Phosphotyrosine/metabolism ; Proteasome Endopeptidase Complex ; Protein Kinase Inhibitors ; Protein Kinases/metabolism ; Protein-Serine-Threonine Kinases/antagonists & inhibitors/metabolism ; Recombinant Fusion Proteins/metabolism ; S Phase ; Transfection ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53/metabolism ; Ultraviolet Rays ; cdc25 Phosphatases/genetics/*metabolism
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  • 34
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-03-31
    Description: All cellular organisms use specialized RNA polymerases called "primases" to synthesize RNA primers for the initiation of DNA replication. The high-resolution crystal structure of a primase, comprising the catalytic core of the Escherichia coli DnaG protein, was determined. The core structure contains an active-site architecture that is unrelated to other DNA or RNA polymerase palm folds, but is instead related to the "toprim" fold. On the basis of the structure, it is likely that DnaG binds nucleic acid in a groove clustered with invariant residues and that DnaG is positioned within the replisome to accept single-stranded DNA directly from the replicative helicase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Keck, J L -- Roche, D D -- Lynch, A S -- Berger, J M -- New York, N.Y. -- Science. 2000 Mar 31;287(5462):2482-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, University of California, Berkeley, 229 Stanley Hall, no. 3206, Berkeley, CA 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10741967" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Binding Sites ; Catalytic Domain ; Crystallography, X-Ray ; DNA Helicases/chemistry/metabolism ; DNA Primase/*chemistry/*metabolism ; DNA Replication ; DNA, Bacterial/metabolism ; DNA, Single-Stranded/*metabolism ; DNA-Directed RNA Polymerases/*chemistry/metabolism ; Escherichia coli/*enzymology/metabolism ; Metals/metabolism ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Hybridization ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; RNA/biosynthesis ; Recombinant Proteins/chemistry/metabolism ; Templates, Genetic
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  • 35
    Publication Date: 2000-08-05
    Description: The circadian oscillator of the cyanobacterium Synechococcus elongatus, like those in eukaryotes, is entrained by environmental cues. Inactivation of the gene cikA (circadian input kinase) shortens the circadian period of gene expression rhythms in S. elongatus by approximately 2 hours, changes the phasing of a subset of rhythms, and nearly abolishes resetting of phase by a pulse of darkness. The CikA protein sequence reveals that it is a divergent bacteriophytochrome with characteristic histidine protein kinase motifs and a cryptic response regulator motif. CikA is likely a key component of a pathway that provides environmental input to the circadian oscillator in S. elongatus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schmitz, O -- Katayama, M -- Williams, S B -- Kondo, T -- Golden, S S -- GM37040/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 Aug 4;289(5480):765-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Texas A&M University, College Station, TX 77843-3258, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10926536" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Motifs ; Amino Acid Sequence ; *Bacterial Proteins ; *Biological Clocks/genetics/physiology ; *Circadian Rhythm/genetics/physiology ; Cyanobacteria/genetics/*physiology ; Gene Expression Regulation, Bacterial ; Genes, Bacterial ; Genes, Reporter ; Luminescent Measurements ; Molecular Sequence Data ; Mutation ; Phenotype ; Protein Kinases/chemistry/*genetics/physiology ; Sequence Alignment
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  • 36
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-09-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kennedy, D -- New York, N.Y. -- Science. 2000 Sep 1;289(5484):1469.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10991729" target="_blank"〉PubMed〈/a〉
    Keywords: Bioethics ; Cell Line ; Embryo, Mammalian/*cytology ; *Guidelines as Topic ; Humans ; *National Institutes of Health (U.S.) ; Politics ; *Research/legislation & jurisprudence ; Research Support as Topic ; *Stem Cells ; United States
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  • 37
    Publication Date: 2000-09-29
    Description: MyoD regulates skeletal muscle differentiation (SMD) and is essential for repair of damaged tissue. The transcription factor nuclear factor kappa B (NF-kappaB) is activated by the cytokine tumor necrosis factor (TNF), a mediator of skeletal muscle wasting in cachexia. Here, the role of NF-kappaB in cytokine-induced muscle degeneration was explored. In differentiating C2C12 myocytes, TNF-induced activation of NF-kappaB inhibited SMD by suppressing MyoD mRNA at the posttranscriptional level. In contrast, in differentiated myotubes, TNF plus interferon-gamma (IFN-gamma) signaling was required for NF-kappaB-dependent down-regulation of MyoD and dysfunction of skeletal myofibers. MyoD mRNA was also down-regulated by TNF and IFN-gamma expression in mouse muscle in vivo. These data elucidate a possible mechanism that may underlie the skeletal muscle decay in cachexia.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guttridge, D C -- Mayo, M W -- Madrid, L V -- Wang, C Y -- Baldwin, A S Jr -- AI35098/AI/NIAID NIH HHS/ -- CA72771/CA/NCI NIH HHS/ -- K01 CA78595/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2000 Sep 29;289(5488):2363-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lineberger Comprehensive Cancer Center, Curriculum in Genetics and Molecular Biology, Department of Biology, University of North Carolina, Chapel Hill, Mason Farm Road, Campus Box 7295, Chapel Hill, NC, 27599-7295, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11009425" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CHO Cells ; Cachexia/*etiology/metabolism/pathology ; Cell Differentiation ; Cell Line ; Cricetinae ; DNA-Binding Proteins/genetics/metabolism ; Down-Regulation ; *I-kappa B Proteins ; Interferon-gamma/pharmacology ; Interleukins/pharmacology ; Mice ; Mice, Inbred Strains ; Mice, Nude ; Muscle, Skeletal/*cytology/*metabolism/pathology ; MyoD Protein/*genetics/metabolism ; NF-kappa B/genetics/*metabolism ; RNA, Messenger/genetics/metabolism ; Transcription Factor RelA ; Transcription, Genetic ; Transfection ; Tumor Necrosis Factor-alpha/*pharmacology
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  • 38
    Publication Date: 2000-11-10
    Description: Reciprocal gene activation and restriction during cell type differentiation from a common lineage is a hallmark of mammalian organogenesis. A key question, then, is whether a critical transcriptional activator of cell type-specific gene targets can also restrict expression of the same genes in other cell types. Here, we show that whereas the pituitary-specific POU domain factor Pit-1 activates growth hormone gene expression in one cell type, the somatotrope, it restricts its expression from a second cell type, the lactotrope. This distinction depends on a two-base pair spacing in accommodation of the bipartite POU domains on a conserved growth hormone promoter site. The allosteric effect on Pit-1, in combination with other DNA binding factors, results in the recruitment of a corepressor complex, including nuclear receptor corepressor N-CoR, which, unexpectedly, is required for active long-term repression of the growth hormone gene in lactotropes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scully, K M -- Jacobson, E M -- Jepsen, K -- Lunyak, V -- Viadiu, H -- Carriere, C -- Rose, D W -- Hooshmand, F -- Aggarwal, A K -- Rosenfeld, M G -- R01 DK18477/DK/NIDDK NIH HHS/ -- R01 DK54802/DK/NIDDK NIH HHS/ -- R01 GM49327/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 Nov 10;290(5494):1127-31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Endocrinology and Metabolism, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11073444" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Animals ; Base Sequence ; Binding Sites ; Cell Line ; Conserved Sequence ; Crystallization ; DNA/*metabolism ; DNA-Binding Proteins/chemistry/genetics/*metabolism ; Female ; *Gene Expression Regulation ; Genes, Reporter ; Growth Hormone/*genetics ; Male ; Mice ; Mice, Transgenic ; Models, Molecular ; Molecular Sequence Data ; Nuclear Proteins/genetics/metabolism ; Nuclear Receptor Co-Repressor 1 ; Pituitary Gland/cytology/*metabolism ; Prolactin/*genetics ; Promoter Regions, Genetic ; Protein Conformation ; Protein Structure, Tertiary ; Rats ; Repressor Proteins/chemistry/genetics/*metabolism ; Transcription Factor Pit-1 ; Transcription Factors/chemistry/genetics/*metabolism ; Transcriptional Activation
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  • 39
    Publication Date: 2001-02-07
    Description: Atomic force microscopy and single-molecule force spectroscopy were combined to image and manipulate purple membrane patches from Halobacterium salinarum. Individual bacteriorhodopsin molecules were first localized and then extracted from the membrane; the remaining vacancies were imaged again. Anchoring forces between 100 and 200 piconewtons for the different helices were found. Upon extraction, the helices were found to unfold. The force spectra revealed the individuality of the unfolding pathways. Helices G and F as well as helices E and D always unfolded pairwise, whereas helices B and C occasionally unfolded one after the other. Experiments with cleaved loops revealed the origin of the individuality: stabilization of helix B by neighboring helices.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Oesterhelt, F -- Oesterhelt, D -- Pfeiffer, M -- Engel, A -- Gaub, H E -- Muller, D J -- New York, N.Y. -- Science. 2000 Apr 7;288(5463):143-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CeNS and Lehrstuhl fur angewandte Physik, Ludwig Maximilians-Universitat Munchen, Amalienstrasse 54, 80799 Munchen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10753119" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacteriorhodopsins/*chemistry/genetics ; Cysteine/chemistry ; Halobacterium salinarum/*chemistry ; Membrane Proteins/*chemistry/genetics ; *Microscopy, Atomic Force ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Protein Conformation ; Protein Denaturation ; *Protein Folding ; Protein Structure, Secondary ; Purple Membrane/*chemistry ; Serine Endopeptidases/metabolism ; Spectrum Analysis
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  • 40
    Publication Date: 2000-02-26
    Description: The signal recognition particle (SRP), a protein-RNA complex conserved in all three kingdoms of life, recognizes and transports specific proteins to cellular membranes for insertion or secretion. We describe here the 1.8 angstrom crystal structure of the universal core of the SRP, revealing protein recognition of a distorted RNA minor groove. Nucleotide analog interference mapping demonstrates the biological importance of observed interactions, and genetic results show that this core is functional in vivo. The structure explains why the conserved residues in the protein and RNA are required for SRP assembly and defines a signal sequence recognition surface composed of both protein and RNA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Batey, R T -- Rambo, R P -- Lucast, L -- Rha, B -- Doudna, J A -- New York, N.Y. -- Science. 2000 Feb 18;287(5456):1232-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University, New Haven, CT 06511, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10678824" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacterial Proteins/*chemistry/metabolism ; Base Pairing ; Binding Sites ; Cell Membrane/metabolism ; Crystallography, X-Ray ; Escherichia coli/chemistry/genetics/metabolism ; *Escherichia coli Proteins ; Guanosine Triphosphate/metabolism ; Hydrogen Bonding ; Magnesium/metabolism ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; Potassium/metabolism ; Protein Binding ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; RNA, Bacterial/*chemistry/genetics/metabolism ; Signal Recognition Particle/*chemistry/metabolism ; Transformation, Bacterial ; Water/metabolism
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  • 41
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-01-29
    Description: Evidence of simian immunodeficiency virus (SIV) infection has been reported for 26 different species of African nonhuman primates. Two of these viruses, SIVcpz from chimpanzees and SIVsm from sooty mangabeys, are the cause of acquired immunodeficiency syndrome (AIDS) in humans. Together, they have been transmitted to humans on at least seven occasions. The implications of human infection by a diverse set of SIVs and of exposure to a plethora of additional human immunodeficiency virus-related viruses are discussed.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hahn, B H -- Shaw, G M -- De Cock, K M -- Sharp, P M -- N01 AI 35338/AI/NIAID NIH HHS/ -- R01 AI 40951/AI/NIAID NIH HHS/ -- R01 AI 44596/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2000 Jan 28;287(5453):607-14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Howard Hughes Medical Institute, University of Alabama at Birmingham, Birmingham, AL 35294, USA. bhahn@uab.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10649986" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/epidemiology/*transmission/virology ; Africa, Western/epidemiology ; Amino Acid Sequence ; Animals ; Disease Outbreaks ; Disease Reservoirs ; *HIV-1/genetics ; *HIV-2/genetics ; Haplorhini/*virology ; Humans ; Molecular Sequence Data ; Phylogeny ; Public Health ; Simian Acquired Immunodeficiency Syndrome/virology ; Simian Immunodeficiency Virus/classification/genetics/*physiology ; Species Specificity ; Zoonoses/*transmission
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  • 42
    Publication Date: 2000-09-16
    Description: Extremely halophilic archaea contain retinal-binding integral membrane proteins called bacteriorhodopsins that function as light-driven proton pumps. So far, bacteriorhodopsins capable of generating a chemiosmotic membrane potential in response to light have been demonstrated only in halophilic archaea. We describe here a type of rhodopsin derived from bacteria that was discovered through genomic analyses of naturally occuring marine bacterioplankton. The bacterial rhodopsin was encoded in the genome of an uncultivated gamma-proteobacterium and shared highest amino acid sequence similarity with archaeal rhodopsins. The protein was functionally expressed in Escherichia coli and bound retinal to form an active, light-driven proton pump. The new rhodopsin exhibited a photochemical reaction cycle with intermediates and kinetics characteristic of archaeal proton-pumping rhodopsins. Our results demonstrate that archaeal-like rhodopsins are broadly distributed among different taxa, including members of the domain Bacteria. Our data also indicate that a previously unsuspected mode of bacterially mediated light-driven energy generation may commonly occur in oceanic surface waters worldwide.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Beja, O -- Aravind, L -- Koonin, E V -- Suzuki, M T -- Hadd, A -- Nguyen, L P -- Jovanovich, S B -- Gates, C M -- Feldman, R A -- Spudich, J L -- Spudich, E N -- DeLong, E F -- HG01775-02S1/HG/NHGRI NIH HHS/ -- R01GM27750/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 Sep 15;289(5486):1902-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Monterey Bay Aquarium Research Institute, Moss Landing, CA 95039-0628, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10988064" target="_blank"〉PubMed〈/a〉
    Keywords: Aerobiosis ; Amino Acid Sequence ; Archaea/classification/physiology ; Bacteria/genetics ; *Bacterial Physiological Phenomena ; Cloning, Molecular ; Escherichia coli ; Gammaproteobacteria/classification/genetics/*physiology ; Molecular Sequence Data ; Oceans and Seas ; Photochemistry ; Photosynthesis ; Phylogeny ; Phytoplankton/genetics/physiology ; Protein Binding ; Proton Pumps/physiology ; Retinaldehyde/metabolism ; Rhodopsin/*physiology ; Rhodopsins, Microbial ; *Water Microbiology
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  • 43
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-02-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Service, R F -- New York, N.Y. -- Science. 2000 Mar 17;287(5460):1954-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10755949" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Biotechnology ; Computer Simulation ; Crystallography, X-Ray ; *Drug Design ; Humans ; Models, Molecular ; Private Sector ; *Protein Conformation ; Protein Folding ; Proteins/*chemistry/*genetics/physiology ; Proteome ; Public Sector ; Research Support as Topic
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  • 44
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-02-26
    Description: Spider flagelliform silk is one of the most elastic natural materials known. Extensive sequencing of spider silk genes has shown that the exons and introns of the flagelliform gene underwent intragenic concerted evolution. The intron sequences are more homogenized within a species than are the exons. This pattern can be explained by extreme mutation and recombination pressures on the internally repetitive exons. The iterated sequences within exons encode protein structures that are critical to the function of silks. Therefore, attributes that make silks exceptional biomaterials may also hinder the fixation of optimally adapted protein sequences.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hayashi, C Y -- Lewis, R V -- New York, N.Y. -- Science. 2000 Feb 25;287(5457):1477-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, University of Wyoming, Laramie, WY 82071-3944, USA. hayashi@uwyo.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10688794" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Base Sequence ; Crossing Over, Genetic ; DNA/genetics ; DNA Replication ; *Evolution, Molecular ; *Exons ; Gene Conversion ; *Genes ; *Introns ; Molecular Sequence Data ; Mutation ; Proteins/chemistry/*genetics ; Recombination, Genetic ; Repetitive Sequences, Nucleic Acid ; Selection, Genetic ; Species Specificity ; Spiders/*genetics
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  • 45
    Publication Date: 2001-10-06
    Description: The definition of centromeres of human chromosomes requires a complete genomic understanding of these regions. Toward this end, we report integration of physical mapping, genetic, and functional approaches, together with sequencing of selected regions, to define the centromere of the human X chromosome and to explore the evolution of sequences responsible for chromosome segregation. The transitional region between expressed sequences on the short arm of the X and the chromosome-specific alpha satellite array DXZ1 spans about 450 kilobases and is satellite-rich. At the junction between this satellite region and canonical DXZ1 repeats, diverged repeat units provide direct evidence of unequal crossover as the homogenizing force of these arrays. Results from deletion analysis of mitotically stable chromosome rearrangements and from a human artificial chromosome assay demonstrate that DXZ1 DNA is sufficient for centromere function. Evolutionary studies indicate that, while alpha satellite DNA present throughout the pericentromeric region of the X chromosome appears to be a descendant of an ancestral primate centromere, the current functional centromere based on DXZ1 sequences is the product of the much more recent concerted evolution of this satellite DNA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schueler, M G -- Higgins, A W -- Rudd, M K -- Gustashaw, K -- Willard, H F -- HD07518/HD/NICHD NIH HHS/ -- HD32111/HD/NICHD NIH HHS/ -- HG00107/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2001 Oct 5;294(5540):109-15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Case Western Reserve University School of Medicine and Center for Human Genetics, and, Research Institute, University Hospitals of Cleveland, Cleveland, OH 44106, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11588252" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cell Line ; Centromere/chemistry/genetics/*physiology ; Chromosome Segregation ; Chromosomes, Artificial, Bacterial ; Chromosomes, Artificial, Human ; Computer Simulation ; Contig Mapping ; Crossing Over, Genetic ; *DNA, Satellite/chemistry/genetics/physiology ; Evolution, Molecular ; Humans ; Interspersed Repetitive Sequences ; Models, Genetic ; Phylogeny ; Repetitive Sequences, Nucleic Acid ; Restriction Mapping ; Sequence Analysis, DNA ; Sequence Deletion ; Sequence Tagged Sites ; Transfection ; Turner Syndrome/genetics ; X Chromosome/genetics/*physiology/ultrastructure
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  • 46
    Publication Date: 2001-04-21
    Description: Structures of a 10-subunit yeast RNA polymerase II have been derived from two crystal forms at 2.8 and 3.1 angstrom resolution. Comparison of the structures reveals a division of the polymerase into four mobile modules, including a clamp, shown previously to swing over the active center. In the 2.8 angstrom structure, the clamp is in an open state, allowing entry of straight promoter DNA for the initiation of transcription. Three loops extending from the clamp may play roles in RNA unwinding and DNA rewinding during transcription. A 2.8 angstrom difference Fourier map reveals two metal ions at the active site, one persistently bound and the other possibly exchangeable during RNA synthesis. The results also provide evidence for RNA exit in the vicinity of the carboxyl-terminal repeat domain, coupling synthesis to RNA processing by enzymes bound to this domain.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cramer, P -- Bushnell, D A -- Kornberg, R D -- GM49985/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2001 Jun 8;292(5523):1863-76. Epub 2001 Apr 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305-5126, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11313498" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Conserved Sequence ; Crystallography, X-Ray ; DNA, Fungal/chemistry/metabolism ; Fourier Analysis ; Hydrogen Bonding ; Magnesium/metabolism ; Metals/metabolism ; Models, Molecular ; Molecular Sequence Data ; Promoter Regions, Genetic ; Protein Conformation ; Protein Structure, Quaternary ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein Subunits ; RNA Polymerase II/*chemistry/*metabolism ; RNA Processing, Post-Transcriptional ; RNA, Fungal/biosynthesis/chemistry/metabolism ; RNA, Messenger/biosynthesis/chemistry/metabolism ; Saccharomyces cerevisiae/*enzymology/genetics ; Transcription Factors/metabolism ; *Transcription, Genetic
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  • 47
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-08-11
    Description: Chromatin, the physiological template of all eukaryotic genetic information, is subject to a diverse array of posttranslational modifications that largely impinge on histone amino termini, thereby regulating access to the underlying DNA. Distinct histone amino-terminal modifications can generate synergistic or antagonistic interaction affinities for chromatin-associated proteins, which in turn dictate dynamic transitions between transcriptionally active or transcriptionally silent chromatin states. The combinatorial nature of histone amino-terminal modifications thus reveals a "histone code" that considerably extends the information potential of the genetic code. We propose that this epigenetic marking system represents a fundamental regulatory mechanism that has an impact on most, if not all, chromatin-templated processes, with far-reaching consequences for cell fate decisions and both normal and pathological development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jenuwein, T -- Allis, C D -- GM53512/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2001 Aug 10;293(5532):1074-80.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Research Institute of Molecular Pathology (IMP) at the Vienna Biocenter, Dr. Bohrgasse 7, A-1030 Vienna, Austria. jenuwein@nt.imp.univie.ac.at〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11498575" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Amino Acid Sequence ; Animals ; Chromatin/chemistry/metabolism/ultrastructure ; *Gene Expression Regulation ; *Gene Silencing ; Genomic Imprinting ; Histones/chemistry/genetics/*metabolism ; Methylation ; Molecular Sequence Data ; Phosphorylation ; Protein Structure, Tertiary ; Transcription, Genetic ; Transcriptional Activation
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  • 48
    Publication Date: 2001-11-10
    Description: We describe a molecular switch based on the controlled methylation of nucleosome and the transcriptional cofactors, the CREB-binding proteins (CBP)/p300. The CBP/p300 methylation site is localized to an arginine residue that is essential for stabilizing the structure of the KIX domain, which mediates CREB recruitment. Methylation of KIX by coactivator-associated arginine methyltransferase 1 (CARM1) blocks CREB activation by disabling the interaction between KIX and the kinase inducible domain (KID) of CREB. Thus, CARM1 functions as a corepressor in cyclic adenosine monophosphate signaling pathway via its methyltransferase activity while acting as a coactivator for nuclear hormones. These results provide strong in vivo and in vitro evidence that histone methylation plays a key role in hormone-induced gene activation and define cofactor methylation as a new regulatory mechanism in hormone signaling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xu, W -- Chen, H -- Du, K -- Asahara, H -- Tini, M -- Emerson, B M -- Montminy, M -- Evans, R M -- 9R01DK57978/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2001 Dec 21;294(5551):2507-11. Epub 2001 Nov 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gene Expression Laboratory, Department of Biological Chemistry, University of California Davis Cancer Center/Basic Science, Sacramento, CA 95817, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11701890" target="_blank"〉PubMed〈/a〉
    Keywords: Acetyltransferases/metabolism ; Amino Acid Sequence ; Animals ; Apoptosis ; Cell Line ; Cyclic AMP Response Element-Binding Protein/metabolism ; Dimerization ; E1A-Associated p300 Protein ; *Gene Expression Regulation ; Genes, Reporter ; Histone Acetyltransferases ; Histones/metabolism ; Methylation ; Molecular Sequence Data ; Nerve Growth Factor/pharmacology ; Nuclear Proteins/chemistry/*metabolism ; PC12 Cells ; Protein Structure, Tertiary ; Protein-Arginine N-Methyltransferases/*metabolism ; Rats ; Receptors, Retinoic Acid/*metabolism ; Recombinant Fusion Proteins/metabolism ; Retinoid X Receptors ; *Saccharomyces cerevisiae Proteins ; Signal Transduction ; Somatostatin/genetics ; Trans-Activators/chemistry/*metabolism ; Transcription Factors/metabolism ; *Transcription, Genetic ; Transcriptional Activation ; Transfection ; Tretinoin/metabolism/pharmacology
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  • 49
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-05-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lanza, R P -- Cibelli, J B -- West, M D -- Dorff, E -- Tauer, C -- Green, R M -- New York, N.Y. -- Science. 2001 May 18;292(5520):1299.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11360981" target="_blank"〉PubMed〈/a〉
    Keywords: *Bioethics ; Cell Differentiation ; Cell Line ; *Embryo Research ; Embryo, Mammalian/cytology ; Financing, Organized ; *Government Regulation ; Humans ; National Institutes of Health (U.S.) ; Regeneration ; Research/economics/*legislation & jurisprudence/standards ; *Stem Cells/cytology ; United States ; United States Dept. of Health and Human Services
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  • 50
    Publication Date: 2001-04-17
    Description: In mammals, the central circadian pacemaker resides in the hypothalamic suprachiasmatic nucleus (SCN), but circadian oscillators also exist in peripheral tissues. Here, using wild-type and cryptochrome (mCry)-deficient cell lines derived from mCry mutant mice, we show that the peripheral oscillator in cultured fibroblasts is identical to the oscillator in the SCN in (i) temporal expression profiles of all known clock genes, (ii) the phase of the various mRNA rhythms (i.e., antiphase oscillation of Bmal1 and mPer genes), (iii) the delay between maximum mRNA levels and appearance of nuclear mPER1 and mPER2 protein, (iv) the inability to produce oscillations in the absence of functional mCry genes, and (v) the control of period length by mCRY proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yagita, K -- Tamanini, F -- van Der Horst, G T -- Okamura, H -- New York, N.Y. -- Science. 2001 Apr 13;292(5515):278-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Molecular Brain Science, Department of Brain Sciences, Kobe University Graduate School of Medicine, Chuo-ku, Kobe 650-0017, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11303101" target="_blank"〉PubMed〈/a〉
    Keywords: ARNTL Transcription Factors ; Animals ; Basic Helix-Loop-Helix Transcription Factors ; Biological Clocks/*genetics ; CLOCK Proteins ; Cell Cycle Proteins ; Cell Line ; Cell Nucleus/metabolism ; Circadian Rhythm/*genetics ; Cryptochromes ; *DNA-Binding Proteins ; *Drosophila Proteins ; Endothelin-1/pharmacology ; *Eye Proteins ; Fibroblasts/*physiology ; Flavoproteins/genetics/metabolism ; Gene Expression Profiling ; *Gene Expression Regulation ; Nuclear Proteins/genetics/metabolism ; Period Circadian Proteins ; *Photoreceptor Cells, Invertebrate ; RNA, Messenger/genetics/metabolism ; Rats ; Receptors, G-Protein-Coupled ; Suprachiasmatic Nucleus/metabolism ; Time Factors ; Trans-Activators/genetics/metabolism ; Transcription Factors/genetics/metabolism
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  • 51
    Publication Date: 2001-05-12
    Description: Telomere proteins from ciliated protozoa bind to the single-stranded G-rich DNA extensions at the ends of macronuclear chromosomes. We have now identified homologous proteins in fission yeast and in humans. These Pot1 (protection of telomeres) proteins each bind the G-rich strand of their own telomeric repeat sequence, consistent with a direct role in protecting chromosome ends. Deletion of the fission yeast pot1+ gene has an immediate effect on chromosome stability, causing rapid loss of telomeric DNA and chromosome circularization. It now appears that the protein that caps the ends of chromosomes is widely dispersed throughout the eukaryotic kingdom.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baumann, P -- Cech, T R -- New York, N.Y. -- Science. 2001 May 11;292(5519):1171-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11349150" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Binding Sites ; Chromosome Segregation/genetics ; Chromosomes, Fungal/genetics/metabolism ; Cloning, Molecular ; DNA/genetics/metabolism ; DNA-Binding Proteins/chemistry/genetics/*metabolism ; Electrophoresis, Gel, Pulsed-Field ; Female ; Gene Deletion ; Gene Expression Profiling ; Heterozygote ; Humans ; Molecular Sequence Data ; Ovary/metabolism ; Phenotype ; RNA, Messenger/analysis/genetics ; Schizosaccharomyces/*genetics ; Schizosaccharomyces pombe Proteins ; Sequence Alignment ; Substrate Specificity ; Telomere/genetics/*metabolism ; *Telomere-Binding Proteins
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  • 52
    Publication Date: 2001-06-02
    Description: Transcription elongation by RNA polymerase II (RNAPII) is negatively regulated by the human factors DRB-sensitivity inducing factor (DSIF) and negative elongation factor (NELF). A 66-kilodalton subunit of NELF (NELF-A) shows limited sequence similarity to hepatitis delta antigen (HDAg), the viral protein required for replication of hepatitis delta virus (HDV). The host RNAPII has been implicated in HDV replication, but the detailed mechanism and the role of HDAg in this process are not understood. We show that HDAg binds RNAPII directly and stimulates transcription by displacing NELF and promoting RNAPII elongation. These results suggest that HDAg may regulate RNAPII elongation during both cellular messenger RNA synthesis and HDV RNA replication.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yamaguchi, Y -- Filipovska, J -- Yano, K -- Furuya, A -- Inukai, N -- Narita, T -- Wada, T -- Sugimoto, S -- Konarska, M M -- Handa, H -- New York, N.Y. -- Science. 2001 Jul 6;293(5527):124-7. Epub 2001 May 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Frontier Collaborative Research Center, Tokyo Institute of Technology, 4259 Nagatsuta, Yokohama 226-8503, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11387440" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Consensus Sequence/genetics ; Enzyme Activation ; HeLa Cells ; Hepatitis Antigens/chemistry/*metabolism ; *Hepatitis Delta Virus/chemistry/genetics/metabolism ; Hepatitis delta Antigens ; Humans ; Molecular Sequence Data ; Protein Binding ; Protein Subunits ; RNA Polymerase II/*metabolism ; RNA, Viral/biosynthesis/genetics ; Sequence Alignment ; Templates, Genetic ; Transcription Factors/antagonists & inhibitors/chemistry/metabolism ; *Transcription, Genetic ; Virus Replication
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  • 53
    Publication Date: 2001-06-26
    Description: Clinical studies with the Abl tyrosine kinase inhibitor STI-571 in chronic myeloid leukemia demonstrate that many patients with advanced stage disease respond initially but then relapse. Through biochemical and molecular analysis of clinical material, we find that drug resistance is associated with the reactivation of BCR-ABL signal transduction in all cases examined. In six of nine patients, resistance was associated with a single amino acid substitution in a threonine residue of the Abl kinase domain known to form a critical hydrogen bond with the drug. This substitution of threonine with isoleucine was sufficient to confer STI-571 resistance in a reconstitution experiment. In three patients, resistance was associated with progressive BCR-ABL gene amplification. These studies provide evidence that genetically complex cancers retain dependence on an initial oncogenic event and suggest a strategy for identifying inhibitors of STI-571 resistance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gorre, M E -- Mohammed, M -- Ellwood, K -- Hsu, N -- Paquette, R -- Rao, P N -- Sawyers, C L -- GM07185/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2001 Aug 3;293(5531):876-80. Epub 2001 Jun 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11423618" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Antineoplastic Agents/metabolism/pharmacology/therapeutic use ; Base Sequence ; Benzamides ; Blast Crisis/genetics ; Cell Line ; Drug Resistance, Neoplasm/genetics ; Fusion Proteins, bcr-abl/*metabolism ; Gene Amplification ; *Genes, abl ; Humans ; Hydrogen Bonding ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*drug therapy/*genetics ; Molecular Sequence Data ; Philadelphia Chromosome ; Phosphorylation ; Piperazines/metabolism/*pharmacology/therapeutic use ; Point Mutation ; Protein Structure, Tertiary ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins c-abl/antagonists & ; inhibitors/chemistry/*genetics/metabolism ; Proto-Oncogene Proteins c-crk ; Pyrimidines/metabolism/*pharmacology/therapeutic use ; Recurrence ; Signal Transduction
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  • 54
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-06-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gottifredi, V -- Prives, C -- New York, N.Y. -- Science. 2001 Jun 8;292(5523):1851-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Columbia University, New York, NY 10027, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11397937" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Cell Cycle ; Cell Line ; Cell Nucleus/*metabolism ; Cysteine Endopeptidases/metabolism ; Cytoplasm/metabolism ; DNA Damage ; Humans ; Multienzyme Complexes/metabolism ; Nuclear Localization Signals ; Nuclear Pore/metabolism ; *Nuclear Proteins ; Phosphorylation ; Proteasome Endopeptidase Complex ; *Protein Sorting Signals ; Proto-Oncogene Proteins/chemistry/metabolism ; Proto-Oncogene Proteins c-mdm2 ; Recombinant Fusion Proteins/metabolism ; Tumor Suppressor Protein p53/chemistry/*metabolism ; Ubiquitins/metabolism ; Ultraviolet Rays
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  • 55
    Publication Date: 2001-09-05
    Description: We show that high doses of salicylates reverse hyperglycemia, hyperinsulinemia, and dyslipidemia in obese rodents by sensitizing insulin signaling. Activation or overexpression of the IkappaB kinase beta (IKKbeta) attenuated insulin signaling in cultured cells, whereas IKKbeta inhibition reversed insulin resistance. Thus, IKKbeta, rather than the cyclooxygenases, appears to be the relevant molecular target. Heterozygous deletion (Ikkbeta+/-) protected against the development of insulin resistance during high-fat feeding and in obese Lep(ob/ob) mice. These findings implicate an inflammatory process in the pathogenesis of insulin resistance in obesity and type 2 diabetes mellitus and identify the IKKbeta pathway as a target for insulin sensitization.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yuan, M -- Konstantopoulos, N -- Lee, J -- Hansen, L -- Li, Z W -- Karin, M -- Shoelson, S E -- AI43477/AI/NIAID NIH HHS/ -- DK45493/DK/NIDDK NIH HHS/ -- DK51729/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2001 Aug 31;293(5535):1673-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11533494" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; Aspirin/administration & dosage/*pharmacology ; Blood Glucose/metabolism ; Cell Line ; Dietary Fats/*administration & dosage ; Gene Deletion ; Gene Targeting ; Glucose Tolerance Test ; I-kappa B Kinase ; Insulin/administration & dosage/blood/*metabolism/pharmacology ; *Insulin Resistance ; Lipids/blood ; Liver/metabolism ; Male ; Mice ; Mice, Obese ; Muscles/metabolism ; Obesity/metabolism/*physiopathology ; Phosphorylation ; Prostaglandin-Endoperoxide Synthases/genetics/metabolism ; Protein-Serine-Threonine Kinases/antagonists & inhibitors/genetics/*metabolism ; Rats ; Rats, Zucker ; Receptor, Insulin/metabolism ; Signal Transduction ; Sodium Salicylate/administration & dosage/*pharmacology ; Tumor Necrosis Factor-alpha/pharmacology
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  • 56
    Publication Date: 2001-06-09
    Description: The p53 protein is present in low amounts in normally growing cells and is activated in response to physiological insults. MDM2 regulates p53 either through inhibiting p53's transactivating function in the nucleus or by targeting p53 degradation in the cytoplasm. We identified a previously unknown nuclear export signal (NES) in the amino terminus of p53, spanning residues 11 to 27 and containing two serine residues phosphorylated after DNA damage, which was required for p53 nuclear export in colloboration with the carboxyl-terminal NES. Serine-15-phosphorylated p53 induced by ultraviolet irradiation was not exported. Thus, DNA damage-induced phosphorylation may achieve optimal p53 activation by inhibiting both MDM2 binding to, and the nuclear export of, p53.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Y -- Xiong, Y -- CA65572/CA/NCI NIH HHS/ -- K01 CA087580/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2001 Jun 8;292(5523):1910-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lineberger Comprehensive Cancer Center, Department of Biochemistry and Biophysics, and Program in Molecular Biology and Biotechnology, University of North Carolina at Chapel Hill, NC 27599-7295, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11397945" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Amino Acid Sequence ; Animals ; Cell Fusion ; Cell Line ; Cell Nucleus/*metabolism ; Cells, Cultured ; Cytoplasm/metabolism ; *DNA Damage ; Mice ; Molecular Sequence Data ; Mutation ; *Nuclear Proteins ; Phosphorylation ; Phosphoserine/metabolism ; *Protein Sorting Signals ; Protein Structure, Tertiary ; Proteins/genetics/metabolism ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins c-mdm2 ; Recombinant Fusion Proteins/metabolism ; Transfection ; Tumor Suppressor Protein p14ARF ; Tumor Suppressor Protein p53/*chemistry/genetics/*metabolism ; Ubiquitins/metabolism ; Ultraviolet Rays
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  • 57
    Publication Date: 2001-03-27
    Description: During its development, a plant shoot progresses from a juvenile to an adult phase of vegetative growth and from a reproductively incompetent to a reproductively competent state. In Arabidopsis, loss-of-function mutations in SQUINT (SQN) reduced the number of juvenile leaves and had subtle effects on inflorescence morphology but had no effect on flowering time or on reproductive competence. SQN encodes the Arabidopsis homolog of cyclophilin 40 (CyP40), a protein found in association with the Hsp90 chaperone complex in yeast, mammals, and plants. Thus, in Arabidopsis, CyP40 is specifically required for the vegetative but not the reproductive maturation of the shoot.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Berardini, T Z -- Bollman, K -- Sun, H -- Poethig, R S -- R01-GM1893-04/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2001 Mar 23;291(5512):2405-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Plant Science Institute, Department of Biology, University of Pennsylvania, Philadelphia, PA 19104-6018, USA. spoethig@sas.upenn.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11264535" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arabidopsis/anatomy & histology/*genetics/*growth & development/physiology ; Carrier Proteins/chemistry/genetics/physiology ; Chromosome Mapping ; *Cyclophilins ; Exons ; Gene Expression Regulation, Plant ; Genes, Plant ; Heat-Shock Proteins/genetics ; Molecular Sequence Data ; Mutation ; Peptidylprolyl Isomerase/chemistry/genetics/physiology ; Phenotype ; Plant Leaves/anatomy & histology/growth & development ; Plant Shoots/growth & development/physiology ; Reproduction ; Sequence Alignment ; Temperature
    Print ISSN: 0036-8075
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  • 58
    Publication Date: 2001-01-06
    Description: Most traditional cytotoxic anticancer agents ablate the rapidly dividing epithelium of the hair follicle and induce alopecia (hair loss). Inhibition of cyclin-dependent kinase 2 (CDK2), a positive regulator of eukaryotic cell cycle progression, may represent a therapeutic strategy for prevention of chemotherapy-induced alopecia (CIA) by arresting the cell cycle and reducing the sensitivity of the epithelium to many cell cycle-active antitumor agents. Potent small-molecule inhibitors of CDK2 were developed using structure-based methods. Topical application of these compounds in a neonatal rat model of CIA reduced hair loss at the site of application in 33 to 50% of the animals. Thus, inhibition of CDK2 represents a potentially useful approach for the prevention of CIA in cancer patients.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Davis, S T -- Benson, B G -- Bramson, H N -- Chapman, D E -- Dickerson, S H -- Dold, K M -- Eberwein, D J -- Edelstein, M -- Frye, S V -- Gampe Jr, R T -- Griffin, R J -- Harris, P A -- Hassell, A M -- Holmes, W D -- Hunter, R N -- Knick, V B -- Lackey, K -- Lovejoy, B -- Luzzio, M J -- Murray, D -- Parker, P -- Rocque, W J -- Shewchuk, L -- Veal, J M -- Walker, D H -- Kuyper, L F -- New York, N.Y. -- Science. 2001 Jan 5;291(5501):134-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cancer Biology, Glaxo Wellcome Research and Development, Research Triangle Park, NC 27709, USA. std41085@glaxowellcome.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11141566" target="_blank"〉PubMed〈/a〉
    Keywords: Alopecia/*chemically induced/*prevention & control ; Animals ; Animals, Newborn ; Antineoplastic Agents/*toxicity ; Antineoplastic Combined Chemotherapy Protocols/toxicity ; Apoptosis/drug effects ; *CDC2-CDC28 Kinases ; Cell Cycle/drug effects ; Cell Line ; Cyclin-Dependent Kinase 2 ; Cyclin-Dependent Kinases/*antagonists & inhibitors/metabolism ; Cyclophosphamide/toxicity ; Cytoprotection/drug effects ; DNA/biosynthesis ; Doxorubicin/toxicity ; Drug Design ; Enzyme Inhibitors/chemical synthesis/chemistry/*pharmacology ; Epithelium/drug effects ; Etoposide/toxicity ; Hair Follicle/cytology/*drug effects ; Humans ; Indoles/chemical synthesis/chemistry/*pharmacology ; Mice ; Mice, SCID ; Phosphorylation ; Protein-Serine-Threonine Kinases/*antagonists & inhibitors/metabolism ; Rats ; Retinoblastoma Protein/metabolism ; Scalp/transplantation ; Sulfonamides/chemical synthesis/chemistry/*pharmacology ; Transplantation, Heterologous
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  • 59
    Publication Date: 2001-12-01
    Description: Heterotrimeric GTP-binding proteins (G proteins) control cellular functions by transducing signals from the outside to the inside of cells. Regulator of G protein signaling (RGS) proteins are key modulators of the amplitude and duration of G protein-mediated signaling through their ability to serve as guanosine triphosphatase-activating proteins (GAPs). We have identified RGS-PX1, a Galpha(s)-specific GAP. The RGS domain of RGS-PX1 specifically interacted with Galpha(s), accelerated its GTP hydrolysis, and attenuated Galpha(s)-mediated signaling. RGS-PX1 also contains a Phox (PX) domain that resembles those in sorting nexin (SNX) proteins. Expression of RGS-PX1 delayed lysosomal degradation of the EGF receptor. Because of its bifunctional role as both a GAP and a SNX, RGS-PX1 may link heterotrimeric G protein signaling and vesicular trafficking.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zheng, B -- Ma, Y C -- Ostrom, R S -- Lavoie, C -- Gill, G N -- Insel, P A -- Huang, X Y -- Farquhar, M G -- AG14563/AG/NIA NIH HHS/ -- CA58689/CA/NCI NIH HHS/ -- DK17780/DK/NIDDK NIH HHS/ -- GM56904/GM/NIGMS NIH HHS/ -- HL53773/HL/NHLBI NIH HHS/ -- HL63885/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2001 Nov 30;294(5548):1939-42.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093-0651, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11729322" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenergic beta-2 Receptor Agonists ; Amino Acid Sequence ; Animals ; COS Cells ; Carrier Proteins/chemistry/*metabolism ; Cattle ; Cell Line ; Cyclic AMP/metabolism ; Endosomes/chemistry/metabolism ; GTP-Binding Protein alpha Subunits, Gs/antagonists & inhibitors/*metabolism ; GTPase-Activating Proteins/chemistry/*metabolism ; Guanosine Triphosphate/metabolism ; Humans ; Mitogen-Activated Protein Kinases/metabolism ; Molecular Sequence Data ; Protein Binding ; Protein Interaction Mapping ; Protein Structure, Tertiary ; Protein Transport ; RGS Proteins/chemistry/*metabolism ; Receptor, Epidermal Growth Factor/metabolism ; Receptors, Adrenergic, beta-2/genetics/metabolism ; Sequence Alignment ; Signal Transduction ; Sorting Nexins ; Substrate Specificity ; *Vesicular Transport Proteins
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  • 60
    Publication Date: 2001-08-04
    Description: The development of resistance is the main threat to the long-term use of toxins from Bacillus thuringiensis (Bt) in transgenic plants. Here we report the cloning of a Bt toxin resistance gene, Caenorhabditis elegans bre-5, which encodes a putative beta-1,3-galactosyltransferase. Lack of bre-5 in the intestine led to resistance to the Bt toxin Cry5B. Wild-type but not bre-5 mutant animals were found to uptake toxin into their gut cells, consistent with bre-5 mutants lacking toxin-binding sites on their apical gut. bre-5 mutants displayed resistance to Cry14A, a Bt toxin lethal to both nematodes and insects; this indicates that resistance by loss of carbohydrate modification is relevant to multiple Bt toxins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Griffitts, J S -- Whitacre, J L -- Stevens, D E -- Aroian, R V -- New York, N.Y. -- Science. 2001 Aug 3;293(5531):860-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11486087" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Bacterial Proteins/metabolism/*toxicity ; *Bacterial Toxins ; Biological Transport ; Caenorhabditis elegans/enzymology/*genetics/metabolism ; *Caenorhabditis elegans Proteins ; Cloning, Molecular ; Digestive System/enzymology/metabolism ; Disorders of Sex Development ; Drug Resistance/genetics ; Endocytosis ; Endotoxins/metabolism/*toxicity ; Feeding Behavior ; Galactosyltransferases/chemistry/*genetics/*metabolism ; Genes, Helminth ; Hemolysin Proteins ; *Insect Proteins ; Molecular Sequence Data ; Mosaicism ; Mutation ; *Pest Control, Biological ; Receptors, Cell Surface/metabolism ; Transformation, Genetic
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  • 61
    Publication Date: 2001-06-02
    Description: The GGAs are a multidomain protein family implicated in protein trafficking between the Golgi and endosomes. Here, the VHS domain of GGA2 was shown to bind to the acidic cluster-dileucine motif in the cytoplasmic tail of the cation-independent mannose 6-phosphate receptor (CI-MPR). Receptors with mutations in this motif were defective in lysosomal enzyme sorting. The hinge domain of GGA2 bound clathrin, suggesting that GGA2 could be a link between cargo molecules and clathrin-coated vesicle assembly. Thus, GGA2 binding to the CI-MPR is important for lysosomal enzyme targeting.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhu, Y -- Doray, B -- Poussu, A -- Lehto, V P -- Kornfeld, S -- R01 CA-08759/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2001 Jun 1;292(5522):1716-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Internal Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11387476" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Vesicular Transport ; Amino Acid Motifs ; Amino Acid Sequence ; Animals ; *Carrier Proteins ; Cations ; Clathrin/metabolism ; Dipeptides/chemistry/metabolism ; L Cells (Cell Line) ; Lysosomes/*enzymology ; Mice ; Molecular Sequence Data ; Mutation ; Protein Sorting Signals ; Protein Structure, Tertiary ; *Protein Transport ; Proteins/chemistry/genetics/*metabolism ; Rats ; Receptor, IGF Type 2/*chemistry/genetics/*metabolism ; Recombinant Fusion Proteins/chemistry/metabolism ; Solubility ; Transcription Factor AP-1/metabolism ; Transport Vesicles/metabolism ; Two-Hybrid System Techniques ; trans-Golgi Network/metabolism
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  • 62
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-06-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thornton, J M -- New York, N.Y. -- Science. 2001 Jun 15;292(5524):2095-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University College Department of Biochemistry and Molecular Biology, London WC1E 6BT, UK. thornton@biochem.ucl.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11408660" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; *Computational Biology ; Computer Simulation ; Databases, Factual ; Evolution, Molecular ; Genome ; *Models, Molecular ; Peptide Library ; *Protein Conformation ; Protein Structure, Tertiary ; Proteins/*chemistry/*physiology ; Proteome ; Sequence Homology, Amino Acid
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  • 63
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-07-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zuk, P A -- New York, N.Y. -- Science. 2001 Jul 13;293(5528):211-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11452974" target="_blank"〉PubMed〈/a〉
    Keywords: Adipocytes/*cytology ; Cell Differentiation ; Cell Line ; Hematopoietic Stem Cells ; Humans ; Lipectomy ; Mesoderm/cytology ; Research ; *Stem Cells
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  • 64
    Publication Date: 2001-08-18
    Description: B cell homeostasis has been shown to critically depend on BAFF, the B cell activation factor from the tumor necrosis factor (TNF) family. Although BAFF is already known to bind two receptors, BCMA and TACI, we have identified a third receptor for BAFF that we have termed BAFF-R. BAFF-R binding appears to be highly specific for BAFF, suggesting a unique role for this ligand-receptor interaction. Consistent with this, the BAFF-R locus is disrupted in A/WySnJ mice, which display a B cell phenotype qualitatively similar to that of the BAFF-deficient mice. Thus, BAFF-R appears to be the principal receptor for BAFF-mediated mature B cell survival.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thompson, J S -- Bixler, S A -- Qian, F -- Vora, K -- Scott, M L -- Cachero, T G -- Hession, C -- Schneider, P -- Sizing, I D -- Mullen, C -- Strauch, K -- Zafari, M -- Benjamin, C D -- Tschopp, J -- Browning, J L -- Ambrose, C -- New York, N.Y. -- Science. 2001 Sep 14;293(5537):2108-11. Epub 2001 Aug 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biogen, 12 Cambridge Center, Cambridge, MA 02142, USA., The Institute of Biochemistry, University of Lausanne, CH-1066, Epalinges, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11509692" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; B-Cell Activating Factor ; B-Cell Activation Factor Receptor ; B-Cell Maturation Antigen ; B-Lymphocytes/immunology/metabolism/*physiology ; Cell Line ; Chromosome Mapping ; Chromosomes, Human, Pair 22 ; Cloning, Molecular ; Homeostasis ; Humans ; Ligands ; Lymphoid Tissue/metabolism ; Male ; Membrane Proteins/*metabolism ; Mice ; Mice, Inbred A ; Mice, Inbred C57BL ; Molecular Sequence Data ; RNA, Messenger/chemistry/genetics/metabolism ; Receptors, Tumor Necrosis Factor/chemistry/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; Transfection ; Transmembrane Activator and CAML Interactor Protein ; Tumor Necrosis Factor-alpha/*metabolism
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  • 65
    Publication Date: 2001-09-05
    Description: The developmental signaling functions of cell surface heparan sulfate proteoglycans (HSPGs) are dependent on their sulfation states. Here, we report the identification of QSulf1, the avian ortholog of an evolutionarily conserved protein family related to heparan-specific N-acetyl glucosamine sulfatases. QSulf1 expression is induced by Sonic hedgehog in myogenic somite progenitors in quail embryos and is required for the activation of MyoD, a Wnt-induced regulator of muscle specification. QSulf1 is localized on the cell surface and regulates heparan-dependent Wnt signaling in C2C12 myogenic progenitor cells through a mechanism that requires its catalytic activity, providing evidence that QSulf1 regulates Wnt signaling through desulfation of cell surface HSPGs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dhoot, G K -- Gustafsson, M K -- Ai, X -- Sun, W -- Standiford, D M -- Emerson , C P Jr -- New York, N.Y. -- Science. 2001 Aug 31;293(5535):1663-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Basic Veterinary Sciences, The Royal Veterinary College, University of London, Royal College Street, London NW1 OTU, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11533491" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; *Body Patterning ; CHO Cells ; Cell Membrane/metabolism ; Cells, Cultured ; Cloning, Molecular ; Coculture Techniques ; Cricetinae ; Embryo, Nonmammalian/metabolism ; Embryonic Development ; Hedgehog Proteins ; Heparan Sulfate Proteoglycans/*metabolism ; Heparin/metabolism/pharmacology ; Heparitin Sulfate/metabolism ; Molecular Sequence Data ; Muscles/cytology/*embryology/metabolism ; Mutation ; MyoD Protein/genetics/metabolism ; Oligonucleotides, Antisense ; Proto-Oncogene Proteins/*metabolism ; Quail/*embryology ; Recombinant Fusion Proteins/metabolism ; Sequence Alignment ; *Signal Transduction ; Somites/metabolism ; Stem Cells/*metabolism ; Sulfatases/chemistry/genetics/*metabolism ; Trans-Activators/genetics/metabolism ; Transfection ; Wnt Proteins ; *Zebrafish Proteins
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  • 66
    Publication Date: 2001-06-30
    Description: The pollen extracellular matrix contains proteins mediating species specificity and components needed for efficient pollination. We identified all proteins 〉10 kilodaltons in the Arabidopsis pollen coating and showed that most of the corresponding genes reside in two genomic clusters. One cluster encodes six lipases, whereas the other contains six lipid-binding oleosin genes, including GRP17, a gene that promotes efficient pollination. Individual oleosins exhibit extensive divergence between ecotypes, but the entire cluster remains intact. Analysis of the syntenic region in Brassica oleracea revealed even greater divergence, but a similar clustering of the genes. Such allelic flexibility may promote speciation in plants.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mayfield, J A -- Fiebig, A -- Johnstone, S E -- Preuss, D -- New York, N.Y. -- Science. 2001 Jun 29;292(5526):2482-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11431566" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Motifs ; Amino Acid Sequence ; Arabidopsis/chemistry/*genetics ; *Arabidopsis Proteins ; Brassica/chemistry/genetics ; Expressed Sequence Tags ; Genes, Plant ; Genetic Variation ; Genome, Plant ; Lipase/*chemistry/genetics ; Molecular Sequence Data ; *Multigene Family ; Phosphotransferases/chemistry/genetics ; Plant Proteins/*chemistry/genetics ; Pollen/*chemistry ; Protein Structure, Tertiary ; *Proteome ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Alignment
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  • 67
    Publication Date: 2001-02-07
    Description: The disulfide reducing enzymes glutathione reductase and thioredoxin reductase are highly conserved among bacteria, fungi, worms, and mammals. These proteins maintain intracellular redox homeostasis to protect the organism from oxidative damage. Here we demonstrate the absence of glutathione reductase in Drosophila melanogaster, identify a new type of thioredoxin reductase, and provide evidence that a thioredoxin system supports GSSG reduction. Our data suggest that antioxidant defense in Drosophila, and probably in related insects, differs fundamentally from that in other organisms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kanzok, S M -- Fechner, A -- Bauer, H -- Ulschmid, J K -- Muller, H M -- Botella-Munoz, J -- Schneuwly, S -- Schirmer, R -- Becker, K -- New York, N.Y. -- Science. 2001 Jan 26;291(5504):643-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center of Biochemistry, Im Neuenheimer Feld 328, Heidelberg University, D-69120 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11158675" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Binding Sites ; Drosophila melanogaster/*enzymology/genetics/metabolism ; Genes, Insect ; Glutathione/*metabolism ; Glutathione Disulfide/metabolism ; Glutathione Reductase/*metabolism ; Humans ; Kinetics ; Molecular Sequence Data ; Mutation ; NADP/metabolism ; Oxidation-Reduction ; Sequence Alignment ; Species Specificity ; Substrate Specificity ; Thioredoxin-Disulfide Reductase/antagonists & ; inhibitors/chemistry/*genetics/*metabolism
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  • 68
    Publication Date: 2001-11-03
    Description: The bacterial macrolide rapamycin is an efficacious anticancer agent against solid tumors. In a hypoxic environment, the increase in mass of solid tumors is dependent on the recruitment of mitogens and nutrients. When nutrient concentrations change, particularly those of essential amino acids, the mammalian Target of Rapamycin (mTOR) functions in regulatory pathways that control ribosome biogenesis and cell growth. In bacteria, ribosome biogenesis is independently regulated by amino acids and adenosine triphosphate (ATP). Here we demonstrate that the mTOR pathway is influenced by the intracellular concentration of ATP, independent of the abundance of amino acids, and that mTOR itself is an ATP sensor.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dennis, P B -- Jaeschke, A -- Saitoh, M -- Fowler, B -- Kozma, S C -- Thomas, G -- New York, N.Y. -- Science. 2001 Nov 2;294(5544):1102-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058, Basel, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11691993" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing ; Adenosine Triphosphate/*metabolism ; Amino Acids/metabolism ; Androstadienes/pharmacology ; Carrier Proteins/metabolism ; Cell Line ; Deoxyglucose/pharmacology ; Enzyme Activation ; Homeostasis ; Humans ; Insulin/pharmacology ; Kinetics ; Phosphoproteins/metabolism ; Phosphorylation ; Protein Kinases/*metabolism ; RNA, Transfer, Amino Acyl/metabolism ; Recombinant Fusion Proteins/metabolism ; Ribosomal Protein S6 Kinases/antagonists & inhibitors/metabolism ; Ribosomes/metabolism ; Rotenone/pharmacology ; Signal Transduction ; Sirolimus/pharmacology ; TOR Serine-Threonine Kinases
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  • 69
    Publication Date: 2001-09-08
    Description: Bcl-2 family members bearing only the BH3 domain are essential inducers of apoptosis. We identified a BH3-only protein, Bmf, and show that its BH3 domain is required both for binding to prosurvival Bcl-2 proteins and for triggering apoptosis. In healthy cells, Bmf is sequestered to myosin V motors by association with dynein light chain 2. Certain damage signals, such as loss of cell attachment (anoikis), unleash Bmf, allowing it to translocate and bind prosurvival Bcl-2 proteins. Thus, at least two mammalian BH3-only proteins, Bmf and Bim, function to sense intracellular damage by their localization to distinct cytoskeletal structures.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Puthalakath, H -- Villunger, A -- O'Reilly, L A -- Beaumont, J G -- Coultas, L -- Cheney, R E -- Huang, D C -- Strasser, A -- CA 80188/CA/NCI NIH HHS/ -- R29 DC003299/DC/NIDCD NIH HHS/ -- New York, N.Y. -- Science. 2001 Sep 7;293(5536):1829-32.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Walter and Eliza Hall Institute of Medical Research, Melbourne, P.O. Royal Melbourne Hospital, 3050 VIC, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11546872" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptor Proteins, Signal Transducing ; Amino Acid Sequence ; Animals ; *Anoikis ; Apoptosis Regulatory Proteins ; Calmodulin-Binding Proteins/*metabolism ; Carrier Proteins/*chemistry/genetics/*metabolism ; Cell Line ; Cytoskeleton/metabolism ; *Drosophila Proteins ; Dyneins ; Gene Expression Profiling ; Humans ; *Membrane Proteins ; Mice ; Molecular Motor Proteins/*metabolism ; Molecular Sequence Data ; Mutation ; Myeloid Cell Leukemia Sequence 1 Protein ; *Myosin Type V ; Neoplasm Proteins/genetics/metabolism ; Nerve Tissue Proteins/*metabolism ; Protein Binding ; Protein Structure, Tertiary ; Protein Transport ; *Proto-Oncogene Proteins ; Proto-Oncogene Proteins c-bcl-2/chemistry/genetics/metabolism ; RNA, Messenger/analysis/genetics ; Transfection ; Two-Hybrid System Techniques
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  • 70
    Publication Date: 2001-05-12
    Description: Epigenetic silenced alleles of the Arabidopsis SUPERMAN locus (the clark kent alleles) are associated with dense hypermethylation at noncanonical cytosines (CpXpG and asymmetric sites, where X = A, T, C, or G). A genetic screen for suppressors of a hypermethylated clark kent mutant identified nine loss-of-function alleles of CHROMOMETHYLASE3 (CMT3), a novel cytosine methyltransferase homolog. These cmt3 mutants display a wild-type morphology but exhibit decreased CpXpG methylation of the SUP gene and of other sequences throughout the genome. They also show reactivated expression of endogenous retrotransposon sequences. These results show that a non-CpG DNA methyltransferase is responsible for maintaining epigenetic gene silencing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lindroth, A M -- Cao, X -- Jackson, J P -- Zilberman, D -- McCallum, C M -- Henikoff, S -- Jacobsen, S E -- GM07104/GM/NIGMS NIH HHS/ -- GM07185/GM/NIGMS NIH HHS/ -- GM29009/GM/NIGMS NIH HHS/ -- GM60398/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2001 Jun 15;292(5524):2077-80. Epub 2001 May 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11349138" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Sequence ; Arabidopsis/*genetics/metabolism ; *Arabidopsis Proteins ; Base Sequence ; Chromosome Mapping ; Cloning, Molecular ; CpG Islands ; Crosses, Genetic ; Cytosine/metabolism ; *DNA Methylation ; DNA-Cytosine Methylases/chemistry/*genetics/*metabolism ; Dinucleoside Phosphates/metabolism ; Gene Expression Regulation, Plant ; *Gene Silencing ; Genes, Plant ; Molecular Sequence Data ; Mutagenesis ; Oligonucleotides/*metabolism ; Phenotype ; Protein Structure, Tertiary ; Retroelements ; Transcription Factors/*genetics
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  • 71
    Publication Date: 2001-02-24
    Description: Human cytomegalovirus infects vascular tissues and has been associated with atherogenesis and coronary restenosis. Although established laboratory strains of human cytomegalovirus have lost the ability to grow on vascular endothelial cells, laboratory strains of murine cytomegalovirus retain this ability. With the use of a forward-genetic procedure involving random transposon mutagenesis and rapid phenotypic screening, we identified a murine cytomegalovirus gene governing endothelial cell tropism. This gene, M45, shares sequence homology to ribonucleotide reductase genes. Endothelial cells infected with M45-mutant viruses rapidly undergo apoptosis, suggesting that a viral strategy to evade destruction by cellular apoptosis is indispensable for viral growth in endothelial cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brune, W -- Menard, C -- Heesemann, J -- Koszinowski, U H -- New York, N.Y. -- Science. 2001 Jan 12;291(5502):303-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA. wbrune@princeton.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11209080" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Animals ; Apoptosis ; Base Sequence ; Cell Line ; Cytopathogenic Effect, Viral ; DNA Transposable Elements ; Endothelium, Vascular/*cytology/*virology ; Fibroblasts/virology ; Frameshift Mutation ; Gene Library ; *Genes, Viral ; Mice ; Molecular Sequence Data ; Muromegalovirus/*genetics/growth & development/*physiology ; Mutagenesis, Insertional ; Open Reading Frames ; Phenotype ; Ribonucleotide Reductases/*genetics/physiology ; *Viral Proteins ; Virus Replication
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  • 72
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-06-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vogel, G -- New York, N.Y. -- Science. 2001 Jun 8;292(5523):1822.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11397926" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animal Experimentation ; Animals ; *Bioethics ; Cell Line ; *Embryo Research ; Embryo, Mammalian/*cytology ; Humans ; *Macaca mulatta ; *Research ; *Stem Cells
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  • 73
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-05-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vogel, G -- New York, N.Y. -- Science. 2001 Apr 20;292(5516):429.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11330290" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Culture Techniques ; Cell Differentiation ; Cell Line ; Collagen ; Culture Media, Conditioned ; Drug Combinations ; Epithelial Cells/cytology/metabolism ; Genetic Engineering ; Green Fluorescent Proteins ; Hepatocytes/cytology/metabolism ; Humans ; Laminin ; Luminescent Proteins/biosynthesis ; Mice ; Neurons/cytology/metabolism ; Proteoglycans ; Stem Cell Transplantation ; Stem Cells/*cytology
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  • 74
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-11-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ferber, D -- New York, N.Y. -- Science. 2001 Nov 23;294(5547):1639.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11721030" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; DNA/chemistry/genetics/metabolism ; DNA Repair/drug effects/*genetics ; Dependovirus/genetics ; Gene Targeting/*methods ; Genetic Diseases, Inborn/*genetics/*therapy ; Genetic Therapy/*methods/trends ; Humans ; Mice ; Mutation/*genetics ; Oligonucleotides/chemistry/genetics/metabolism/pharmacology ; Point Mutation/genetics ; Recombination, Genetic/drug effects/genetics ; Sequence Homology, Nucleic Acid
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  • 75
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-08-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holden, C -- New York, N.Y. -- Science. 2001 Aug 10;293(5532):1025.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11498550" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; Cloning, Organism/*legislation & jurisprudence ; Embryo Research ; Embryo, Mammalian/*cytology ; Humans ; Politics ; *Research ; *Stem Cells ; United States
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  • 76
    Publication Date: 2001-10-27
    Description: ErbB-4 is a transmembrane receptor tyrosine kinase that regulates cell proliferation and differentiation. After binding of its ligand heregulin (HRG) or activation of protein kinase C (PKC) by 12-O-tetradecanoylphorbol-13-acetate (TPA), the ErbB-4 ectodomain is cleaved by a metalloprotease. We now report a subsequent cleavage by gamma-secretase that releases the ErbB-4 intracellular domain from the membrane and facilitates its translocation to the nucleus. gamma-Secretase cleavage was prevented by chemical inhibitors or a dominant negative presenilin. Inhibition of gamma-secretase also prevented growth inhibition by HRG. gamma-Secretase cleavage of ErbB-4 may represent another mechanism for receptor tyrosine kinase-mediated signaling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ni, C Y -- Murphy, M P -- Golde, T E -- Carpenter, G -- CA24071/CA/NCI NIH HHS/ -- CA68485/CA/NCI NIH HHS/ -- DK20593/DK/NIDDK NIH HHS/ -- NS39072/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2001 Dec 7;294(5549):2179-81. Epub 2001 Oct 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11679632" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Amino Acid Sequence ; Amyloid Precursor Protein Secretases ; Animals ; Aspartic Acid Endopeptidases ; COS Cells ; Carbamates/pharmacology ; Cell Division/drug effects ; Cell Line ; Cell Membrane/metabolism ; Cell Nucleus/*metabolism ; Cytoplasm/metabolism ; Dipeptides/pharmacology ; Endopeptidases/*metabolism ; Fatty Acids, Unsaturated/pharmacology ; Humans ; Membrane Proteins/genetics/metabolism ; Metalloendopeptidases/metabolism ; Mice ; Molecular Sequence Data ; Mutation ; Neuregulin-1/pharmacology ; Presenilin-1 ; Protease Inhibitors/pharmacology ; Protein Structure, Tertiary ; Receptor, Epidermal Growth Factor/chemistry/*metabolism ; Receptor, ErbB-4 ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; Tetradecanoylphorbol Acetate/pharmacology ; Transcriptional Activation ; Tumor Cells, Cultured
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  • 77
    Publication Date: 2001-02-27
    Description: Bag (Bcl2-associated athanogene) domains occur in a class of cofactors of the eukaryotic chaperone 70-kilodalton heat shock protein (Hsp70) family. Binding of the Bag domain to the Hsp70 adenosine triphosphatase (ATPase) domain promotes adenosine 5'-triphosphate-dependent release of substrate from Hsp70 in vitro. In a 1.9 angstrom crystal structure of a complex with the ATPase of the 70-kilodalton heat shock cognate protein (Hsc70), the Bag domain forms a three-helix bundle, inducing a conformational switch in the ATPase that is incompatible with nucleotide binding. The same switch is observed in the bacterial Hsp70 homolog DnaK upon binding of the structurally unrelated nucleotide exchange factor GrpE. Thus, functional convergence has allowed proteins with different architectures to trigger a conserved conformational shift in Hsp70 that leads to nucleotide exchange.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sondermann, H -- Scheufler, C -- Schneider, C -- Hohfeld, J -- Hartl, F U -- Moarefi, I -- New York, N.Y. -- Science. 2001 Feb 23;291(5508):1553-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular Biochemistry, Max-Planck-Institut fur Biochemie, D-82152 Martinsried, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11222862" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Diphosphate/metabolism ; Adenosine Triphosphatases/*chemistry/*metabolism ; Adenosine Triphosphate/metabolism ; Amino Acid Sequence ; Animals ; Bacterial Proteins/chemistry/metabolism ; Carrier Proteins/*chemistry/*metabolism ; Cattle ; Crystallography, X-Ray ; DNA-Binding Proteins ; *Escherichia coli Proteins ; Evolution, Molecular ; HSC70 Heat-Shock Proteins ; HSP70 Heat-Shock Proteins/*chemistry/*metabolism ; Heat-Shock Proteins/chemistry/metabolism ; Humans ; Hydrolysis ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Protein Isoforms ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Transcription Factors
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  • 78
    Publication Date: 2001-04-28
    Description: Embryonic stem (ES) cells are fully pluripotent in that they can differentiate into all cell types, including gametes. We have derived 35 ES cell lines via nuclear transfer (ntES cell lines) from adult mouse somatic cells of inbred, hybrid, and mutant strains. ntES cells contributed to an extensive variety of cell types, including dopaminergic and serotonergic neurons in vitro and germ cells in vivo. Cloning by transfer of ntES cell nuclei could result in normal development of fertile adults. These studies demonstrate the full pluripotency of ntES cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wakayama, T -- Tabar, V -- Rodriguez, I -- Perry, A C -- Studer, L -- Mombaerts, P -- New York, N.Y. -- Science. 2001 Apr 27;292(5517):740-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Rockefeller University, New York, NY 10021, USA. teru@advancedcell.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11326103" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blastocyst/*cytology ; *Cell Differentiation ; Cell Line ; Cell Lineage ; Chimera ; Cloning, Organism ; Crosses, Genetic ; Dopamine/metabolism ; Embryo Transfer ; Female ; Germ Cells/*cytology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Mice, Inbred ICR ; Mice, Nude ; Neurons/*cytology ; *Nuclear Transfer Techniques ; Serotonin/metabolism ; Stem Cells/*cytology
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  • 79
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-12-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Catterall, W A -- New York, N.Y. -- Science. 2001 Dec 14;294(5550):2306-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of Washington, Seattle, WA 98195, USA. wcatt@u.washington.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11743190" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Bacillus/*chemistry/metabolism ; Bacterial Proteins/antagonists & inhibitors/chemistry/*metabolism ; Calcium Channels/chemistry/metabolism ; Ion Channel Gating ; Ion Transport ; Membrane Potentials ; Potassium Channel Blockers ; Potassium Channels/chemistry/metabolism ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Sodium/*metabolism ; Sodium Channel Blockers ; Sodium Channels/*chemistry/*metabolism ; Static Electricity
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  • 80
    Publication Date: 2001-09-05
    Description: Cardiac valve formation is a complex process that involves cell signaling events between the myocardial and endocardial layers of the heart across an elaborate extracellular matrix. These signals lead to marked morphogenetic movements and transdifferentiation of the endocardial cells at chamber boundaries. Here we identify the genetic defect in zebrafish jekyll mutants, which are deficient in the initiation of heart valve formation. The jekyll mutation disrupts a homolog of Drosophila Sugarless, a uridine 5'-diphosphate (UDP)-glucose dehydrogenase required for heparan sulfate, chondroitin sulfate, and hyaluronic acid production. The atrioventricular border cells do not differentiate from their neighbors in jekyll mutants, suggesting that Jekyll is required in a cell signaling event that establishes a boundary between the atrium and ventricle.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Walsh, E C -- Stainier, D Y -- HL54737/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2001 Aug 31;293(5535):1670-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, Programs in Developmental Biology, Genetics and Human Genetics, University of California, San Francisco, CA 94143-0448, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11533493" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antisense Elements (Genetics) ; Body Patterning ; Bone Morphogenetic Proteins/genetics ; Endocardium/embryology/metabolism ; Female ; Gene Expression ; Glycosaminoglycans/metabolism ; Heart/*embryology ; Heart Valves/cytology/*embryology/enzymology/metabolism ; Male ; Molecular Sequence Data ; Morphogenesis ; Mutation ; Myocardium/cytology/metabolism ; Phenotype ; Physical Chromosome Mapping ; Signal Transduction ; Uridine Diphosphate Glucose Dehydrogenase/*genetics/*metabolism ; Zebrafish/*embryology/genetics
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  • 81
    Publication Date: 2001-08-04
    Description: One of the most dominant influences in the patterning of multicellular embryos is exerted by the Hedgehog (Hh) family of secreted signaling proteins. Here, we identify a segment polarity gene in Drosophila melanogaster, skinny hedgehog (ski), and show that its product is required in Hh-expressing cells for production of appropriate signaling activity in embryos and in the imaginal precursors of adult tissues. The ski gene encodes an apparent acyltransferase, and we provide genetic and biochemical evidence that Hh proteins from ski mutant cells retain carboxyl-terminal cholesterol modification but lack amino-terminal palmitate modification. Our results suggest that ski encodes an enzyme that acts within the secretory pathway to catalyze amino-terminal palmitoylation of Hh, and further demonstrate that this lipid modification is required for the embryonic and larval patterning activities of the Hh signal.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chamoun, Z -- Mann, R K -- Nellen, D -- von Kessler, D P -- Bellotto, M -- Beachy, P A -- Basler, K -- New York, N.Y. -- Science. 2001 Sep 14;293(5537):2080-4. Epub 2001 Aug 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut fur Molekularbiologie and Zoologisches Institut, Universitat Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11486055" target="_blank"〉PubMed〈/a〉
    Keywords: Acylation ; Acyltransferases/chemistry/*genetics/*metabolism ; Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Body Patterning ; Cholesterol/metabolism ; *Drosophila Proteins ; Drosophila melanogaster/embryology/*genetics/growth & development/metabolism ; Gene Expression ; Genes, Insect ; Hedgehog Proteins ; Insect Proteins/chemistry/genetics/*metabolism ; Molecular Sequence Data ; Mutation ; Palmitic Acid/*metabolism ; Protein Structure, Tertiary ; *Signal Transduction ; Transgenes
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  • 82
    Publication Date: 2001-06-02
    Description: Acetylation of core histone tails plays a fundamental role in transcription regulation. In addition to acetylation, other posttranslational modifications, such as phosphorylation and methylation, occur in core histone tails. Here, we report the purification, molecular identification, and functional characterization of a histone H4-specific methyltransferase PRMT1, a protein arginine methyltransferase. PRMT1 specifically methylates arginine 3 (Arg 3) of H4 in vitro and in vivo. Methylation of Arg 3 by PRMT1 facilitates subsequent acetylation of H4 tails by p300. However, acetylation of H4 inhibits its methylation by PRMT1. Most important, a mutation in the S-adenosyl-l-methionine-binding site of PRMT1 substantially crippled its nuclear receptor coactivator activity. Our finding reveals Arg 3 of H4 as a novel methylation site by PRMT1 and indicates that Arg 3 methylation plays an important role in transcriptional regulation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, H -- Huang, Z Q -- Xia, L -- Feng, Q -- Erdjument-Bromage, H -- Strahl, B D -- Briggs, S D -- Allis, C D -- Wong, J -- Tempst, P -- Zhang, Y -- GM63067-01/GM/NIGMS NIH HHS/ -- P30 CA08748/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2001 Aug 3;293(5531):853-7. Epub 2001 May 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11387442" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Amino Acid Sequence ; Animals ; Arginine/*metabolism ; Binding Sites ; Cell Nucleus/metabolism ; HeLa Cells ; Histones/chemistry/*metabolism ; Humans ; Hydroxamic Acids/pharmacology ; Intracellular Signaling Peptides and Proteins ; Lysine/metabolism ; Methylation ; Methyltransferases/chemistry/genetics/isolation & purification/*metabolism ; Molecular Sequence Data ; Mutation ; Oocytes ; Protein-Arginine N-Methyltransferases ; Receptors, Androgen/*metabolism ; Recombinant Proteins/metabolism ; S-Adenosylmethionine/metabolism ; *Transcriptional Activation ; Xenopus
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  • 83
    Publication Date: 2001-09-08
    Description: Multidrug resistance (MDR) is a serious medical problem and presents a major challenge to the treatment of disease and the development of novel therapeutics. ABC transporters that are associated with multidrug resistance (MDR-ABC transporters) translocate hydrophobic drugs and lipids from the inner to the outer leaflet of the cell membrane. To better elucidate the structural basis for the "flip-flop" mechanism of substrate movement across the lipid bilayer, we have determined the structure of the lipid flippase MsbA from Escherichia coli by x-ray crystallography to a resolution of 4.5 angstroms. MsbA is organized as a homodimer with each subunit containing six transmembrane alpha-helices and a nucleotide-binding domain. The asymmetric distribution of charged residues lining a central chamber suggests a general mechanism for the translocation of substrate by MsbA and other MDR-ABC transporters. The structure of MsbA can serve as a model for the MDR-ABC transporters that confer multidrug resistance to cancer cells and infectious microorganisms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chang, G -- Roth, C B -- GM61905-01/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2001 Sep 7;293(5536):1793-800.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, MB-9, The Scripps Research Institute, La Jolla, CA 92037, USA. gchang@scripps.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11546864" target="_blank"〉PubMed〈/a〉
    Keywords: *ATP-Binding Cassette Transporters ; Adenosine Triphosphate/metabolism ; Amino Acid Sequence ; Bacterial Proteins/*chemistry/genetics/metabolism ; Binding Sites ; Biological Transport ; Crystallography, X-Ray ; Dimerization ; *Drug Resistance, Microbial ; *Drug Resistance, Multiple ; Escherichia coli/*enzymology ; Lipid A/metabolism ; Membrane Proteins/*chemistry/genetics/metabolism ; Models, Molecular ; Molecular Sequence Data ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Sequence Alignment ; Static Electricity ; Structure-Activity Relationship
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  • 84
    Publication Date: 2001-06-26
    Description: Recent studies in bacterial pathogenesis reveal common and contrasting mechanisms of pathogen virulence and host resistance in plant and animal diseases. This review presents recent developments in the study of plant and animal pathogenesis, with respect to bacterial colonization and the delivery of effector proteins to the host. Furthermore, host defense responses in both plants and animals are discussed in relation to mechanisms of pathogen recognition and defense signaling. Future studies will greatly add to our understanding of the molecular events defining host-pathogen interactions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Staskawicz, B J -- Mudgett, M B -- Dangl, J L -- Galan, J E -- New York, N.Y. -- Science. 2001 Jun 22;292(5525):2285-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant and Microbial Biology, University of California at Berkeley, Berkeley, CA 94720, USA. stask@nature.berkeley.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11423652" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Bacteria/genetics/metabolism/*pathogenicity ; Bacterial Infections/immunology/microbiology ; Bacterial Proteins/chemistry/genetics/metabolism ; Genes, Bacterial ; Genes, Plant ; Immunity, Innate ; Molecular Sequence Data ; Plant Diseases/*microbiology ; Plant Proteins/chemistry/genetics/metabolism ; Plants/genetics/metabolism/*microbiology ; Proteins/genetics/metabolism ; Virulence
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  • 85
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-06-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Finlay, B B -- New York, N.Y. -- Science. 2001 Jun 1;292(5522):1665-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biotechnology Laboratory, University of British Columbia, Vancouver, V6T 1Z3, British Columbia, Canada. bfinlay@interchange.ubc.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11387462" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Bacterial Proteins/chemistry/*metabolism ; Bacterial Translocation ; Cadherins/chemistry/genetics/*metabolism ; Carrier Proteins/genetics ; Cell Line ; *Disease Models, Animal ; Fatty Acid-Binding Proteins ; Guinea Pigs ; Humans ; Intestinal Mucosa/cytology/metabolism/*microbiology ; Intestine, Small/cytology/metabolism/microbiology ; Listeria monocytogenes/metabolism/*pathogenicity ; Listeriosis/*microbiology ; Mice ; Mice, Transgenic ; *Neoplasm Proteins ; *Nerve Tissue Proteins ; Promoter Regions, Genetic ; *Tumor Suppressor Proteins ; Virulence
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  • 86
    Publication Date: 2001-09-05
    Description: Cyclin E binds and activates the cyclin-dependent kinase Cdk2 and catalyzes the transition from the G1 phase to the S phase of the cell cycle. The amount of cyclin E protein present in the cell is tightly controlled by ubiquitin-mediated proteolysis. Here we identify the ubiquitin ligase responsible for cyclin E ubiquitination as SCFFbw7 and demonstrate that it is functionally conserved in yeast, flies, and mammals. Fbw7 associates specifically with phosphorylated cyclin E, and SCFFbw7 catalyzes cyclin E ubiquitination in vitro. Depletion of Fbw7 leads to accumulation and stabilization of cyclin E in vivo in human and Drosophila melanogaster cells. Multiple F-box proteins contribute to cyclin E stability in yeast, suggesting an overlap in SCF E3 ligase specificity that allows combinatorial control of cyclin E degradation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Koepp, D M -- Schaefer, L K -- Ye, X -- Keyomarsi, K -- Chu, C -- Harper, J W -- Elledge, S J -- R01 AG011085/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2001 Oct 5;294(5540):173-7. Epub 2001 Aug 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Howard Hughes Medical Institute, 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/11533444" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Breast Neoplasms/genetics/metabolism ; *CDC2-CDC28 Kinases ; *Cell Cycle ; Cell Cycle Proteins/chemistry/genetics/*metabolism ; Cell Line ; Cyclin E/*metabolism ; Cyclin-Dependent Kinase 2 ; Cyclin-Dependent Kinases/metabolism ; Drosophila Proteins ; Drosophila melanogaster ; *F-Box Proteins ; Humans ; Mice ; Molecular Sequence Data ; Peptide Synthases/chemistry/genetics/*metabolism ; Phosphorylation ; Protein-Serine-Threonine Kinases/metabolism ; RNA, Double-Stranded ; Recombinant Fusion Proteins/metabolism ; SKP Cullin F-Box Protein Ligases ; Saccharomyces cerevisiae/genetics/metabolism ; Saccharomyces cerevisiae Proteins ; Sequence Alignment ; Transfection ; Tumor Cells, Cultured ; *Ubiquitin-Protein Ligases ; Ubiquitins/*metabolism
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  • 87
    Publication Date: 2001-07-07
    Description: In the visual system, the establishment of the anteroposterior and dorsoventral axes in the retina and tectum during development is important for topographic retinotectal projection. We identified chick Ventroptin, an antagonist of bone morphogenetic protein 4 (BMP-4), which is mainly expressed in the ventral retina, not only with a ventral high-dorsal low gradient but also with a nasal high-temporal low gradient at later stages. Misexpression of Ventroptin altered expression patterns of several topographic genes in the retina and projection of the retinal axons to the tectum along both axes. Thus, the topographic retinotectal projection appears to be specified by the double-gradient molecule Ventroptin along the two axes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sakuta, H -- Suzuki, R -- Takahashi, H -- Kato, A -- Shintani, T -- Iemura Si -- Yamamoto, T S -- Ueno, N -- Noda, M -- New York, N.Y. -- Science. 2001 Jul 6;293(5527):111-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Molecular Neurobiology, National Institute for Basic Biology, The Graduate University for Advanced Studies, 38 Nishigonaka, Myodaiji-cho, Okazaki 444-8585, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11441185" target="_blank"〉PubMed〈/a〉
    Keywords: Alternative Splicing ; Amino Acid Sequence ; Animals ; Bone Morphogenetic Protein 4 ; Bone Morphogenetic Proteins/*antagonists & inhibitors/genetics/metabolism ; Chick Embryo ; Cloning, Molecular ; Electroporation ; Embryo, Nonmammalian/cytology/metabolism ; Eye Proteins/chemistry/genetics/*metabolism ; *Gene Expression Regulation, Developmental ; Gene Library ; Humans ; In Situ Hybridization ; Mice ; Microinjections ; Molecular Sequence Data ; *Morphogenesis ; Nerve Tissue Proteins ; Precipitin Tests ; Protein Binding ; Protein Isoforms/chemistry/genetics/metabolism ; RNA, Messenger/analysis/genetics ; Retina/*embryology/*metabolism ; Sequence Alignment ; Surface Plasmon Resonance ; Xenopus Proteins ; Xenopus laevis/embryology/metabolism
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  • 88
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-03-07
    Description: Human immunodeficiency virus type-1 (HIV-1) membrane fusion is promoted by the formation of a trimer-of-hairpins structure that brings the amino- and carboxyl-terminal regions of the gp41 envelope glycoprotein ectodomain into close proximity. Peptides derived from the carboxyl-terminal region (called C-peptides) potently inhibit HIV-1 entry by binding to the gp41 amino-terminal region. To test the converse of this inhibitory strategy, we designed a small protein, denoted 5-Helix, that binds the C-peptide region of gp41. The 5-Helix protein displays potent (nanomolar) inhibitory activity against diverse HIV-1 variants and may serve as the basis for a new class of antiviral agents. The inhibitory activity of 5-Helix also suggests a strategy for generating an HIV-1 neutralizing antibody response that targets the carboxyl-terminal region of the gp41 ectodomain.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Root, M J -- Kay, M S -- Kim, P S -- P01 GM56552/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2001 Feb 2;291(5505):884-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. kimadmin@wi.mit.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11229405" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; *Anti-HIV Agents/chemistry/immunology/metabolism/pharmacology ; Carrier Proteins/*chemistry/metabolism/*pharmacology ; Cell Line ; *Drug Design ; Giant Cells/drug effects ; HIV Antibodies/immunology ; HIV Envelope Protein gp41/chemistry/*metabolism ; HIV-1/*drug effects/physiology ; Humans ; Membrane Fusion/*drug effects ; Molecular Sequence Data ; Neutralization Tests ; Peptide Fragments/chemistry/immunology/metabolism ; *Peptides ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Tumor Cells, Cultured
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  • 89
    Publication Date: 2002-02-02
    Description: In bacteria, promoter recognition depends on the RNA polymerase sigma subunit, which combines with the catalytically proficient RNA polymerase core to form the holoenzyme. The major class of bacterial promoters is defined by two conserved elements (the -10 and -35 elements, which are 10 and 35 nucleotides upstream of the initiation point, respectively) that are contacted by sigma in the holoenzyme. We show that recognition of promoters of this class depends on the "flexible flap" domain of the RNA polymerase beta subunit. The flap interacts with conserved region 4 of sigma and triggers a conformational change that moves region 4 into the correct position for interaction with the -35 element. Because the flexible flap is evolutionarily conserved, this domain may facilitate promoter recognition by specificity factors in eukaryotes as well.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kuznedelov, Konstantin -- Minakhin, Leonid -- Niedziela-Majka, Anita -- Dove, Simon L -- Rogulja, Dragana -- Nickels, Bryce E -- Hochschild, Ann -- Heyduk, Tomasz -- Severinov, Konstantin -- GM44025/GM/NIGMS NIH HHS/ -- GM50514/GM/NIGMS NIH HHS/ -- R01 GM044025/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2002 Feb 1;295(5556):855-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Waksman Institute, Department of Genetics, Rutgers University, Piscataway, NJ 08854, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11823642" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Amino Acid Sequence ; Bacterial Proteins/chemistry/genetics/*metabolism ; DNA, Bacterial/genetics/metabolism ; DNA-Directed RNA Polymerases/chemistry/genetics/*metabolism ; Energy Transfer ; Escherichia coli/*enzymology/genetics ; Holoenzymes/chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; *Promoter Regions, Genetic ; Protein Conformation ; Protein Structure, Tertiary ; Recombinant Fusion Proteins/chemistry/metabolism ; Sigma Factor/chemistry/genetics/*metabolism ; *Transcription, Genetic ; Two-Hybrid System Techniques
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  • 90
    Publication Date: 2002-07-06
    Description: The enzymatic conjugation of arginine to the N-termini of proteins is a part of the ubiquitin-dependent N-end rule pathway of protein degradation. In mammals, three N-terminal residues-aspartate, glutamate, and cysteine-are substrates for arginylation. The mouse ATE1 gene encodes a family of Arg-tRNA-protein transferases (R-transferases) that mediate N-terminal arginylation. We constructed ATE1-lacking mouse strains and found that ATE1-/- embryos die with defects in heart development and in angiogenic remodeling of the early vascular plexus. Through biochemical analyses, we show that N-terminal cysteine, in contrast to N-terminal aspartate and glutamate, is oxidized before its arginylation by R-transferase, suggesting that the arginylation branch of the N-end rule pathway functions as an oxygen sensor.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kwon, Yong Tae -- Kashina, Anna S -- Davydov, Ilia V -- Hu, Rong-Gui -- An, Jee Young -- Seo, Jai Wha -- Du, Fangyong -- Varshavsky, Alexander -- GM31530/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2002 Jul 5;297(5578):96-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology, 147-75, 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/12098698" target="_blank"〉PubMed〈/a〉
    Keywords: Alkylation ; Aminoacyltransferases/*genetics/*metabolism ; Animals ; Aorta/embryology ; Arginine/*metabolism ; Aspartic Acid/metabolism ; Blood Vessels/*embryology ; Cell Line ; Cysteic Acid/metabolism ; Cysteine/metabolism ; Female ; Glutamic Acid/metabolism ; Heart/*embryology ; Heart Defects, Congenital/embryology ; Heart Septal Defects/embryology ; Hypoxia-Inducible Factor 1, alpha Subunit ; Male ; Mice ; Mice, Inbred C57BL ; Neovascularization, Physiologic ; Oxidation-Reduction ; Proteins/*metabolism ; Pulmonary Artery/embryology ; RGS Proteins/metabolism ; Recombinant Proteins/metabolism ; Sulfinic Acids/metabolism ; Transcription Factors/metabolism ; Transfection
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  • 91
    Publication Date: 2001-02-13
    Description: We cloned and characterized a protein kinase and ion channel, TRP-PLIK. As part of the long transient receptor potential channel subfamily implicated in control of cell division, it is a protein that is both an ion channel and a protein kinase. TRP-PLIK phosphorylated itself, displayed a wide tissue distribution, and, when expressed in CHO-K1 cells, constituted a nonselective, calcium-permeant, 105-picosiemen, steeply outwardly rectifying conductance. The zinc finger containing alpha-kinase domain was functional. Inactivation of the kinase activity by site-directed mutagenesis and the channel's dependence on intracellular adenosine triphosphate (ATP) demonstrated that the channel's kinase activity is essential for channel function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Runnels, L W -- Yue, L -- Clapham, D E -- New York, N.Y. -- Science. 2001 Feb 9;291(5506):1043-7. Epub 2001 Jan 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Cardiology, Department of Neurobiology, Harvard Medical School, 1309 Enders Building, 320 Longwood Avenue, Children's Hospital, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11161216" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Amino Acid Motifs ; Amino Acid Sequence ; Animals ; CHO Cells ; Calcium/metabolism ; Catalytic Domain ; Cations/metabolism ; Cell Line ; Cricetinae ; DNA, Complementary ; Electric Conductivity ; Humans ; Ion Channels/chemistry/*genetics/*metabolism ; *Membrane Proteins ; Mice ; Molecular Sequence Data ; Mutation ; Myelin Basic Protein/metabolism ; Patch-Clamp Techniques ; Phosphorylation ; Protein Kinases/chemistry/*genetics/*metabolism ; Protein-Serine-Threonine Kinases ; Rats ; Recombinant Fusion Proteins/chemistry/metabolism ; TRPM Cation Channels ; Transfection ; Two-Hybrid System Techniques ; Type C Phospholipases/metabolism
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  • 92
    Publication Date: 2001-07-07
    Description: Clock:BMAL1 and NPAS2:BMAL1 are heterodimeric transcription factors that control gene expression as a function of the light-dark cycle. Although built to fluctuate at or near a 24-hour cycle, the clock can be entrained by light, activity, or food. Here we show that the DNA-binding activity of the Clock:BMAL1 and NPAS2:BMAL1 heterodimers is regulated by the redox state of nicotinamide adenine dinucleotide (NAD) cofactors in a purified system. The reduced forms of the redox cofactors, NAD(H) and NADP(H), strongly enhance DNA binding of the Clock:BMAL1 and NPAS2:BMAL1 heterodimers, whereas the oxidized forms inhibit. These observations raise the possibility that food, neuronal activity, or both may entrain the circadian clock by direct modulation of cellular redox state.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rutter, J -- Reick, M -- Wu, L C -- McKnight, S L -- 1RO1MH59388/MH/NIMH NIH HHS/ -- NIH5-T32-GM08-291-12/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2001 Jul 20;293(5529):510-4. Epub 2001 Jul 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Texas-Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9152, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11441146" target="_blank"〉PubMed〈/a〉
    Keywords: ARNTL Transcription Factors ; Animals ; Aryl Hydrocarbon Receptor Nuclear Translocator ; Basic Helix-Loop-Helix Transcription Factors ; Biological Clocks ; CLOCK Proteins ; Cell Line ; Circadian Rhythm ; DNA/*metabolism ; *DNA-Binding Proteins ; Dimerization ; Helix-Loop-Helix Motifs ; Humans ; L-Lactate Dehydrogenase/genetics/metabolism ; Mice ; NAD/*metabolism/pharmacology ; NADP/*metabolism/pharmacology ; Nerve Tissue Proteins/chemistry/*metabolism ; Oxidation-Reduction ; *Receptors, Aryl Hydrocarbon ; Recombinant Proteins/metabolism ; Trans-Activators/chemistry/*metabolism ; Transcription Factors/chemistry/*metabolism
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  • 93
    Publication Date: 2002-09-14
    Description: Mutations in the BRCA2 (breast cancer susceptibility gene 2) tumor suppressor lead to chromosomal instability due to defects in the repair of double-strand DNA breaks (DSBs) by homologous recombination, but BRCA2's role in this process has been unclear. Here, we present the 3.1 angstrom crystal structure of a approximately 90-kilodalton BRCA2 domain bound to DSS1, which reveals three oligonucleotide-binding (OB) folds and a helix-turn-helix (HTH) motif. We also (i) demonstrate that this BRCA2 domain binds single-stranded DNA, (ii) present its 3.5 angstrom structure bound to oligo(dT)9, (iii) provide data that implicate the HTH motif in dsDNA binding, and (iv) show that BRCA2 stimulates RAD51-mediated recombination in vitro. These findings establish that BRCA2 functions directly in homologous recombination and provide a structural and biochemical basis for understanding the loss of recombination-mediated DSB repair in BRCA2-associated cancers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Haijuan -- Jeffrey, Philip D -- Miller, Julie -- Kinnucan, Elspeth -- Sun, Yutong -- Thoma, Nicolas H -- Zheng, Ning -- Chen, Phang-Lang -- Lee, Wen-Hwa -- Pavletich, Nikola P -- New York, N.Y. -- Science. 2002 Sep 13;297(5588):1837-48.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Sloan-Kettering Division, 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/12228710" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; BRCA2 Protein/*chemistry/genetics/*metabolism ; Binding Sites ; Crystallography, X-Ray ; DNA/metabolism ; *DNA Repair ; DNA, Single-Stranded/*metabolism ; DNA-Binding Proteins/metabolism ; Genes, BRCA2 ; Helix-Turn-Helix Motifs ; Humans ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Mice ; Molecular Sequence Data ; Mutation ; Proteasome Endopeptidase Complex ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Proteins/chemistry/*metabolism ; Rad51 Recombinase ; Rats ; *Recombination, Genetic
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  • 94
    Publication Date: 2002-11-02
    Description: beta-Defensins are small antimicrobial peptides of the innate immune system produced in response to microbial infection of mucosal tissue and skin. We demonstrate that murine beta-defensin 2 (mDF2beta) acts directly on immature dendritic cells as an endogenous ligand for Toll-like receptor 4 (TLR-4), inducing up-regulation of costimulatory molecules and dendritic cell maturation. These events, in turn, trigger robust, type 1 polarized adaptive immune responses in vivo, suggesting that mDF2beta may play an important role in immunosurveillance against pathogens and, possibly, self antigens or tumor antigens.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Biragyn, Arya -- Ruffini, Pier Adelchi -- Leifer, Cynthia A -- Klyushnenkova, Elena -- Shakhov, Alexander -- Chertov, Oleg -- Shirakawa, Aiko K -- Farber, Joshua M -- Segal, David M -- Oppenheim, Joost J -- Kwak, Larry W -- N0L-CO-12400/CO/NCI NIH HHS/ -- New York, N.Y. -- Science. 2002 Nov 1;298(5595):1025-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, MD 20892, USA. arya@mail.ncifcrf.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12411706" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, Neoplasm/immunology ; Cancer Vaccines/immunology ; Cell Line ; Cytokines/biosynthesis ; Dendritic Cells/*immunology ; *Drosophila Proteins ; Female ; Humans ; Interferon-alpha/physiology ; Ligands ; Lipopolysaccharides/immunology/pharmacology ; Lymphocyte Culture Test, Mixed ; Membrane Glycoproteins/genetics/*physiology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Neoplasms/immunology/therapy ; Receptors, CCR6 ; Receptors, Cell Surface/genetics/*physiology ; Receptors, Chemokine/metabolism ; Recombinant Fusion Proteins/pharmacology ; Signal Transduction ; Toll-Like Receptor 4 ; Toll-Like Receptors ; Transfection ; beta-Defensins/pharmacology/*physiology
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  • 95
    Publication Date: 2002-05-25
    Description: The sulfated peptide phytosulfokine (PSK) is an intercellular signal that plays a key role in cellular dedifferentiation and proliferation in plants. Using ligand-based affinity chromatography, we purified a 120-kilodalton membrane protein, specifically interacting with PSK, from carrot microsomal fractions. The corresponding complementary DNA encodes a 1021-amino acid receptor kinase that contains extracellular leucine-rich repeats, a single transmembrane domain, and a cytoplasmic kinase domain. Overexpression of this receptor kinase in carrot cells caused enhanced callus growth in response to PSK and a substantial increase in the number of tritium-labeled PSK binding sites, suggesting that PSK and this receptor kinase act as a ligand-receptor pair.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Matsubayashi, Yoshikatsu -- Ogawa, Mari -- Morita, Akiko -- Sakagami, Youji -- New York, N.Y. -- Science. 2002 May 24;296(5572):1470-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate School of Bio-Agricultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan. matsu@agr.nagoya-u.ac.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12029134" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Binding, Competitive ; Cell Line ; Chromatography, Affinity ; DNA, Complementary ; Daucus carota/cytology/*enzymology/genetics/growth & development ; Genes, Plant ; Glycosylation ; Leucine ; Ligands ; Microsomes/enzymology ; Molecular Sequence Data ; Molecular Weight ; Peptide Hormones ; *Plant Growth Regulators ; Plant Proteins/*chemistry/genetics/isolation & purification/*metabolism ; Plants, Genetically Modified ; Polymerase Chain Reaction ; Protein Structure, Tertiary ; Receptors, Cell Surface/*chemistry/genetics/isolation & purification/*metabolism ; Repetitive Sequences, Amino Acid
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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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  • 96
    Publication Date: 2002-02-02
    Description: The Golgi apparatus is partitioned during mitosis in animal cells by a process of fragmentation, dispersal, and reassembly in each daughter cell. We fractionated the Golgi apparatus in vivo using the drug brefeldin A or a dominant-negative mutant of the Sar1p protein. After these treatments, Golgi enzymes moved back to the endoplasmic reticulum, leaving behind a matrix of Golgi structural proteins. Under these conditions, cells still entered and exited mitosis normally, and their Golgi matrix partitioned in a manner very similar to that of the complete organelle. Thus, the matrix may be the partitioning unit of the Golgi apparatus and may carry the Golgi enzyme-containing membranes into the daughter cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Seemann, Joachim -- Pypaert, Marc -- Taguchi, Tomohiko -- Malsam, Jorg -- Warren, Graham -- New York, N.Y. -- Science. 2002 Feb 1;295(5556):848-51.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, Ludwig Institute for Cancer Research, Yale University School of Medicine, 333 Cedar Street, Post Office Box 208002, New Haven, CT 06520-8002, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11823640" target="_blank"〉PubMed〈/a〉
    Keywords: Anaphase ; Animals ; Autoantigens ; Brefeldin A/pharmacology ; Cell Line ; Endoplasmic Reticulum/enzymology ; Golgi Apparatus/*metabolism/ultrastructure ; HeLa Cells ; Humans ; Interphase ; Intracellular Membranes/metabolism/ultrastructure ; Mannosidases/metabolism ; Membrane Proteins/metabolism ; Metaphase ; Microscopy, Electron ; Microscopy, Fluorescence ; *Mitosis ; Monomeric GTP-Binding Proteins/pharmacology ; N-Acetylglucosaminyltransferases/metabolism ; Protein Disulfide-Isomerases/metabolism ; Rats ; *Saccharomyces cerevisiae Proteins ; Telophase ; Vesicular Transport Proteins
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 97
    Publication Date: 2002-04-20
    Description: For half a century, successful antifolate therapy against Plasmodium falciparum malaria has been attributed to host-parasite differences in drug binding to dihydrofolate reductase-thymidylate synthase (DHFR-TS). Selectivity may also arise through previously unappreciated differences in regulation of this drug target. The DHFR-TS of Plasmodium binds its cognate messenger RNA (mRNA) and inhibits its own translation. However, unlike translational regulation of DHFR or TS in humans, DHFR-TS mRNA binding is not coupled to enzyme active sites. Thus, antifolate treatment does not relieve translational inhibition and parasites cannot replenish dead enzyme.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3830934/" 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/PMC3830934/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Kai -- Rathod, Pradipsinh K -- AI26912/AI/NIAID NIH HHS/ -- AI40956/AI/NIAID NIH HHS/ -- R01 AI026912/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2002 Apr 19;296(5567):545-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, The Catholic University of America, Washington, DC 20064, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11964483" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antimalarials/pharmacology ; Catalytic Domain ; Cell Line ; Folic Acid Antagonists/*pharmacology ; Host-Parasite Interactions ; Humans ; Multienzyme Complexes/chemistry/*genetics/*metabolism ; Plasmodium falciparum/*enzymology/genetics ; Protein Biosynthesis ; RNA, Messenger/genetics/metabolism ; RNA, Protozoan/genetics/metabolism ; Recombinant Proteins/genetics/metabolism ; Tetrahydrofolate Dehydrogenase/chemistry/*genetics/*metabolism ; Thymidylate Synthase/chemistry/*genetics/*metabolism ; Triazines/pharmacology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 98
    Publication Date: 2002-09-28
    Description: It has been known since 1986 that CD8 T lymphocytes from certain HIV-1-infected individuals who are immunologically stable secrete a soluble factor, termed CAF, that suppresses HIV-1 replication. However, the identity of CAF remained elusive despite an extensive search. By means of a protein-chip technology, we identified a cluster of proteins that were secreted when CD8 T cells from long-term nonprogressors with HIV-1 infection were stimulated. These proteins were identified as alpha-defensin 1, 2, and 3 on the basis of specific antibody recognition and amino acid sequencing. CAF activity was eliminated or neutralized by an antibody specific for human alpha-defensins. Synthetic and purified preparations of alpha-defensins also inhibited the replication of HIV-1 isolates in vitro. Taken together, our results indicate that alpha-defensin 1, 2, and 3 collectively account for much of the anti-HIV-1 activity of CAF that is not attributable to beta-chemokines.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Linqi -- Yu, Wenjie -- He, Tian -- Yu, Jian -- Caffrey, Rebecca E -- Dalmasso, Enrique A -- Fu, Siyu -- Pham, Thang -- Mei, Jianfeng -- Ho, Jaclyn J -- Zhang, Wenyong -- Lopez, Peter -- Ho, David D -- AI-42848/AI/NIAID NIH HHS/ -- M01-RR00102/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2002 Nov 1;298(5595):995-1000. Epub 2002 Sep 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA. lzhang@adarc.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12351674" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Antibodies, Monoclonal ; Antiviral Agents/chemistry/isolation & purification/*pharmacology ; CD8-Positive T-Lymphocytes/chemistry/*immunology ; Cells, Cultured ; Chemokines, CC/immunology/physiology ; HIV Infections/*immunology/virology ; HIV Long-Term Survivors ; HIV-1/drug effects/*physiology ; Humans ; Mass Spectrometry ; Molecular Sequence Data ; Neutrophils/chemistry/immunology ; Protein Array Analysis ; Virus Replication ; alpha-Defensins/chemistry/isolation & purification/pharmacology/*physiology
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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: 2002-02-16
    Description: The corepressor CtBP (carboxyl-terminal binding protein) is involved in transcriptional pathways important for development, cell cycle regulation, and transformation. We demonstrate that CtBP binding to cellular and viral transcriptional repressors is regulated by the nicotinamide adenine dinucleotides NAD+ and NADH, with NADH being two to three orders of magnitude more effective. Levels of free nuclear nicotinamide adenine dinucleotides, determined using two-photon microscopy, correspond to the levels required for half-maximal CtBP binding and are considerably lower than those previously reported. Agents capable of increasing NADH levels stimulate CtBP binding to its partners in vivo and potentiate CtBP-mediated repression. We propose that this ability to detect changes in nuclear NAD+/NADH ratio allows CtBP to serve as a redox sensor for transcription.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Qinghong -- Piston, David W -- Goodman, Richard H -- K01 CA096561/CA/NCI NIH HHS/ -- R01 CA115468/CA/NCI NIH HHS/ -- R01 CA115468-05/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2002 Mar 8;295(5561):1895-7. Epub 2002 Feb 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vollum Institute, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97201, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11847309" target="_blank"〉PubMed〈/a〉
    Keywords: Adenovirus E1A Proteins/metabolism ; Alcohol Oxidoreductases ; Amino Acid Sequence ; Animals ; Binding Sites ; Cadherins/genetics ; Cell Nucleus/*metabolism ; Cytoplasm/metabolism ; DNA-Binding Proteins/chemistry/genetics/*metabolism ; *Gene Expression Regulation ; HeLa Cells ; Homeodomain Proteins/metabolism ; Humans ; Microscopy, Fluorescence ; Molecular Sequence Data ; Mutation ; NAD/*metabolism ; Oxidation-Reduction ; Phosphoproteins/chemistry/genetics/*metabolism ; Promoter Regions, Genetic ; Protein Binding ; Recombinant Fusion Proteins/metabolism ; Repressor Proteins/*metabolism ; *Transcription Factors ; Transcription, Genetic ; Transfection
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 100
    Publication Date: 2002-05-23
    Description: Mechanical and thermal cues stimulate a specialized group of sensory neurons that terminate in the skin. Three members of the transient receptor potential (TRP) family of channels are expressed in subsets of these neurons and are activated at distinct physiological temperatures. Here, we describe the cloning and characterization of a novel thermosensitive TRP channel. TRPV3 has a unique threshold: It is activated at innocuous (warm) temperatures and shows an increased response at noxious temperatures. TRPV3 is specifically expressed in keratinocytes; hence, skin cells are capable of detecting heat via molecules similar to those in heat-sensing neurons.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Peier, Andrea M -- Reeve, Alison J -- Andersson, David A -- Moqrich, Aziz -- Earley, Taryn J -- Hergarden, Anne C -- Story, Gina M -- Colley, Sian -- Hogenesch, John B -- McIntyre, Peter -- Bevan, Stuart -- Patapoutian, Ardem -- New York, N.Y. -- Science. 2002 Jun 14;296(5575):2046-9. Epub 2002 May 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12016205" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Animals, Newborn ; Blotting, Northern ; CHO Cells ; Capsaicin/*analogs & derivatives/pharmacology ; *Cation Transport Proteins ; Cell Line ; Cells, Cultured ; Cloning, Molecular ; Cricetinae ; Epidermis/cytology/innervation/metabolism ; Ganglia, Spinal/metabolism ; *Hot Temperature ; Humans ; In Situ Hybridization ; Ion Channels/chemistry/genetics/*metabolism ; Keratinocytes/*metabolism ; Membrane Potentials ; Mice ; Molecular Sequence Data ; Nerve Endings/physiology ; Neurons/physiology ; Patch-Clamp Techniques ; RNA, Messenger/genetics/metabolism ; Ruthenium Red/pharmacology ; Signal Transduction ; Spinal Cord/metabolism ; TRPV Cation Channels ; Temperature
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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