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  • Cell Line  (80)
  • American Association for the Advancement of Science (AAAS)  (80)
  • American Meteorological Society
  • 2000-2004  (80)
  • 1995-1999
  • 2001  (80)
Collection
Publisher
  • American Association for the Advancement of Science (AAAS)  (80)
  • American Meteorological Society
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  • 2000-2004  (80)
  • 1995-1999
Year
  • 1
    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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    Electronic ISSN: 1095-9203
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  • 2
    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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  • 3
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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
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    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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  • 5
    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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  • 6
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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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  • 7
    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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  • 8
    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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  • 9
    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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  • 10
    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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  • 11
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    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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  • 12
    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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  • 13
    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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  • 14
    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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  • 15
    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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  • 16
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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〉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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  • 17
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    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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  • 18
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    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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  • 19
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    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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  • 20
    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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  • 21
    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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  • 22
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    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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  • 23
    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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  • 24
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    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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  • 25
    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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  • 26
    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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  • 27
    Publication Date: 2001-04-09
    Description: HIF (hypoxia-inducible factor) is a transcription factor that plays a pivotal role in cellular adaptation to changes in oxygen availability. In the presence of oxygen, HIF is targeted for destruction by an E3 ubiquitin ligase containing the von Hippel-Lindau tumor suppressor protein (pVHL). We found that human pVHL binds to a short HIF-derived peptide when a conserved proline residue at the core of this peptide is hydroxylated. Because proline hydroxylation requires molecular oxygen and Fe(2+), this protein modification may play a key role in mammalian oxygen sensing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ivan, M -- Kondo, K -- Yang, H -- Kim, W -- Valiando, J -- Ohh, M -- Salic, A -- Asara, J M -- Lane, W S -- Kaelin , W G Jr -- New York, N.Y. -- Science. 2001 Apr 20;292(5516):464-8. Epub 2001 Apr 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Dana-Farber Cancer Institute and Brigham and Women's Hospital, Howard Hughes Medical Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11292862" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Basic Helix-Loop-Helix Transcription Factors ; Cell Hypoxia ; Cell Line ; Cobalt/pharmacology ; Deferoxamine/pharmacology ; Humans ; Hydroxylation ; Hydroxyproline/*metabolism ; *Ligases ; Mass Spectrometry ; Mice ; Molecular Sequence Data ; Oxygen/*physiology ; Protein Structure, Tertiary ; Proteins/*metabolism ; Recombinant Fusion Proteins/metabolism ; Trans-Activators/chemistry/genetics/*metabolism ; Transcription Factors/*metabolism ; Tumor Cells, Cultured ; *Tumor Suppressor Proteins ; *Ubiquitin-Protein Ligases ; Ubiquitins/metabolism ; Von Hippel-Lindau Tumor Suppressor Protein
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  • 28
    Publication Date: 2001-10-27
    Description: In Caenorhabditis elegans, lin-4 and let-7 encode 22- and 21-nucleotide (nt) RNAs, respectively, which function as key regulators of developmental timing. Because the appearance of these short RNAs is regulated during development, they are also referred to as small temporal RNAs (stRNAs). We show that many 21- and 22-nt expressed RNAs, termed microRNAs, exist in invertebrates and vertebrates and that some of these novel RNAs, similar to let-7 stRNA, are highly conserved. This suggests that sequence-specific, posttranscriptional regulatory mechanisms mediated by small RNAs are more general than previously appreciated.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lagos-Quintana, M -- Rauhut, R -- Lendeckel, W -- Tuschl, T -- New York, N.Y. -- Science. 2001 Oct 26;294(5543):853-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular Biochemistry, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, D-37077 Gottingen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11679670" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Pairing ; Blotting, Northern ; Cell Line ; Cloning, Molecular ; Computational Biology ; Conserved Sequence ; Drosophila melanogaster/embryology/genetics ; Evolution, Molecular ; Gene Expression Profiling ; *Gene Expression Regulation ; Gene Expression Regulation, Developmental ; HeLa Cells ; Humans ; Multigene Family ; Nucleic Acid Conformation ; Organ Specificity ; RNA/*chemistry/*genetics/metabolism ; RNA Precursors/chemistry/genetics/metabolism ; RNA, Untranslated/*chemistry/*genetics/metabolism
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  • 29
    Publication Date: 2001-08-04
    Description: Many hematopoietic cells undergo apoptosis when deprived of specific cytokines, and this process requires de novo RNA/protein synthesis. Using DNA microarrays to analyze interleukin-3 (IL-3)-dependent murine FL5.12 pro-B cells, we found that the gene undergoing maximal transcriptional induction after cytokine withdrawal is 24p3, which encodes a secreted lipocalin. Conditioned medium from IL-3-deprived FL5.12 cells contained 24p3 and induced apoptosis in naive FL5.12 cells even when IL-3 was present. 24p3 also induced apoptosis in a wide variety of leukocytes but not other cell types. Apoptotic sensitivity correlated with the presence of a putative 24p3 cell surface receptor. We conclude that IL-3 deprivation activates 24p3 transcription, leading to synthesis and secretion of 24p3, which induces apoptosis through an autocrine pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Devireddy, L R -- Teodoro, J G -- Richard, F A -- Green, M R -- New York, N.Y. -- Science. 2001 Aug 3;293(5531):829-34.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Program in Gene Function and Expression and Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11486081" target="_blank"〉PubMed〈/a〉
    Keywords: Acute-Phase Proteins/*genetics/*metabolism ; Animals ; *Apoptosis/drug effects ; Autocrine Communication ; Carrier Proteins/metabolism ; Cell Line ; Cells, Cultured ; Culture Media, Conditioned ; Dexamethasone/pharmacology ; *Gene Expression Regulation ; Humans ; Insulin-Like Growth Factor I/pharmacology ; Interleukin-3/*metabolism ; Interleukins/metabolism ; Leukocytes/cytology/*physiology ; Lipocalins ; Mice ; Oligonucleotide Array Sequence Analysis ; Oncogene Proteins/*genetics/*metabolism ; Phosphorylation ; Proto-Oncogene Proteins ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Receptors, Cell Surface/metabolism ; Recombinant Fusion Proteins/metabolism ; Transcription, Genetic ; Tumor Cells, Cultured ; bcl-Associated Death Protein ; bcl-X Protein
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  • 30
    Publication Date: 2001-12-01
    Description: Neurotrophins are growth factors that promote cell survival, differentiation, and cell death. They are synthesized as proforms that can be cleaved intracellularly to release mature, secreted ligands. Although proneurotrophins have been considered inactive precursors, we show here that the proforms of nerve growth factor (NGF) and the proforms of brain derived neurotrophic factor (BDNF) are secreted and cleaved extracellularly by the serine protease plasmin and by selective matrix metalloproteinases (MMPs). ProNGF is a high-affinity ligand for p75(NTR) with high affinity and induced p75NTR-dependent apoptosis in cultured neurons with minimal activation of TrkA-mediated differentiation or survival. The biological action of neurotrophins is thus regulated by proteolytic cleavage, with proforms preferentially activating p75NTR to mediate apoptosis and mature forms activating Trk receptors to promote survival.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, R -- Kermani, P -- Teng, K K -- Hempstead, B L -- NS30687/NS/NINDS NIH HHS/ -- T32 EY07138/EY/NEI NIH HHS/ -- New York, N.Y. -- Science. 2001 Nov 30;294(5548):1945-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Hematology, Department of Medicine, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11729324" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis/drug effects ; Brain-Derived Neurotrophic Factor/chemistry/metabolism/pharmacology/secretion ; Cell Death/drug effects ; Cell Differentiation/drug effects ; Cell Line ; *Cell Survival/drug effects ; Fibrinolysin/metabolism ; Furin ; Humans ; Inhibitory Concentration 50 ; Matrix Metalloproteinases/metabolism ; Mice ; Nerve Growth Factor/chemistry/metabolism/pharmacology/secretion ; Nerve Growth Factors/chemistry/*metabolism/pharmacology/*secretion ; Neurons/cytology/drug effects ; Phosphorylation/drug effects ; Protein Precursors/chemistry/*metabolism/pharmacology/*secretion ; Protein Processing, Post-Translational ; Rats ; Receptor, Nerve Growth Factor ; Receptor, trkA/metabolism ; Receptors, Nerve Growth Factor/metabolism ; Subtilisins/metabolism
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  • 31
    Publication Date: 2001-10-06
    Description: Although trafficking and degradation of several membrane proteins are regulated by ubiquitination catalyzed by E3 ubiquitin ligases, there has been little evidence connecting ubiquitination with regulation of mammalian G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor (GPCR) function. Agonist stimulation of endogenous or transfected beta2-adrenergic receptors (beta2ARs) led to rapid ubiquitination of both the receptors and the receptor regulatory protein, beta-arrestin. Moreover, proteasome inhibitors reduced receptor internalization and degradation, thus implicating a role for the ubiquitination machinery in the trafficking of the beta2AR. Receptor ubiquitination required beta-arrestin, which bound to the E3 ubiquitin ligase Mdm2. Abrogation of beta-arrestin ubiquitination, either by expression in Mdm2-null cells or by dominant-negative forms of Mdm2 lacking E3 ligase activity, inhibited receptor internalization with marginal effects on receptor degradation. However, a beta2AR mutant lacking lysine residues, which was not ubiquitinated, was internalized normally but was degraded ineffectively. These findings delineate an adapter role of beta-arrestin in mediating the ubiquitination of the beta2AR and indicate that ubiquitination of the receptor and of beta-arrestin have distinct and obligatory roles in the trafficking and degradation of this prototypic GPCR.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shenoy, S K -- McDonald, P H -- Kohout, T A -- Lefkowitz, R J -- HL16037/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2001 Nov 9;294(5545):1307-13. Epub 2001 Oct 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Medicine, Duke University Medical Center, Box 3821, Durham, NC 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11588219" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arrestins/*metabolism ; COS Cells ; Catalysis ; Cell Line ; Cricetinae ; Cricetulus ; Cysteine Endopeptidases/metabolism ; Humans ; Isoproterenol/pharmacology ; Ligases/metabolism ; Multienzyme Complexes/antagonists & inhibitors/metabolism ; Mutation ; *Nuclear Proteins ; Phosphorylation ; Proteasome Endopeptidase Complex ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins c-mdm2 ; Receptors, Adrenergic, beta-2/genetics/*metabolism ; Recombinant Proteins/metabolism ; Transfection ; Ubiquitin/*metabolism ; Ubiquitin-Protein Ligases
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  • 32
    Publication Date: 2001-01-06
    Description: Intracellular bacteria and parasites typically invade host cells through the formation of an internalization vacuole around the invading pathogen. Plasmodium sporozoites, the infective stage of the malaria parasite transmitted by mosquitoes, have an alternative mechanism to enter cells. We observed breaching of the plasma membrane of the host cell followed by rapid repair. This mode of entry did not result in the formation of a vacuole around the sporozoite, and was followed by exit of the parasite from the host cell. Sporozoites traversed the cytosol of several cells before invading a hepatocyte by formation of a parasitophorous vacuole, in which they developed into the next infective stage. Sporozoite migration through several cells in the mammalian host appears to be essential for the completion of the life cycle.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mota, M M -- Pradel, G -- Vanderberg, J P -- Hafalla, J C -- Frevert, U -- Nussenzweig, R S -- Nussenzweig, V -- Rodriguez, A -- New York, N.Y. -- Science. 2001 Jan 5;291(5501):141-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, New York University School of Medicine, 341 East 25 Street, New York, NY 10010, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11141568" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cell Membrane/parasitology/physiology/ultrastructure ; Cell Movement ; Cytosol/metabolism/parasitology ; Dextrans/metabolism ; Endocytosis ; Flow Cytometry ; Fluorescein-5-isothiocyanate/*analogs & derivatives/metabolism ; Hepatocytes/*parasitology/ultrastructure ; Malaria/parasitology ; Mice ; Mice, Inbred BALB C ; Plasmodium/physiology ; Plasmodium yoelii/growth & development/*physiology ; Propidium/metabolism ; Toxoplasma/physiology ; Tumor Cells, Cultured ; Vacuoles/parasitology/ultrastructure
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  • 33
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-03-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Murray, A W -- New York, N.Y. -- Science. 2001 Feb 23;291(5508):1499-502.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA. amurray@mcb.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11234079" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Evolution ; Cell Cycle ; *Cell Division ; Cell Line ; Cells, Cultured ; Centrioles/*physiology ; Centrosome/*physiology ; Chromosome Segregation ; DNA Replication ; Microtubules/physiology ; Mitosis ; Proteins/physiology ; Saccharomycetales/cytology/physiology ; Spindle Apparatus/physiology
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  • 34
    Publication Date: 2001-02-24
    Description: Little is known about the identity of endoplasmic reticulum (ER) export signals and how they are used to regulate the number of proteins on the cell surface. Here, we describe two ER export signals that profoundly altered the steady-state distribution of potassium channels and were required for channel localization to the plasma membrane. When transferred to other potassium channels or a G protein-coupled receptor, these ER export signals increased the number of functional proteins on the cell surface. Thus, ER export of membrane proteins is not necessarily limited by folding or assembly, but may be under the control of specific export signals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ma, D -- Zerangue, N -- Lin, Y F -- Collins, A -- Yu, M -- Jan, Y N -- Jan, L Y -- New York, N.Y. -- Science. 2001 Jan 12;291(5502):316-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143-0725, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11209084" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Amino Acid Motifs ; Amino Acid Sequence ; Amino Acid Substitution ; Animals ; COS Cells ; Cell Line ; Cell Membrane/*metabolism ; Endoplasmic Reticulum/*metabolism ; G Protein-Coupled Inwardly-Rectifying Potassium Channels ; Glycosylation ; Golgi Apparatus/metabolism ; Kv1.2 Potassium Channel ; Mice ; Molecular Sequence Data ; Oocytes ; Potassium Channels/*chemistry/genetics/*metabolism ; *Potassium Channels, Inwardly Rectifying ; *Potassium Channels, Voltage-Gated ; Protein Folding ; *Protein Sorting Signals ; Protein Transport ; Receptors, GABA-B/chemistry/metabolism ; Receptors, Retinoic Acid/chemistry/metabolism ; Recombinant Fusion Proteins/chemistry/metabolism ; Retinoid X Receptors ; Transcription Factors/chemistry/metabolism ; Xenopus
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  • 35
    Publication Date: 2001-03-07
    Description: EDG-1 is a heterotrimeric guanine nucleotide binding protein-coupled receptor (GPCR) for sphingosine-1-phosphate (SPP). Cell migration toward platelet-derived growth factor (PDGF), which stimulates sphingosine kinase and increases intracellular SPP, was dependent on expression of EDG-1. Deletion of edg-1 or inhibition of sphingosine kinase suppressed chemotaxis toward PDGF and also activation of the small guanosine triphosphatase Rac, which is essential for protrusion of lamellipodia and forward movement. Moreover, PDGF activated EDG-1, as measured by translocation of beta-arrestin and phosphorylation of EDG-1. Our results reveal a role for receptor cross-communication in which activation of a GPCR by a receptor tyrosine kinase is critical for cell motility.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hobson, J P -- Rosenfeldt, H M -- Barak, L S -- Olivera, A -- Poulton, S -- Caron, M G -- Milstien, S -- Spiegel, S -- CA61774/CA/NCI NIH HHS/ -- GM43880/GM/NIGMS NIH HHS/ -- HL-61365/HL/NHLBI NIH HHS/ -- NS19576/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2001 Mar 2;291(5509):1800-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Georgetown University Medical Center, Washington, DC 20007, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11230698" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arrestins/metabolism ; Cell Line ; Cell Membrane/metabolism ; Cells, Cultured ; *Chemotaxis/drug effects ; Gene Deletion ; Humans ; Immediate-Early Proteins/genetics/*metabolism ; *Lysophospholipids ; Mice ; Muscle, Smooth, Vascular/cytology/metabolism ; Phosphorylation ; Phosphotransferases (Alcohol Group Acceptor)/antagonists & inhibitors/metabolism ; Platelet-Derived Growth Factor/metabolism/*pharmacology ; Proto-Oncogene Proteins c-sis ; Receptor Cross-Talk ; *Receptors, Cell Surface ; *Receptors, G-Protein-Coupled ; Receptors, Lysophospholipid ; Receptors, Platelet-Derived Growth Factor/metabolism ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; Sphingosine/*analogs & derivatives/*metabolism/pharmacology ; Transfection
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  • 36
    Publication Date: 2001-09-08
    Description: Nonsense-mediated messenger RNA (mRNA) decay, or NMD, is a critical process of selective degradation of mRNAs that contain premature stop codons. NMD depends on both pre-mRNA splicing and translation, and it requires recognition of the position of stop codons relative to exon-exon junctions. A key factor in NMD is hUpf3, a mostly nuclear protein that shuttles between the nucleus and cytoplasm and interacts specifically with spliced mRNAs. We found that hUpf3 interacts with Y14, a component of post-splicing mRNA-protein (mRNP) complexes, and that hUpf3 is enriched in Y14-containing mRNP complexes. The mRNA export factors Aly/REF and TAP are also associated with nuclear hUpf3, indicating that hUpf3 is in mRNP complexes that are poised for nuclear export. Like Y14 and Aly/REF, hUpf3 binds to spliced mRNAs specifically ( approximately 20 nucleotides) upstream of exon-exon junctions. The splicing-dependent binding of hUpf3 to mRNAs before export, as part of the complex that assembles near exon-exon junctions, allows it to serve as a link between splicing and NMD in the cytoplasm.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, V N -- Kataoka, N -- Dreyfuss, G -- 5 R01 GM37125.14/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2001 Sep 7;293(5536):1832-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11546873" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions/genetics/metabolism ; Active Transport, Cell Nucleus ; Cell Line ; Codon, Nonsense/*genetics ; DNA-Binding Proteins/genetics/metabolism ; Exons/*genetics ; Fungal Proteins/genetics/*metabolism ; Globins/genetics ; Humans ; Macromolecular Substances ; Models, Biological ; Precipitin Tests ; Protein Binding ; RNA Splicing/*genetics ; RNA, Messenger/genetics/metabolism ; RNA-Binding Proteins/genetics/*metabolism ; Recombinant Fusion Proteins/genetics/metabolism ; Ribonucleoproteins/chemistry/metabolism ; *Saccharomyces cerevisiae Proteins ; Substrate Specificity
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  • 37
    Publication Date: 2001-03-10
    Description: Netrins stimulate and orient axon growth through a mechanism requiring receptors of the DCC family. It has been unclear, however, whether DCC proteins are involved directly in signaling or are mere accessory proteins in a receptor complex. Further, although netrins bind cells expressing DCC, direct binding to DCC has not been demonstrated. Here we show that netrin-1 binds DCC and that the DCC cytoplasmic domain fused to a heterologous receptor ectodomain can mediate guidance through a mechanism involving derepression of cytoplasmic domain multimerization. Activation of the adenosine A2B receptor, proposed to contribute to netrin effects on axons, is not required for rat commissural axon outgrowth or Xenopus spinal axon attraction to netrin-1. Thus, DCC plays a central role in netrin signaling of axon growth and guidance independent of A2B receptor activation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stein, E -- Zou, Y -- Poo , M -- Tessier-Lavigne, M -- New York, N.Y. -- Science. 2001 Mar 9;291(5510):1976-82.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Anatomy, Howard Hughes Medical Institute, University of California, San Francisco, CA 94143-0452, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11239160" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/*physiology ; Cell Adhesion Molecules/chemistry/genetics/*metabolism ; Cell Line ; Cell Movement ; Cells, Cultured ; Culture Techniques ; Embryo, Nonmammalian ; Growth Cones/physiology ; Hepatocyte Growth Factor/metabolism/pharmacology ; Ligands ; Nerve Growth Factors/*metabolism/pharmacology ; Neurons/metabolism ; Protein Conformation ; Protein Structure, Tertiary ; Purinergic P1 Receptor Agonists ; Purinergic P1 Receptor Antagonists ; Rats ; Receptor, Adenosine A2B ; Receptors, Cell Surface/chemistry/genetics/*metabolism ; Receptors, Purinergic P1/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; Spinal Cord/cytology/metabolism ; *Tumor Suppressor Proteins ; Xanthines/pharmacology ; Xenopus/embryology
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  • 38
    Publication Date: 2001-08-18
    Description: We characterized an activation mechanism of the human LTRPC2 protein, a member of the transient receptor potential family of ion channels, and demonstrated that LTRPC2 mediates Ca2+ influx into immunocytes. Intracellular pyrimidine nucleotides, adenosine 5'-diphosphoribose (ADPR), and nicotinamide adenine dinucleotide (NAD), directly activated LTRPC2, which functioned as a Ca2+-permeable nonselective cation channel and enabled Ca2+ influx into cells. This activation was suppressed by intracellular adenosine triphosphate. These results reveal that ADPR and NAD act as intracellular messengers and may have an important role in Ca2+ influx by activating LTRPC2 in immunocytes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sano, Y -- Inamura, K -- Miyake, A -- Mochizuki, S -- Yokoi, H -- Matsushime, H -- Furuichi, K -- New York, N.Y. -- Science. 2001 Aug 17;293(5533):1327-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Medicine Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. sano.yorikata@yamanouchi.co.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11509734" target="_blank"〉PubMed〈/a〉
    Keywords: ADP-ribosyl Cyclase ; Adenosine Diphosphate Ribose/metabolism/pharmacology ; Adenosine Triphosphate/metabolism/pharmacology ; *Antigens, CD ; Antigens, CD38 ; Antigens, Differentiation/metabolism ; Apoptosis ; Calcium/*metabolism ; Calcium Channels/*metabolism ; Cell Line ; Eosinophils/*metabolism ; Humans ; *Ion Channels ; Jurkat Cells ; Membrane Glycoproteins ; Membrane Potentials ; *Membrane Proteins ; Monocytes/*metabolism ; NAD/metabolism/pharmacology ; NAD+ Nucleosidase/metabolism ; Patch-Clamp Techniques ; Reverse Transcriptase Polymerase Chain Reaction ; T-Lymphocytes/*metabolism ; TRPM Cation Channels
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  • 39
    Publication Date: 2001-11-10
    Description: Processing of proteins for major histocompatibility complex (MHC) class II-restricted presentation to CD4-positive T lymphocytes occurs after they are internalized by antigen-presenting cells (APCs). Antigenic proteins frequently contain disulfide bonds, and their reduction in the endocytic pathway facilitates processing. In humans, a gamma interferon-inducible lysosomal thiol reductase (GILT) is constitutively present in late endocytic compartments of APCs. Here, we identified the mouse homolog of GILT and generated a GILT knockout mouse. GILT facilitated the processing and presentation to antigen-specific T cells of protein antigens containing disulfide bonds. The response to hen egg lysozyme, a model antigen with a compact structure containing four disulfide bonds, was examined in detail.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maric, M -- Arunachalam, B -- Phan, U T -- Dong, C -- Garrett, W S -- Cannon, K S -- Alfonso, C -- Karlsson, L -- Flavell, R A -- Cresswell, P -- AI23081/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2001 Nov 9;294(5545):1361-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11701933" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; *Antigen Presentation ; Antigen-Presenting Cells/enzymology/*immunology ; Antigens/chemistry/immunology/metabolism ; Cell Line ; Dendritic Cells/enzymology ; Disulfides/chemistry ; Epitopes/immunology/metabolism ; Histocompatibility Antigens Class II/immunology/metabolism ; Hybridomas ; Hydrogen-Ion Concentration ; Immunization ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Molecular Sequence Data ; Muramidase/chemistry/*immunology/metabolism ; Oxidoreductases/chemistry/genetics/*metabolism ; Protein Conformation ; Protein Folding ; Spleen/immunology ; T-Lymphocytes/*immunology
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  • 40
    Publication Date: 2001-09-22
    Description: The localization of gammadelta T cells within epithelia suggests that these cells may contribute to the down-regulation of epithelial malignancies. We report that mice lacking gammadelta cells are highly susceptible to multiple regimens of cutaneous carcinogenesis. After exposure to carcinogens, skin cells expressed Rae-1 and H60, major histocompatibility complex-related molecules structurally resembling human MICA. Each of these is a ligand for NKG2d, a receptor expressed by cytolytic T cells and natural killer (NK) cells. In vitro, skin-associated NKG2d+ gammadelta cells killed skin carcinoma cells by a mechanism that was sensitive to blocking NKG2d engagement. Thus, local T cells may use evolutionarily conserved proteins to negatively regulate malignancy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Girardi, M -- Oppenheim, D E -- Steele, C R -- Lewis, J M -- Glusac, E -- Filler, R -- Hobby, P -- Sutton, B -- Tigelaar, R E -- Hayday, A C -- AI 27855/AI/NIAID NIH HHS/ -- KO8/PHS HHS/ -- New York, N.Y. -- Science. 2001 Oct 19;294(5542):605-9. Epub 2001 Sep 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Dermatology and Yale Skin Diseases Research Core Center, King's College, London SE1 9RT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11567106" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Carcinogens ; Cell Line ; Cytotoxicity, Immunologic ; Dimerization ; Epidermis/*immunology ; Epithelial Cells/immunology ; Histocompatibility Antigens Class I/chemistry/immunology ; Humans ; *Immunologic Surveillance ; Ligands ; Membrane Proteins/chemistry/genetics/*immunology/metabolism ; Mice ; Mice, Inbred C57BL ; Minor Histocompatibility Antigens/genetics/immunology/metabolism ; Molecular Sequence Data ; NK Cell Lectin-Like Receptor Subfamily K ; Protein Conformation ; Protein Folding ; Receptors, Antigen, T-Cell, alpha-beta/immunology ; Receptors, Antigen, T-Cell, gamma-delta/*immunology ; Receptors, Immunologic/*immunology/metabolism ; Receptors, Natural Killer Cell ; Recombinant Fusion Proteins/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Skin Neoplasms/chemically induced/*immunology ; T-Lymphocyte Subsets/*immunology
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  • 41
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-02-24
    Description: Many fungal pathogens are opportunistic, that is, they infect individuals who have a compromised immune system. Histoplasma capsulatum is a common pathogenic fungus that lives happily inside the phagosomes of macrophages. As Klein explains in his Perspective, an important H. capsulatum virulence factor, CBP1, has been found, which mops up free calcium ions within the phagosome, enabling the yeast to live under calcium-poor conditions (Sebhgati et al.). Chelating calcium ions may also have the added benefit that when the phagosome fuses with the lysosome, destructive lysosomal enzymes that require calcium ions for activity remain inactive.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Klein, B S -- New York, N.Y. -- Science. 2000 Nov 17;290(5495):1311-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatrics, University of Wisconsin-Madison, Madison, WI 53792, USA. bsklein@facstaff.wisc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11185407" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/*metabolism ; Calcium-Binding Proteins/*genetics/*metabolism ; Cell Line ; Gene Targeting ; Genes, Fungal ; Histoplasma/genetics/growth & development/metabolism/*pathogenicity ; Histoplasmosis/microbiology ; Hydrogen-Ion Concentration ; Lung Diseases, Fungal/microbiology ; Macrophages/*microbiology ; Mice ; Mutagenesis ; Phagosomes/metabolism/microbiology ; Plasmids ; Recombination, Genetic ; Temperature ; Transformation, Genetic ; Virulence
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  • 42
    Publication Date: 2001-11-27
    Description: The checkpoint kinases ATM (ataxia telangiectasia mutated) and ATR (ATM and Rad3 related) transduce genomic stress signals to halt cell cycle progression and promote DNA repair. We report the identification of an ATR-interacting protein (ATRIP) that is phosphorylated by ATR, regulates ATR expression, and is an essential component of the DNA damage checkpoint pathway. ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication. Deletion of ATR mediated by the Cre recombinase caused the loss of ATR and ATRIP expression, loss of DNA damage checkpoint responses, and cell death. Therefore, ATR is essential for the viability of human somatic cells. Small interfering RNA directed against ATRIP caused the loss of both ATRIP and ATR expression and the loss of checkpoint responses to DNA damage. Thus, ATRIP and ATR are mutually dependent partners in cell cycle checkpoint signaling pathways.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cortez, D -- Guntuku, S -- Qin, J -- Elledge, S J -- New York, N.Y. -- Science. 2001 Nov 23;294(5547):1713-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Verna and Mars McLean Department of Biochemistry and Molecular Biology, Howard Hughes Medical Institute, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11721054" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing ; Amino Acid Sequence ; Animals ; Ataxia Telangiectasia Mutated Proteins ; *Cell Cycle ; *Cell Cycle Proteins ; Cell Death ; Cell Line ; Cell Survival ; Conserved Sequence ; DNA Damage ; DNA-Binding Proteins ; *Exodeoxyribonucleases ; Exons/genetics ; Gene Deletion ; Genes, Essential/genetics ; HeLa Cells ; Humans ; Integrases/genetics/metabolism ; Molecular Sequence Data ; Molecular Weight ; Phosphoproteins/genetics/*metabolism ; Phosphorylation ; Precipitin Tests ; Protein Binding ; Protein-Serine-Threonine Kinases/genetics/*metabolism ; Sequence Alignment ; *Signal Transduction ; Viral Proteins/genetics/metabolism
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  • 43
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-05-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marshall, E -- Normile, D -- New York, N.Y. -- Science. 2001 May 18;292(5520):1274-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11360967" target="_blank"〉PubMed〈/a〉
    Keywords: *Alzheimer Disease/economics/genetics/pathology ; Biomedical Research ; Cell Line ; DNA/economics ; Government Agencies ; Intellectual Property ; Japan ; Ownership/economics/legislation & jurisprudence ; Research Personnel/*legislation & jurisprudence ; Theft/economics/*legislation & jurisprudence ; United States
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  • 44
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-05-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Davenport, R J -- New York, N.Y. -- Science. 2001 May 25;292(5521):1469-71.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11379615" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caenorhabditis elegans/genetics ; Cell Line ; Drosophila melanogaster/genetics ; *Gene Silencing ; Humans ; Protein Biosynthesis ; RNA, Double-Stranded/*genetics ; RNA, Messenger/metabolism
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  • 45
    Publication Date: 2001-07-28
    Description: Although the biological actions of the cell membrane and serum lipid lysophosphatidylcholine (LPC) in atherosclerosis and systemic autoimmune disease are well recognized, LPC has not been linked to a specific cell-surface receptor. We show that LPC is a high-affinity ligand for G2A, a lymphocyte-expressed G protein-coupled receptor whose genetic ablation results in the development of autoimmunity. Activation of G2A by LPC increased intracellular calcium concentration, induced receptor internalization, activated ERK mitogen-activated protein kinase, and modified migratory responses of Jurkat T lymphocytes. This finding implicates a role for LPC-G2A interaction in the etiology of inflammatory autoimmune disease and atherosclerosis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kabarowski, J H -- Zhu, K -- Le, L Q -- Witte, O N -- Xu, Y -- 1 R21 CA84038-01/CA/NCI NIH HHS/ -- CA76204/CA/NCI NIH HHS/ -- T32 CA09056/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2001 Jul 27;293(5530):702-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, Immunology, and Molecular Genetics, Lerner Research Institute, 9500 Euclid Avenue, Cleveland, OH 44195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11474113" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arteriosclerosis/immunology/metabolism ; Calcium/metabolism ; Cell Cycle Proteins/*metabolism ; Cell Line ; Chemotaxis, Leukocyte ; Humans ; Jurkat Cells ; Ligands ; Lupus Erythematosus, Systemic/immunology/metabolism ; Lymphocyte Activation ; Lysophosphatidylcholines/*metabolism/pharmacology ; Mitogen-Activated Protein Kinases/metabolism ; Phosphorylcholine/analogs & derivatives/metabolism/pharmacology ; Radioligand Assay ; Receptors, Cell Surface/*metabolism ; *Receptors, G-Protein-Coupled ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; Sphingosine/analogs & derivatives/metabolism/pharmacology ; T-Lymphocytes/immunology/*metabolism/physiology ; Tetradecanoylphorbol Acetate/pharmacology ; Transfection ; Virulence Factors, Bordetella/pharmacology
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  • 46
    Publication Date: 2001-07-07
    Description: The existence of a large number of receptors coupled to heterotrimeric guanine nucleotide binding proteins (G proteins) raises the question of how a particular receptor selectively regulates specific targets. We provide insight into this question by identifying a prototypical macromolecular signaling complex. The beta(2) adrenergic receptor was found to be directly associated with one of its ultimate effectors, the class C L-type calcium channel Ca(v)1.2. This complex also contained a G protein, an adenylyl cyclase, cyclic adenosine monophosphate-dependent protein kinase, and the counterbalancing phosphatase PP2A. Our electrophysiological recordings from hippocampal neurons demonstrate highly localized signal transduction from the receptor to the channel. The assembly of this signaling complex provides a mechanism that ensures specific and rapid signaling by a G protein-coupled receptor.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Davare, M A -- Avdonin, V -- Hall, D D -- Peden, E M -- Burette, A -- Weinberg, R J -- Horne, M C -- Hoshi, T -- Hell, J W -- AG00213/AG/NIA NIH HHS/ -- AG17502/AG/NIA NIH HHS/ -- GM08688/GM/NIGMS NIH HHS/ -- GM56900/GM/NIGMS NIH HHS/ -- HL61645/HL/NHLBI NIH HHS/ -- NS35563/NS/NINDS NIH HHS/ -- NS39444/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2001 Jul 6;293(5527):98-101.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of Wisconsin, Madison, WI 53706, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11441182" target="_blank"〉PubMed〈/a〉
    Keywords: Adenylyl Cyclases/metabolism ; Adrenergic beta-2 Receptor Agonists ; Albuterol/pharmacology ; Animals ; Calcium Channels, L-Type/genetics/*metabolism ; Cell Line ; Cell Membrane/metabolism ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Electric Conductivity ; Fluorescent Antibody Technique ; Heterotrimeric GTP-Binding Proteins/metabolism ; Humans ; Isoproterenol/pharmacology ; Kinetics ; Macromolecular Substances ; Neurons/cytology/drug effects/enzymology/metabolism ; Phosphoprotein Phosphatases/metabolism ; Precipitin Tests ; Prosencephalon/cytology/metabolism ; Protein Binding ; Pyramidal Cells/cytology/drug effects/enzymology/metabolism ; Rats ; Receptors, Adrenergic, beta-2/genetics/*metabolism ; *Signal Transduction ; Substrate Specificity
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  • 47
    Publication Date: 2001-05-26
    Description: Intracellular deposition of aggregated and ubiquitylated proteins is a prominent cytopathological feature of most neurodegenerative disorders. Whether protein aggregates themselves are pathogenic or are the consequence of an underlying molecular lesion is unclear. Here, we report that protein aggregation directly impaired the function of the ubiquitin-proteasome system. Transient expression of two unrelated aggregation-prone proteins, a huntingtin fragment containing a pathogenic polyglutamine repeat and a folding mutant of cystic fibrosis transmembrane conductance regulator, caused nearly complete inhibition of the ubiquitin-proteasome system. Because of the central role of ubiquitin-dependent proteolysis in regulating fundamental cellular events such as cell division and apoptosis, our data suggest a potential mechanism linking protein aggregation to cellular disregulation and cell death.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bence, N F -- Sampat, R M -- Kopito, R R -- New York, N.Y. -- Science. 2001 May 25;292(5521):1552-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Stanford University, Stanford, CA 94305-5020, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11375494" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylcysteine/*analogs & derivatives/pharmacology ; Amino Acid Sequence ; Cell Death ; Cell Line ; Cysteine Endopeptidases/*metabolism ; Cysteine Proteinase Inhibitors/pharmacology ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics/*metabolism ; Endoplasmic Reticulum/metabolism ; G2 Phase ; Green Fluorescent Proteins ; Humans ; Inclusion Bodies/metabolism ; Leupeptins/pharmacology ; Luminescent Proteins/genetics/metabolism ; Molecular Sequence Data ; Multienzyme Complexes/antagonists & inhibitors/*metabolism ; Nerve Tissue Proteins/genetics/*metabolism ; Nuclear Proteins/genetics/*metabolism ; Proteasome Endopeptidase Complex ; Recombinant Fusion Proteins/metabolism ; Transfection ; Ubiquitins/*metabolism
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  • 48
    Publication Date: 2001-02-27
    Description: The mammalian innate immune system retains from Drosophila a family of homologous Toll-like receptors (TLRs) that mediate responses to microbial ligands. Here, we show that TLR2 activation leads to killing of intracellular Mycobacterium tuberculosis in both mouse and human macrophages, through distinct mechanisms. In mouse macrophages, bacterial lipoprotein activation of TLR2 leads to a nitric oxide-dependent killing of intracellular tubercle bacilli, but in human monocytes and alveolar macrophages, this pathway was nitric oxide-independent. Thus, mammalian TLRs respond (as Drosophila Toll receptors do) to microbial ligands and also have the ability to activate antimicrobial effector pathways at the site of infection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thoma-Uszynski, S -- Stenger, S -- Takeuchi, O -- Ochoa, M T -- Engele, M -- Sieling, P A -- Barnes, P F -- Rollinghoff, M -- Bolcskei, P L -- Wagner, M -- Akira, S -- Norgard, M V -- Belisle, J T -- Godowski, P J -- Bloom, B R -- Modlin, R L -- AI 07118/AI/NIAID NIH HHS/ -- AI 22553/AI/NIAID NIH HHS/ -- AI 47868/AI/NIAID NIH HHS/ -- AR 40312/AR/NIAMS NIH HHS/ -- New York, N.Y. -- Science. 2001 Feb 23;291(5508):1544-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Dermatology, Department of Microbiology and Immunology and Molecular Biology Institute, UCLA School of Medicine, Los Angeles, CA 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11222859" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Proteins/immunology ; Cell Line ; Cells, Cultured ; *Drosophila Proteins ; Humans ; Interferon-gamma/immunology/pharmacology ; Ligands ; Lipoproteins/*immunology ; Macrophage Activation ; Macrophages/immunology/metabolism/*microbiology ; Macrophages, Alveolar/immunology/metabolism/microbiology ; Macrophages, Peritoneal/immunology/metabolism/microbiology ; Membrane Glycoproteins/*metabolism ; Mice ; Monocytes/immunology/metabolism/*microbiology ; Mycobacterium tuberculosis/growth & development/*immunology ; Nitric Oxide/*metabolism ; Nitric Oxide Synthase/antagonists & inhibitors/metabolism ; Nitric Oxide Synthase Type II ; Receptors, Cell Surface/*metabolism ; Signal Transduction ; Toll-Like Receptor 2 ; Toll-Like Receptors ; Tumor Necrosis Factor-alpha/immunology/pharmacology
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  • 49
    Publication Date: 2001-09-29
    Description: BERLIN AND MELBOURNE--After 2 years of deliberation, an Australian government committee has endorsed legislation that would allow both human embryonic stem cell research and the derivation of ES cells from unwanted embryos created during fertility treatments. And in Israel, another country at the forefront of work on ES cells, a national bioethics committee has approved both the derivation of ES cells and research into therapeutic cloning.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dayton, L -- Vogel, G -- New York, N.Y. -- Science. 2001 Sep 28;293(5539):2367-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11577208" target="_blank"〉PubMed〈/a〉
    Keywords: Australia ; Bioethics ; Cell Line ; *Cloning, Organism/legislation & jurisprudence ; *Embryo Research ; Embryo, Mammalian/*cytology ; Government Regulation ; Humans ; Israel ; Public Policy ; *Research/legislation & jurisprudence ; *Stem Cells
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  • 50
    Publication Date: 2001-02-07
    Description: Replicative senescence is thought to be an intrinsic mechanism for limiting the proliferative life-span of normal somatic cells. We show here that rat Schwann cells can be expanded indefinitely in culture while maintaining checkpoints normally lost during the immortalization process. These findings demonstrate that senescence is not an inevitable consequence of extended proliferation in culture.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mathon, N F -- Malcolm, D S -- Harrisingh, M C -- Cheng, L -- Lloyd, A C -- New York, N.Y. -- Science. 2001 Feb 2;291(5505):872-5. Epub 2001 Jan 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11157166" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood ; Carrier Proteins/metabolism ; *Cell Aging ; Cell Culture Techniques ; *Cell Division ; Cell Line ; Cell Size ; Cells, Cultured ; Clone Cells ; Culture Media ; Cyclin-Dependent Kinase Inhibitor p16 ; Cyclin-Dependent Kinases/metabolism ; Cyclins/metabolism ; Fibroblasts/cytology/physiology ; Giant Cells/cytology ; Mutation ; Phenotype ; Proteins/metabolism ; Rats ; Schwann Cells/*cytology/physiology ; Telomerase/metabolism ; Telomere/physiology ; Tumor Suppressor Protein p14ARF ; Tumor Suppressor Protein p53/metabolism ; beta-Galactosidase/metabolism ; ras Proteins/metabolism
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  • 51
    Publication Date: 2001-08-11
    Description: Double-stranded RNA induces potent and specific gene silencing through a process referred to as RNA interference (RNAi) or posttranscriptional gene silencing (PTGS). RNAi is mediated by RNA-induced silencing complex (RISC), a sequence-specific, multicomponent nuclease that destroys messenger RNAs homologous to the silencing trigger. RISC is known to contain short RNAs ( approximately 22 nucleotides) derived from the double-stranded RNA trigger, but the protein components of this activity are unknown. Here, we report the biochemical purification of the RNAi effector nuclease from cultured Drosophila cells. The active fraction contains a ribonucleoprotein complex of approximately 500 kilodaltons. Protein microsequencing reveals that one constituent of this complex is a member of the Argonaute family of proteins, which are essential for gene silencing in Caenorhabditis elegans, Neurospora, and Arabidopsis. This observation begins the process of forging links between genetic analysis of RNAi from diverse organisms and the biochemical model of RNAi that is emerging from Drosophila in vitro systems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hammond, S M -- Boettcher, S -- Caudy, A A -- Kobayashi, R -- Hannon, G J -- R01-GM62534/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2001 Aug 10;293(5532):1146-50.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11498593" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Argonaute Proteins ; Cell Line ; Drosophila ; *Drosophila Proteins ; Endoribonucleases/metabolism ; *Gene Silencing ; Genes, Insect ; Insect Proteins/chemistry/genetics/isolation & purification/*metabolism ; Molecular Sequence Data ; Multigene Family ; Protein Structure, Tertiary ; RNA, Double-Stranded/genetics/*metabolism ; *RNA-Induced Silencing Complex ; Repetitive Sequences, Nucleic Acid ; Ribonuclease III ; Transfection
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  • 52
    Publication Date: 2001-09-05
    Description: Natriuretic peptides (NPs) are vasoactive cyclic-peptide hormones important in blood pressure regulation through interaction with natriuretic cell-surface receptors. We report the hormone-binding thermodynamics and crystal structures at 2.9 and 2.0 angstroms, respectively, of the extracellular domain of the unliganded human NP receptor (NPR-C) and its complex with CNP, a 22-amino acid NP. A single CNP molecule is bound in the interface of an NPR-C dimer, resulting in asymmetric interactions between the hormone and the symmetrically related receptors. Hormone binding induces a 20 angstrom closure between the membrane-proximal domains of the dimer. In each monomer, the opening of an interdomain cleft, which is tethered together by a linker peptide acting as a molecular spring, is likely a conserved allosteric trigger for intracellular signaling by the natriuretic receptor family.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉He Xl -- Chow Dc -- Martick, M M -- Garcia, K C -- New York, N.Y. -- Science. 2001 Aug 31;293(5535):1657-62.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Microbiology and Immunology and Structural Biology, Stanford University School of Medicine, Fairchild D319, 299 Campus Drive, Stanford, CA 93405-5124, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11533490" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Amino Acid Sequence ; Animals ; Atrial Natriuretic Factor/metabolism ; Binding Sites ; Calorimetry ; Cell Line ; Chlorides/metabolism ; Crystallization ; Crystallography, X-Ray ; Dimerization ; Drosophila ; Glycosylation ; Guanylate Cyclase/*chemistry/*metabolism ; Humans ; Hydrogen Bonding ; Ligands ; Models, Molecular ; Molecular Sequence Data ; Natriuretic Peptide, Brain/metabolism ; Natriuretic Peptide, C-Type/chemistry/*metabolism ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Receptors, Atrial Natriuretic Factor/*chemistry/*metabolism ; Thermodynamics
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  • 53
    Publication Date: 2001-02-27
    Description: As an organelle coupling nuclear and cytoplasmic divisions, the centrosome is essential to mitotic fidelity, and its inheritance could be critical to understanding cell transformation. Investigating the behavior of the centrosome in living mitotic cells, we documented a transient and remarkable postanaphase repositioning of this organelle, which apparently controls the release of central microtubules from the midbody and the completion of cell division. We also observed that the absence of the centrosome leads to defects in cytokinesis. Together with recent results in yeasts, our data point to a conserved centrosome-dependent pathway that integrates spatial controls into the decision of completing cell division, which requires the repositioning of the centrosome organelle.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Piel, M -- Nordberg, J -- Euteneuer, U -- Bornens, M -- New York, N.Y. -- Science. 2001 Feb 23;291(5508):1550-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut Curie, Section Recherche, UMR 144 du CNRS, 26 rue d'Ulm, 75248 Paris Cedex 05, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11222861" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Animals ; Calcium-Binding Proteins/metabolism ; Cell Adhesion ; Cell Division/*physiology ; Cell Line ; Centrioles/*physiology ; Centrosome/*physiology/ultrastructure ; *Chromosomal Proteins, Non-Histone ; HeLa Cells ; Humans ; Metaphase ; Mice ; Microscopy, Fluorescence ; Microscopy, Phase-Contrast ; Microscopy, Video ; Microtubules/drug effects/physiology/ultrastructure ; Mitosis ; Models, Biological ; Nocodazole/pharmacology ; Recombinant Fusion Proteins/metabolism ; Spindle Apparatus/physiology/ultrastructure ; Telophase
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  • 54
    Publication Date: 2001-12-12
    Description: Calcium (Ca2+) influx through Ca2+-permeable ion channels plays a pivotal role in a variety of neuronal signaling processes, and negative-feedback control of this influx by Ca2+ itself is often equally important for modulation of such signaling. Negative modulation by Ca2+ through calmodulin (CaM) on cyclic nucleotide-gated (CNG) channels underlies the adaptation of olfactory receptor neurons to odorants. We show that this feedback requires two additional subunits of the native olfactory channel, CNGA4 and CNGB1b, even though the machinery for CaM binding and modulation is present in the principal subunit CNGA2. This provides a rationale for the presence of three distinct subunits in the native olfactory channel and underscores the subtle link between the molecular make-up of an ion channel and the physiological function it subserves.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bradley, J -- Reuter, D -- Frings, S -- New York, N.Y. -- Science. 2001 Dec 7;294(5549):2176-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut fur Biologische Informationsverarbeitung, Forschungszentrum Julich, 52425 Julich, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11739960" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptation, Physiological ; Animals ; Calcium/metabolism/pharmacology ; Calcium Signaling ; Calmodulin/*metabolism/pharmacology ; Cell Line ; Cyclic AMP/*metabolism ; Cyclic Nucleotide-Gated Cation Channels ; Feedback, Physiological ; Humans ; Ion Channel Gating ; Ion Channels/metabolism/*physiology ; Kinetics ; *Odors ; Olfactory Receptor Neurons/*physiology ; Patch-Clamp Techniques ; Photolysis ; Protein Subunits ; Rats ; Recombinant Proteins/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 55
    Publication Date: 2001-07-14
    Description: Interferons (IFN) alpha/beta and gamma induce the formation of two transcriptional activators: gamma-activating factor (GAF) and interferon-stimulated gamma factor 3 (ISGF3). We report a natural heterozygous germline STAT1 mutation associated with susceptibility to mycobacterial but not viral disease. This mutation causes a loss of GAF and ISGF3 activation but is dominant for one cellular phenotype and recessive for the other. It impairs the nuclear accumulation of GAF but not of ISGF3 in heterozygous cells stimulated by IFNs. Thus, the antimycobacterial, but not the antiviral, effects of human IFNs are principally mediated by GAF.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dupuis, S -- Dargemont, C -- Fieschi, C -- Thomassin, N -- Rosenzweig, S -- Harris, J -- Holland, S M -- Schreiber, R D -- Casanova, J L -- New York, N.Y. -- Science. 2001 Jul 13;293(5528):300-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratoire de Genetique Humaine des Maladies Infectieuses, Universite de Paris Rene Descartes-INSERM UMR550, Faculte de Medecine Necker-Enfants Malades, 75015 Paris, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11452125" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animals ; Cell Line ; Child ; Child, Preschool ; DNA/metabolism ; DNA-Binding Proteins/genetics/*physiology ; Female ; Fibroblasts/metabolism/virology ; Gene Expression Regulation ; *Germ-Line Mutation ; Humans ; *Immunity/genetics ; Interferon-Stimulated Gene Factor 3 ; Interferon-Stimulated Gene Factor 3, gamma Subunit ; Interferon-alpha/*immunology/metabolism ; Interferon-gamma/*immunology/metabolism ; Janus Kinase 1 ; Mice ; Mycobacterium Infections/genetics/*immunology ; Mycobacterium avium Complex/immunology ; Mycobacterium avium-intracellulare Infection/genetics/immunology ; Mycobacterium bovis ; Pedigree ; Protein Binding ; Protein-Tyrosine Kinases/genetics ; STAT1 Transcription Factor ; Signal Transduction ; Simian virus 40 ; Trans-Activators/genetics/*physiology ; Transcription Factors/physiology ; Virus Diseases/genetics/*immunology
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  • 56
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-08-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vogel, G -- New York, N.Y. -- Science. 2001 Aug 17;293(5533):1242-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11509703" target="_blank"〉PubMed〈/a〉
    Keywords: Bioethics ; Cell Line ; *Embryo Research ; Embryo, Mammalian/*cytology ; Financing, Government ; Guidelines as Topic ; Humans ; Internationality ; National Institutes of Health (U.S.) ; Politics ; Public Policy ; Research ; Research Embryo Creation ; *Research Support as Topic ; *Stem Cells ; United States
    Print ISSN: 0036-8075
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  • 57
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-07-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vogel, G -- New York, N.Y. -- Science. 2001 Jul 20;293(5529):413.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11463891" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animals ; Cell Line ; Embryo, Mammalian/cytology ; Humans ; *National Institutes of Health (U.S.) ; Paralysis/therapy ; Rats ; *Research ; *Stem Cells ; United States
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 58
    Publication Date: 2001-07-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vogel, G -- New York, N.Y. -- Science. 2001 Jul 13;293(5528):186-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11452086" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; *Embryo Research ; Embryo, Mammalian/cytology ; Financing, Government ; Government ; Humans ; National Institutes of Health (U.S.) ; Politics ; Research/economics/*legislation & jurisprudence ; Research Support as Topic ; *Stem Cells ; United States
    Print ISSN: 0036-8075
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  • 59
    Publication Date: 2001-07-07
    Description: Neuronal PAS domain protein 2 (NPAS2) is a transcription factor expressed primarily in the mammalian forebrain. NPAS2 is highly related in primary amino acid sequence to Clock, a transcription factor expressed in the suprachiasmatic nucleus that heterodimerizes with BMAL1 and regulates circadian rhythm. To investigate the biological role of NPAS2, we prepared a neuroblastoma cell line capable of conditional induction of the NPAS2:BMAL1 heterodimer and identified putative target genes by representational difference analysis, DNA microarrays, and Northern blotting. Coinduction of NPAS2 and BMAL1 activated transcription of the endogenous Per1, Per2, and Cry1 genes, which encode negatively activating components of the circadian regulatory apparatus, and repressed transcription of the endogenous BMAL1 gene. Analysis of the frontal cortex of wild-type mice kept in a 24-hour light-dark cycle revealed that Per1, Per2, and Cry1 mRNA levels were elevated during darkness and reduced during light, whereas BMAL1 mRNA displayed the opposite pattern. In situ hybridization assays of mice kept in constant darkness revealed that Per2 mRNA abundance did not oscillate as a function of the circadian cycle in NPAS2-deficient mice. Thus, NPAS2 likely functions as part of a molecular clock operative in the mammalian forebrain.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reick, M -- Garcia, J A -- Dudley, C -- McKnight, S L -- 1RO1MH59388/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2001 Jul 20;293(5529):506-9. Epub 2001 Jul 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11441147" target="_blank"〉PubMed〈/a〉
    Keywords: ARNTL Transcription Factors ; Amino Acid Sequence ; Animals ; Basic Helix-Loop-Helix Transcription Factors ; Biological Clocks/*physiology ; Blotting, Northern ; CLOCK Proteins ; Cell Cycle Proteins ; Cell Line ; Circadian Rhythm/*physiology ; Cloning, Molecular ; Cryptochromes ; Darkness ; Dimerization ; *Drosophila Proteins ; Ecdysterone/*analogs & derivatives/pharmacology ; *Eye Proteins ; Flavoproteins/genetics/metabolism ; Gene Expression Regulation ; Humans ; In Situ Hybridization ; Light ; Mice ; Mice, Inbred Strains ; Molecular Sequence Data ; Nerve Tissue Proteins/chemistry/genetics/*metabolism ; Nuclear Proteins/genetics/metabolism ; Oligonucleotide Array Sequence Analysis ; Period Circadian Proteins ; *Photoreceptor Cells, Invertebrate ; Prosencephalon/*metabolism ; Receptors, G-Protein-Coupled ; Trans-Activators/chemistry/metabolism ; Transcription Factors/chemistry/genetics/*metabolism ; Transfection ; Tumor Cells, Cultured
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  • 60
    Publication Date: 2001-06-02
    Description: The delivery of soluble hydrolases to lysosomes is mediated by the cation-independent and cation-dependent mannose 6-phosphate receptors. The cytosolic tails of both receptors contain acidic-cluster-dileucine signals that direct sorting from the trans-Golgi network to the endosomal-lysosomal system. We found that these signals bind to the VHS domain of the Golgi-localized, gamma-ear-containing, ARF-binding proteins (GGAs). The receptors and the GGAs left the trans-Golgi network on the same tubulo-vesicular carriers. A dominant-negative GGA mutant blocked exit of the receptors from the trans-Golgi network. Thus, the GGAs appear to mediate sorting of the mannose 6-phosphate receptors at the trans-Golgi network.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Puertollano, R -- Aguilar, R C -- Gorshkova, I -- Crouch, R J -- Bonifacino, J S -- New York, N.Y. -- Science. 2001 Jun 1;292(5522):1712-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11387475" target="_blank"〉PubMed〈/a〉
    Keywords: ADP-Ribosylation Factors/chemistry/genetics/*metabolism ; *Adaptor Proteins, Vesicular Transport ; Amino Acid Motifs ; Amino Acid Sequence ; Animals ; COS Cells ; Carrier Proteins/chemistry/genetics/*metabolism ; Cations ; Cell Line ; Clathrin/metabolism ; Dipeptides/chemistry/metabolism ; Dogs ; Humans ; Microscopy, Fluorescence ; Molecular Sequence Data ; Mutation ; Protein Sorting Signals ; Protein Structure, Tertiary ; Protein Transport ; Proteins/chemistry/genetics/*metabolism ; Receptor, IGF Type 2/chemistry/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Transport Vesicles/metabolism ; Two-Hybrid System Techniques ; Yeasts ; trans-Golgi Network/*metabolism
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  • 61
    Publication Date: 2001-12-01
    Description: The transport of messenger RNAs (mRNAs) from the nucleus to the cytoplasm involves adapter proteins that bind the mRNA as well as receptor proteins that interact with the nuclear pore complex. We demonstrate the utility of cell-permeable peptides designed to interfere with interactions between potential adapter and receptor proteins to define the pathways accessed by particular mRNAs. We show that HuR, a protein implicated in the stabilization of short-lived mRNAs containing AU-rich elements (AREs), serves as an adapter for c-fos mRNA export through two pathways. One involves the HuR shuttling domain, HNS, which exhibits a heat shock-sensitive interaction with transportin 2 (Trn2); the other involves two protein ligands of HuR-pp32 and APRIL-which contain leucine-rich nuclear export signals (NES) recognized by the export receptor CRM1. Heterokaryon and in situ hybridization experiments reveal that the peptides selectively block the nucleocytoplasmic shuttling of their respective adapter proteins without perturbing the overall cellular distribution of polyadenylated mRNAs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gallouzi, I E -- Steitz, J A -- CA16038/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2001 Nov 30;294(5548):1895-901.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11729309" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antennapedia Homeodomain Protein ; *Antigens, Surface ; Biological Transport/drug effects ; Cell Line ; *Cell Membrane Permeability ; Cell Nucleus/drug effects/*metabolism ; Cytoplasm/drug effects/*metabolism ; ELAV Proteins ; ELAV-Like Protein 1 ; Genes, fos/*genetics ; Heat-Shock Response ; Homeodomain Proteins/chemistry/metabolism ; Humans ; Karyopherins/metabolism ; Molecular Sequence Data ; Neuropeptides/chemistry/metabolism ; Nuclear Proteins/chemistry/metabolism ; Peptide Fragments/*metabolism/pharmacology ; Phosphoproteins/metabolism ; Protein Binding/drug effects ; Protein Structure, Tertiary ; RNA Stability ; RNA, Messenger/genetics/*metabolism ; RNA-Binding Proteins/antagonists & inhibitors/chemistry/*metabolism ; *Receptors, Cytoplasmic and Nuclear ; Regulatory Sequences, Nucleic Acid/genetics ; Reproducibility of Results ; Tetrahydrofolate Dehydrogenase/genetics ; *Transcription Factors
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  • 62
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-08-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Normile, D -- New York, N.Y. -- Science. 2001 Aug 3;293(5531):775.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11486059" target="_blank"〉PubMed〈/a〉
    Keywords: Bioethics ; Cell Line ; *Embryo Research ; Embryo, Mammalian/*cytology ; *Guidelines as Topic ; Humans ; Japan ; Public Policy ; *Research ; *Stem Cells
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  • 63
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-02-24
    Description: In animal models, injected stem cells travel to tissue injured by stroke, Alzheimer's-like plaques, contusions, or spinal cord bruises, sometimes traversing long distances. Several teams reported these surprising results this month at the Society for Neuroscience annual meeting. No one knows exactly how stem cells detect these different kinds of damage, but researchers hope that the cells' migratory powers can be harnessed to either replace dead tissue or deliver therapeutics right where they're needed.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Helmuth, L -- New York, N.Y. -- Science. 2000 Nov 24;290(5496):1479-81.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11185499" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/physiology ; Brain/*pathology ; Brain Neoplasms/pathology/therapy ; Cell Line ; Cell Movement ; Central Nervous System Diseases/pathology/*therapy ; Embryo, Mammalian/cytology ; Humans ; Myelin Sheath/physiology ; Neuroglia/cytology/physiology ; Neurons/*cytology/physiology ; Spinal Cord/*pathology ; *Stem Cell Transplantation ; Stem Cells/*physiology
    Print ISSN: 0036-8075
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  • 64
    Publication Date: 2001-03-07
    Description: The ability of intestinal mucosa to absorb dietary ferric iron is attributed to the presence of a brush-border membrane reductase activity that displays adaptive responses to iron status. We have isolated a complementary DNA, Dcytb (for duodenal cytochrome b), which encoded a putative plasma membrane di-heme protein in mouse duodenal mucosa. Dcytb shared between 45 and 50% similarity to the cytochrome b561 family of plasma membrane reductases, was highly expressed in the brush-border membrane of duodenal enterocytes, and induced ferric reductase activity when expressed in Xenopus oocytes and cultured cells. Duodenal expression levels of Dcytb messenger RNA and protein were regulated by changes in physiological modulators of iron absorption. Thus, Dcytb provides an important element in the iron absorption pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McKie, A T -- Barrow, D -- Latunde-Dada, G O -- Rolfs, A -- Sager, G -- Mudaly, E -- Mudaly, M -- Richardson, C -- Barlow, D -- Bomford, A -- Peters, T J -- Raja, K B -- Shirali, S -- Hediger, M A -- Farzaneh, F -- Simpson, R J -- New York, N.Y. -- Science. 2001 Mar 2;291(5509):1755-9. Epub 2001 Feb 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Medicine, Guy's, King's and St. Thomas' School of Medicine, King's College London, Rayne Institute, Denmark Hill Campus, 123 Coldharbour Lane, London SE5 9NU, UK. andrew.t.mckie@kcl.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11230685" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Anemia/enzymology ; Animals ; Anoxia ; Cell Line ; Cloning, Molecular ; Cytochrome b Group/chemistry/genetics/*metabolism ; DNA, Complementary ; Duodenum/enzymology/*metabolism ; Enterocytes/enzymology/metabolism ; Enzyme Induction ; Ferric Compounds/*metabolism ; *Intestinal Absorption ; Intestinal Mucosa/enzymology/*metabolism ; Iron, Dietary/administration & dosage/*metabolism ; Male ; Mice ; Microvilli/enzymology/metabolism ; Molecular Sequence Data ; Nitroblue Tetrazolium/metabolism ; Oocytes ; Oxidation-Reduction ; Oxidoreductases/chemistry/genetics/*metabolism ; RNA, Messenger/genetics/metabolism ; Tetrazolium Salts/metabolism ; Thiazoles/metabolism ; *Transfection ; Up-Regulation ; Xenopus
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  • 65
    Publication Date: 2001-06-30
    Description: Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the progressive accumulation in selected neurons of protein inclusions containing alpha-synuclein and ubiquitin. Rare inherited forms of PD are caused by autosomal dominant mutations in alpha-synuclein or by autosomal recessive mutations in parkin, an E3 ubiquitin ligase. We hypothesized that these two gene products interact functionally, namely, that parkin ubiquitinates alpha-synuclein normally and that this process is altered in autosomal recessive PD. We have now identified a protein complex in normal human brain that includes parkin as the E3 ubiquitin ligase, UbcH7 as its associated E2 ubiquitin conjugating enzyme, and a new 22-kilodalton glycosylated form of alpha-synuclein (alphaSp22) as its substrate. In contrast to normal parkin, mutant parkin associated with autosomal recessive PD failed to bind alphaSp22. In an in vitro ubiquitination assay, alphaSp22 was modified by normal but not mutant parkin into polyubiquitinated, high molecular weight species. Accordingly, alphaSp22 accumulated in a non-ubiquitinated form in parkin-deficient PD brains. We conclude that alphaSp22 is a substrate for parkin's ubiquitin ligase activity in normal human brain and that loss of parkin function causes pathological alphaSp22 accumulation. These findings demonstrate a critical biochemical reaction between the two PD-linked gene products and suggest that this reaction underlies the accumulation of ubiquitinated alpha-synuclein in conventional PD.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shimura, H -- Schlossmacher, M G -- Hattori, N -- Frosch, M P -- Trockenbacher, A -- Schneider, R -- Mizuno, Y -- Kosik, K S -- Selkoe, D J -- NS 02127/NS/NINDS NIH HHS/ -- NS 38375/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2001 Jul 13;293(5528):263-9. Epub 2001 Jun 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11431533" target="_blank"〉PubMed〈/a〉
    Keywords: Brain/enzymology/*metabolism ; Brain Stem/enzymology/metabolism ; Cell Line ; Detergents ; Freezing ; Glycosylation ; Humans ; Lewy Bodies/enzymology/metabolism ; Ligases/genetics/*metabolism ; Mutation, Missense ; Nerve Tissue Proteins/*metabolism ; Parkinson Disease/enzymology/genetics/*metabolism ; Parkinsonian Disorders/enzymology/genetics/metabolism ; Substrate Specificity ; Synucleins ; *Ubiquitin-Conjugating Enzymes ; *Ubiquitin-Protein Ligases ; Ubiquitins/*metabolism ; alpha-Synuclein
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  • 66
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-10-13
    Description: Mammalian cells respond to changes in oxygen availability through a conserved pathway that is regulated by the hypoxia-inducible factor (HIF). The alpha subunit of HIF is targeted for degradation under normoxic conditions by a ubiquitin-ligase complex that recognizes a hydroxylated proline residue in HIF. We identified a conserved family of HIF prolyl hydoxylase (HPH) enzymes that appear to be responsible for this posttranslational modification. In cultured mammalian cells, inappropriate accumulation of HIF caused by forced expression of the HIF-1alpha subunit under normoxic conditions was attenuated by coexpression of HPH. Suppression of HPH in cultured Drosophila melanogaster cells by RNA interference resulted in elevated expression of a hypoxia-inducible gene (LDH, encoding lactate dehydrogenase) under normoxic conditions. These findings indicate that HPH is an essential component of the pathway through which cells sense oxygen.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bruick, R K -- McKnight, S L -- New York, N.Y. -- Science. 2001 Nov 9;294(5545):1337-40. Epub 2001 Oct 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard L3.124, Dallas, TX 75390-9152, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11598268" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Animals ; *Cell Hypoxia ; Cell Line ; Cloning, Molecular ; Conserved Sequence ; DNA-Binding Proteins/*metabolism ; Drosophila melanogaster/enzymology/genetics ; Gene Expression Regulation, Enzymologic ; Genes, Insect ; Genes, Reporter ; Humans ; Hydroxylation ; Hydroxyproline/metabolism ; Hypoxia-Inducible Factor 1 ; Hypoxia-Inducible Factor 1, alpha Subunit ; L-Lactate Dehydrogenase/genetics/metabolism ; Molecular Sequence Data ; Mutation ; Nuclear Proteins/*metabolism ; Oxygen/*metabolism ; Procollagen-Proline Dioxygenase/chemistry/genetics/*metabolism ; RNA, Double-Stranded/genetics ; Recombinant Proteins/metabolism ; Sequence Alignment ; Substrate Specificity ; *Transcription Factors ; Transfection
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  • 67
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-05-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vogel, G -- New York, N.Y. -- Science. 2001 May 25;292(5521):1463.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11379608" target="_blank"〉PubMed〈/a〉
    Keywords: Aborted Fetus ; Cell Line ; *Embryo Research ; Embryo, Mammalian/*cytology ; *Fetal Research ; Financing, Government ; Guidelines as Topic ; Humans ; National Institutes of Health (U.S.)/*legislation & jurisprudence ; *Research Support as Topic ; *Stem Cells ; United States ; United States Dept. of Health and Human Services/*legislation & jurisprudence
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  • 68
    Publication Date: 2001-08-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bush, G W -- New York, N.Y. -- Science. 2001 Aug 17;293(5533):1244-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11509705" target="_blank"〉PubMed〈/a〉
    Keywords: Bioethics ; Cell Line ; Cloning, Organism ; Embryo, Mammalian/*cytology ; Financing, Government ; Humans ; Life ; Public Policy ; *Research Support as Topic ; *Stem Cells ; United States
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  • 69
    Publication Date: 2001-02-27
    Description: Centrosomes were microsurgically removed from BSC-1 African green monkey kidney cells before the completion of S phase. Karyoplasts (acentrosomal cells) entered and completed mitosis. However, postmitotic karyoplasts arrested before S phase, whereas adjacent control cells divided repeatedly. Postmitotic karyoplasts assembled a microtubule-organizing center containing gamma-tubulin and pericentrin, but did not regenerate centrioles. These observations reveal the existence of an activity associated with core centrosomal structures-distinct from elements of the microtubule-organizing center-that is required for the somatic cell cycle to progress through G1 into S phase. Once the cell is in S phase, these core structures are not needed for the G2-M phase transition.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hinchcliffe, E H -- Miller, F J -- Cham, M -- Khodjakov, A -- Sluder, G -- R01 GM059363/GM/NIGMS NIH HHS/ -- R01 GM059363-02/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2001 Feb 23;291(5508):1547-50.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA., Laboratory of Cell Regulation, Wadsworth Center, Albany, NY 12201, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11222860" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens/metabolism ; Cell Division/drug effects ; Cell Line ; Centrioles/physiology ; Centrosome/*physiology ; Cercopithecus aethiops ; Cytoplasmic Granules/physiology/ultrastructure ; *G1 Phase ; Interphase ; Microscopy, Video ; Microtubule-Organizing Center/physiology ; Microtubules/physiology/ultrastructure ; Mitosis ; Paclitaxel/pharmacology ; *S Phase ; Spindle Apparatus/physiology/ultrastructure ; Tubulin/metabolism
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  • 70
    Publication Date: 2001-09-08
    Description: In mammalian cells, splice junctions play a dual role in mRNA quality control: They mediate selective nuclear export of mature mRNA and they serve as a mark for mRNA surveillance, which subjects aberrant mRNAs with premature termination codons to nonsense-mediated decay (NMD). Here, we demonstrate that the protein RNPS1, a component of the postsplicing complex that is deposited 5' to exon-exon junctions, interacts with the evolutionarily conserved human Upf complex, a central component of NMD. Significantly, RNPS1 triggers NMD when tethered to the 3' untranslated region of beta-globin mRNA, demonstrating its role as a subunit of the postsplicing complex directly involved in mRNA surveillance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lykke-Andersen, J -- Shu, M D -- Steitz, J A -- CA 16038/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2001 Sep 7;293(5536):1836-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Molecular Biochemistry and Biophysics, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11546874" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions/genetics/metabolism ; Animals ; Cell Line ; DNA-Binding Proteins/genetics/*metabolism ; Exons/*genetics ; Fungal Proteins/metabolism ; Globins/genetics ; HeLa Cells ; Humans ; Macromolecular Substances ; Mice ; Models, Biological ; Precipitin Tests ; Protein Binding ; RNA Helicases/metabolism ; RNA Splicing ; RNA, Messenger/genetics/*metabolism ; RNA-Binding Proteins/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; *Ribonucleoproteins ; Saccharomyces cerevisiae Proteins ; Trans-Activators ; Transfection
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  • 71
    Publication Date: 2001-12-01
    Description: The mammalian target of rapamycin (mTOR) governs cell growth and proliferation by mediating the mitogen- and nutrient-dependent signal transduction that regulates messenger RNA translation. We identified phosphatidic acid (PA) as a critical component of mTOR signaling. In our study, mitogenic stimulation of mammalian cells led to a phospholipase D-dependent accumulation of cellular PA, which was required for activation of mTOR downstream effectors. PA directly interacted with the domain in mTOR that is targeted by rapamycin, and this interaction was positively correlated with mTOR's ability to activate downstream effectors. The involvement of PA in mTOR signaling reveals an important function of this lipid in signal transduction and protein synthesis, as well as a direct link between mTOR and mitogens. Furthermore, these studies suggest a potential mechanism for the in vivo actions of the immunosuppressant rapamycin.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fang, Y -- Vilella-Bach, M -- Bachmann, R -- Flanigan, A -- Chen, J -- GM58064/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2001 Nov 30;294(5548):1942-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Structural Biology, University of Illinois at Urbana-Champaign, 601 South Goodwin Avenue, B107, Urbana, IL 61801, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11729323" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing ; Butanols/pharmacology ; Carrier Proteins/metabolism ; Cell Line ; Culture Media, Serum-Free ; Enzyme Activation/drug effects ; Humans ; Immunosuppressive Agents/pharmacology ; Mitogens/*pharmacology ; Phosphatidic Acids/*metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Phospholipase D/metabolism ; Phosphoproteins/metabolism ; Phosphorylation/drug effects ; Protein Binding ; Protein Kinases/chemistry/*metabolism ; Protein Structure, Tertiary ; Ribosomal Protein S6 Kinases/metabolism ; Signal Transduction/*drug effects ; Sirolimus/pharmacology ; TOR Serine-Threonine Kinases ; Time Factors
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 72
    Publication Date: 2001-03-10
    Description: To study the mechanisms underlying the high pathogenicity of Ebola virus, we have established a system that allows the recovery of infectious virus from cloned cDNA and thus permits genetic manipulation. We created a mutant in which the editing site of the gene encoding envelope glycoprotein (GP) was eliminated. This mutant no longer expressed the nonstructural glycoprotein sGP. Synthesis of GP increased, but most of it accumulated in the endoplasmic reticulum as immature precursor. The mutant was significantly more cytotoxic than wild-type virus, indicating that cytotoxicity caused by GP is down-regulated by the virus through transcriptional RNA editing and expression of sGP.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Volchkov, V E -- Volchkova, V A -- Muhlberger, E -- Kolesnikova, L V -- Weik, M -- Dolnik, O -- Klenk, H D -- New York, N.Y. -- Science. 2001 Mar 9;291(5510):1965-9. Epub 2001 Feb 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut fur Virologie, Philipps-Universitat, Robert-Koch-Strasse 17, 35037 Marburg, Germany. viktor.volchkov@ens-lyon.fr〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11239157" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cercopithecus aethiops ; Cloning, Molecular ; Cytopathogenic Effect, Viral ; DNA, Complementary ; Ebolavirus/*genetics/isolation & purification/*pathogenicity/physiology ; Glycoproteins/biosynthesis/chemistry/*genetics ; Mutation ; *RNA Editing ; Vero Cells ; Viral Envelope Proteins/chemistry/*genetics/metabolism ; *Viral Proteins ; Virulence ; Virus Replication
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  • 73
    Publication Date: 2001-07-07
    Description: Amyloid-beta precursor protein (APP), a widely expressed cell-surface protein, is cleaved in the transmembrane region by gamma-secretase. gamma-Cleavage of APP produces the extracellular amyloid beta-peptide of Alzheimer's disease and releases an intracellular tail fragment of unknown physiological function. We now demonstrate that the cytoplasmic tail of APP forms a multimeric complex with the nuclear adaptor protein Fe65 and the histone acetyltransferase Tip60. This complex potently stimulates transcription via heterologous Gal4- or LexA-DNA binding domains, suggesting that release of the cytoplasmic tail of APP by gamma-cleavage may function in gene expression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cao, X -- Sudhof, T C -- New York, N.Y. -- Science. 2001 Jul 6;293(5527):115-20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Center for Basic Neuroscience, Department of Molecular Genetics, and Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9111 USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11441186" target="_blank"〉PubMed〈/a〉
    Keywords: Acetyltransferases/chemistry/genetics/*metabolism ; Amyloid Precursor Protein Secretases ; Amyloid beta-Protein Precursor/*chemistry/genetics/*metabolism ; Animals ; Aspartic Acid Endopeptidases ; Bacterial Proteins/genetics/metabolism ; Cell Line ; DNA-Binding Proteins/chemistry/genetics/metabolism ; Endopeptidases/metabolism ; Fungal Proteins/genetics/metabolism ; Histone Acetyltransferases ; Humans ; Macromolecular Substances ; Mutation/genetics ; Nerve Tissue Proteins/chemistry/genetics/*metabolism ; Nuclear Proteins/chemistry/genetics/*metabolism ; Peptide Fragments/chemistry/genetics/metabolism ; Plasmids/genetics ; Precipitin Tests ; Protein Binding ; Protein Processing, Post-Translational ; Protein Structure, Tertiary ; Protein Transport ; Rats ; Recombinant Fusion Proteins/chemistry/genetics/metabolism ; *Saccharomyces cerevisiae Proteins ; Serine Endopeptidases/genetics/metabolism ; Transcription Factors/genetics/metabolism ; *Transcription, Genetic ; Transcriptional Activation ; Transfection ; Two-Hybrid System Techniques
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  • 74
    Publication Date: 2001-12-26
    Description: Kruppel-like factor 6 (KLF6) is a zinc finger transcription factor of unknown function. Here, we show that the KLF6 gene is mutated in a subset of human prostate cancer. Loss-of-heterozygosity analysis revealed that one KLF6 allele is deleted in 77% (17 of 22) of primary prostate tumors. Sequence analysis of the retained KLF6 allele revealed mutations in 71% of these tumors. Functional studies confirm that whereas wild-type KLF6 up-regulates p21 (WAF1/CIP1) in a p53-independent manner and significantly reduces cell proliferation, tumor-derived KLF6 mutants do not. Our data suggest that KLF6 is a tumor suppressor gene involved in human prostate cancer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Narla, G -- Heath, K E -- Reeves, H L -- Li, D -- Giono, L E -- Kimmelman, A C -- Glucksman, M J -- Narla, J -- Eng, F J -- Chan, A M -- Ferrari, A C -- Martignetti, J A -- Friedman, S L -- 5 P30 HD28822/HD/NICHD NIH HHS/ -- CA78207/CA/NCI NIH HHS/ -- CA79918/CA/NCI NIH HHS/ -- DK37340/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2001 Dec 21;294(5551):2563-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine, 1425 Madison Avenue, Room 1170F, Box 1123, New York, NY, 10029, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11752579" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Substitution ; Animals ; Cell Division ; Cell Line ; Chromosome Mapping ; Chromosomes, Human, Pair 10/genetics ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclins/genetics/metabolism ; *Genes, Tumor Suppressor ; Genetic Heterogeneity ; Humans ; Kruppel-Like Transcription Factors ; Loss of Heterozygosity ; Male ; Mice ; Microsatellite Repeats ; *Mutation ; Mutation, Missense ; Proliferating Cell Nuclear Antigen/metabolism ; Promoter Regions, Genetic ; Prostatic Neoplasms/*genetics ; *Proto-Oncogene Proteins ; Trans-Activators/chemistry/*genetics/physiology ; Transcriptional Activation ; Tumor Cells, Cultured ; Up-Regulation ; Zinc Fingers
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  • 75
    Publication Date: 2001-10-13
    Description: The PKB (protein kinase B, also called Akt) family of protein kinases plays a key role in insulin signaling, cellular survival, and transformation. PKB is activated by phosphorylation on residues threonine 308, by the protein kinase PDK1, and Serine 473, by a putative serine 473 kinase. Several protein binding partners for PKB have been identified. Here, we describe a protein partner for PKBalpha termed CTMP, or carboxyl-terminal modulator protein, that binds specifically to the carboxyl-terminal regulatory domain of PKBalpha at the plasma membrane. Binding of CTMP reduces the activity of PKBalpha by inhibiting phosphorylation on serine 473 and threonine 308. Moreover, CTMP expression reverts the phenotype of v-Akt-transformed cells examined under a number of criteria including cell morphology, growth rate, and in vivo tumorigenesis. These findings identify CTMP as a negative regulatory component of the pathway controlling PKB activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maira, S M -- Galetic, I -- Brazil, D P -- Kaech, S -- Ingley, E -- Thelen, M -- Hemmings, B A -- New York, N.Y. -- Science. 2001 Oct 12;294(5541):374-80.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Friedrich Miescher Institute, Post Office Box 2543, CH-4002 Basel, Switzerland., Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11598301" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptor Proteins, Signal Transducing ; Amino Acid Sequence ; Animals ; Carrier Proteins/chemistry/genetics/*metabolism ; Cell Division ; Cell Line ; Cell Line, Transformed ; Cell Membrane/*metabolism ; Cell Size ; Enzyme Activation ; Genes, fos ; Humans ; Insulin/pharmacology ; Insulin-Like Growth Factor I/pharmacology ; Membrane Proteins/chemistry/genetics/*metabolism ; Mice ; Mice, Nude ; Molecular Sequence Data ; Neoplasms, Experimental/etiology ; Oncogene Protein v-akt ; Phosphorylation ; Promoter Regions, Genetic ; Protein Binding ; Protein-Serine-Threonine Kinases/*metabolism ; *Proto-Oncogene Proteins ; Proto-Oncogene Proteins c-akt ; Recombinant Fusion Proteins/metabolism ; Retroviridae Proteins, Oncogenic/genetics/*metabolism ; Signal Transduction ; Thiolester Hydrolases ; Transcription, Genetic ; Transfection ; Tumor Cells, Cultured ; Vanadates/pharmacology
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  • 76
    Publication Date: 2001-09-05
    Description: The nuclear expression and action of the nuclear factor kappa B (NF-kappaB) transcription factor requires signal-coupled phosphorylation and degradation of the IkappaB inhibitors, which normally bind and sequester this pleiotropically active factor in the cytoplasm. The subsequent molecular events that regulate the termination of nuclear NF-kappaB action remain poorly defined, although the activation of de novo IkappaBalpha gene expression by NF-kappaB likely plays a key role. Our studies now demonstrate that the RelA subunit of NF-kappaB is subject to inducible acetylation and that acetylated forms of RelA interact weakly, if at all, with IkappaBalpha. Acetylated RelA is subsequently deacetylated through a specific interaction with histone deacetylase 3 (HDAC3). This deacetylation reaction promotes effective binding to IkappaBalpha and leads in turn to IkappaBalpha-dependent nuclear export of the complex through a chromosomal region maintenance-1 (CRM-1)-dependent pathway. Deacetylation of RelA by HDAC3 thus acts as an intranuclear molecular switch that both controls the duration of the NF-kappaB transcriptional response and contributes to the replenishment of the depleted cytoplasmic pool of latent NF-kappaB-IkappaBalpha complexes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen Lf -- Fischle, W -- Verdin, E -- Greene, W C -- P30MH59037/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2001 Aug 31;293(5535):1653-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gladstone Institute of Virology and Immunology, Department of Medicine, University of California, San Francisco, CA 94141, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11533489" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Acetyltransferases/metabolism ; Active Transport, Cell Nucleus ; Animals ; COS Cells ; CREB-Binding Protein ; Cell Cycle Proteins/metabolism ; Cell Line ; Cell Nucleus/*metabolism ; Cytoplasm/metabolism ; DNA/metabolism ; DNA-Binding Proteins/metabolism ; HeLa Cells ; Histone Acetyltransferases ; Histone Deacetylase Inhibitors ; Histone Deacetylases/metabolism ; Humans ; Hydroxamic Acids/pharmacology ; *I-kappa B Proteins ; Mice ; NF-kappa B/*metabolism ; Nuclear Proteins/metabolism ; Phosphorylation ; Protein Binding ; Protein Transport ; Recombinant Fusion Proteins/metabolism ; Trans-Activators/metabolism ; Transcription Factor RelA ; Transcription Factors ; Tumor Necrosis Factor-alpha/pharmacology ; p300-CBP Transcription Factors
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  • 77
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-12-18
    Description: There may be drugs and a useful vaccine available to combat the hepatitis B virus, but one aspect of this pathogen remains a puzzle: the function of its HBx protein. As Ganem reveals in his Perspective, new findings (Bouchard et al.) show that this versatile viral protein is an activator of calcium-dependent Ras signaling, an observation that may explain many of its biological effects.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ganem, D -- New York, N.Y. -- Science. 2001 Dec 14;294(5550):2299-300.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Departments of Medicine and Microbiology, University of California, San Francisco, CA 94143, USA. ganem@cgl.ucsf.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11743185" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/metabolism ; Calcium Signaling ; Cell Line ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; DNA Replication ; DNA, Viral/biosynthesis ; Focal Adhesion Kinase 2 ; Gene Expression Regulation, Viral ; Genes, Viral ; Hepatitis B virus/*genetics/*physiology ; Liver/virology ; Mutation ; Open Reading Frames ; Phosphorylation ; Protein-Tyrosine Kinases/genetics/metabolism ; Signal Transduction ; Trans-Activators/genetics/*metabolism ; Transcription Factor AP-1/metabolism ; Transcription Factors/metabolism ; Virus Replication ; ras Proteins/metabolism ; src-Family Kinases/metabolism
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  • 78
    Publication Date: 2001-09-29
    Description: Telomeres are specialized nucleoprotein structures that stabilize the ends of linear eukaryotic chromosomes. In mammalian cells, abrogation of telomeric repeat binding factor TRF2 or DNA-dependent protein kinase (DNA-PK) activity causes end-to-end chromosomal fusion, thus establishing an essential role for these proteins in telomere function. Here we show that TRF2-mediated end-capping occurs after telomere replication. The postreplicative requirement for TRF2 and DNA-PKcs, the catalytic subunit of DNA-PK, is confined to only half of the telomeres, namely, those that were produced by leading-strand DNA synthesis. These results demonstrate a crucial difference in postreplicative processing of telomeres that is linked to their mode of replication.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bailey, S M -- Cornforth, M N -- Kurimasa, A -- Chen, D J -- Goodwin, E H -- AG-917709/AG/NIA NIH HHS/ -- CA50519/CA/NCI NIH HHS/ -- CA76260/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2001 Sep 28;293(5539):2462-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87544, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11577237" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Division ; Cell Line ; Chromatids/physiology/ultrastructure ; Chromosomes/physiology/ultrastructure ; *DNA Replication ; DNA-Activated Protein Kinase ; DNA-Binding Proteins/genetics/*metabolism ; Humans ; In Situ Hybridization ; Mice ; Mitosis ; Mutation ; Nuclear Proteins ; Protein-Serine-Threonine Kinases/deficiency/metabolism ; Telomere/*metabolism ; Telomeric Repeat Binding Protein 2 ; Tumor Cells, Cultured
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  • 79
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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〉Normile, D -- New York, N.Y. -- Science. 2001 Aug 10;293(5532):1033.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11498559" target="_blank"〉PubMed〈/a〉
    Keywords: *Academies and Institutes ; Cell Line ; *Intellectual Property ; Japan ; Theft ; United States
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  • 80
    Publication Date: 2001-08-11
    Description: Cytokine receptors consist of multiple subunits, which are often shared between different receptors, resulting in the functional redundancy sometimes observed between cytokines. The interleukin 5 (IL-5) receptor consists of an IL-5-specific alpha-subunit (IL-5Ralpha) and a signal-transducing beta-subunit (betac) shared with the IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors. In this study, we sought to find a role for the cytoplasmic domain of IL-5Ralpha. We show that syntenin, a protein containing PSD-95/Discs large/zO-1 (PDZ) domains, associates with the cytoplasmic tail of the IL-5Ralpha. Syntenin was found to directly associate with the transcription factor Sox4. Association of syntenin with IL-5Ralpha was required for IL-5-mediated activation of Sox4. These studies identify a mechanism of transcriptional activation by cytokine-specific receptor subunits.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Geijsen, N -- Uings, I J -- Pals, C -- Armstrong, J -- McKinnon, M -- Raaijmakers, J A -- Lammers, J W -- Koenderman, L -- Coffer, P J -- New York, N.Y. -- Science. 2001 Aug 10;293(5532):1136-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pulmonary Diseases, Heart Lung Center Utrecht, University Medical Center, G03.550, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11498591" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Lymphocytes/immunology/*metabolism ; COS Cells ; Carrier Proteins/chemistry/*metabolism ; Cell Line ; Genes, Reporter ; High Mobility Group Proteins/*metabolism ; Humans ; Interleukin-5/*pharmacology ; *Intracellular Signaling Peptides and Proteins ; *Membrane Proteins ; Mice ; Mitogen-Activated Protein Kinases/metabolism ; Phosphorylation ; Point Mutation ; Protein Structure, Tertiary ; Receptors, Interleukin/chemistry/genetics/*metabolism ; Receptors, Interleukin-5 ; Recombinant Fusion Proteins/metabolism ; SOXC Transcription Factors ; Sequence Deletion ; Signal Transduction ; Syntenins ; Trans-Activators/*metabolism ; *Transcriptional Activation ; Transfection ; Two-Hybrid System Techniques
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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