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  • Cell Line  (116)
  • Temperature  (108)
  • Rats  (97)
  • Protein Conformation  (84)
  • American Association for the Advancement of Science (AAAS)  (373)
  • American Chemical Society
  • Cambridge University Press
  • 2000-2004  (373)
  • 1940-1944
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  • American Association for the Advancement of Science (AAAS)  (373)
  • American Chemical Society
  • Cambridge University Press
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  • 1
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    Prevention of chemotherapy-induced alopecia in rats by CDK inhibitors (2001)
    American Association for the Advancement of Science (AAAS)
    Details
    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
    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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  • 2
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    Collapse of the California Current during glacial maxima linked to climate change on land (2001)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2001-07-07
    Description: Time series of alkenone unsaturation indices gathered along the California margin reveal large (4 degrees to 8 degrees C) glacial-interglacial changes in sea surface temperature (SST) over the past 550,000 years. Interglacial times with SSTs equal to or exceeding that of the Holocene contain peak abundances in the pollen of redwood, the distinctive component of the temperate rainforest of the northwest coast of California. In the region now dominated by the California Current, SSTs warmed 10,000 to 15,000 years in advance of deglaciation at each of the past five glacial maxima. SSTs did not rise in advance of deglaciation south of the modern California Current front. Glacial warming along the California margin therefore is a regional signal of the weakening of the California Current during times when large ice sheets reorganized wind systems over the North Pacific. Both the timing and magnitude of the SST estimates suggest that the Devils Hole (Nevada) calcite record represents regional but not global paleotemperatures, and hence does not pose a fundamental challenge to the orbital ("Milankovitch") theory of the Ice Ages.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Herbert, T D -- Schuffert, J D -- Andreasen, D -- Heusser, L -- Lyle, M -- Mix, A -- Ravelo, A C -- Stott, L D -- Herguera, J C -- New York, N.Y. -- Science. 2001 Jul 6;293(5527):71-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Geological Sciences, Brown University, Providence, RI 02912, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11441174" target="_blank"〉PubMed〈/a〉
    Keywords: Calcium Carbonate ; California ; *Climate ; Diatoms/physiology ; *Ice ; Models, Biological ; Nevada ; Pacific Ocean ; Pollen ; *Seawater/analysis ; Temperature ; Trees/physiology
    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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  • 3
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    Observations of comet 19P/Borrelly by the miniature integrated camera and spectrometer aboard Deep Space 1 (2002)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2002-04-06
    Description: The nucleus of the Jupiter-family comet 19P/Borrelly was closely observed by the Miniature Integrated Camera and Spectrometer aboard the Deep Space 1 spacecraft on 22 September 2001. The 8-kilometer-long body is highly variegated on a scale of 200 meters, exhibiting large albedo variations (0.01 to 0.03) and complex geologic relationships. Short-wavelength infrared spectra (1.3 to 2.6 micrometers) show a slope toward the red and a hot, dry surface (〈/=345 kelvin, with no trace of water ice or hydrated minerals), consistent with approximately 10% or less of the surface actively sublimating. Borrelly's coma exhibits two types of dust features: fans and highly collimated jets. At encounter, the near-nucleus coma was dominated by a prominent dust jet that resolved into at least three smaller jets emanating from a broad basin in the middle of the nucleus. Because the major dust jet remained fixed in orientation, it is evidently aligned near the rotation axis of the nucleus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Soderblom, L A -- Becker, T L -- Bennett, G -- Boice, D C -- Britt, D T -- Brown, R H -- Buratti, B J -- Isbell, C -- Giese, B -- Hare, T -- Hicks, M D -- Howington-Kraus, E -- Kirk, R L -- Lee, M -- Nelson, R M -- Oberst, J -- Owen, T C -- Rayman, M D -- Sandel, B R -- Stern, S A -- Thomas, N -- Yelle, R V -- New York, N.Y. -- Science. 2002 May 10;296(5570):1087-91. Epub 2002 Apr 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉United States Geological Survey, 2255 North Gemini Drive, Flagstaff, AZ 86001, USA. lsoderblom@usgs.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11934989" target="_blank"〉PubMed〈/a〉
    Keywords: Carbon/analysis ; Cosmic Dust ; Hydrocarbons/analysis ; *Meteoroids ; Spectrum Analysis ; Temperature
    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
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    Jupiter's atmospheric composition from the Cassini thermal infrared spectroscopy experiment (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-08-21
    Description: The Composite Infrared Spectrometer observed Jupiter in the thermal infrared during the swing-by of the Cassini spacecraft. Results include the detection of two new stratospheric species, the methyl radical and diacetylene, gaseous species present in the north and south auroral infrared hot spots; determination of the variations with latitude of acetylene and ethane, the latter a tracer of atmospheric motion; observations of unexpected spatial distributions of carbon dioxide and hydrogen cyanide, both considered to be products of comet Shoemaker-Levy 9 impacts; characterization of the morphology of the auroral infrared hot spot acetylene emission; and a new evaluation of the energetics of the northern auroral infrared hot spot.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kunde, V G -- Flasar, F M -- Jennings, D E -- Bezard, B -- Strobel, D F -- Conrath, B J -- Nixon, C A -- Bjoraker, G L -- Romani, P N -- Achterberg, R K -- Simon-Miller, A A -- Irwin, P -- Brasunas, J C -- Pearl, J C -- Smith, M D -- Orton, G S -- Gierasch, P J -- Spilker, L J -- Carlson, R C -- Mamoutkine, A A -- Calcutt, S B -- Read, P L -- Taylor, F W -- Fouchet, T -- Parrish, P -- Barucci, A -- Courtin, R -- Coustenis, A -- Gautier, D -- Lellouch, E -- Marten, A -- Prange, R -- Biraud, Y -- Ferrari, C -- Owen, T C -- Abbas, M M -- Samuelson, R E -- Raulin, F -- Ade, P -- Cesarsky, C J -- Grossman, K U -- Coradini, A -- New York, N.Y. -- Science. 2004 Sep 10;305(5690):1582-6. Epub 2004 Aug 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Astronomy, University of Maryland, College Park, MD 20742, USA. Virgil.G.Kunde.1@gsfc.nasa.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15319491" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylene ; Atmosphere ; *Carbon Dioxide ; Ethane ; Extraterrestrial Environment ; *Hydrocarbons ; *Hydrogen Cyanide ; *Jupiter ; Spacecraft ; Spectrum Analysis ; Temperature
    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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  • 5
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    Initial results from the Mini-TES experiment in Gusev Crater from the Spirit Rover (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-08-07
    Description: The Miniature Thermal Emission Spectrometer (Mini-TES) on Spirit has studied the mineralogy and thermophysical properties at Gusev crater. Undisturbed soil spectra show evidence for minor carbonates and bound water. Rocks are olivinerich basalts with varying degrees of dust and other coatings. Dark-toned soils observed on disturbed surfaces may be derived from rocks and have derived mineralogy (+/-5 to 10%) of 45% pyroxene (20% Ca-rich pyroxene and 25% pigeonite), 40% sodic to intermediate plagioclase, and 15% olivine (forsterite 45% +/-5 to 10). Two spectrally distinct coatings are observed on rocks, a possible indicator of the interaction of water, rock, and airfall dust. Diurnal temperature data indicate particle sizes from 40 to 80 microm in hollows to approximately 0.5 to 3 mm in soils.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Christensen, P R -- Ruff, S W -- Fergason, R L -- Knudson, A T -- Anwar, S -- Arvidson, R E -- Bandfield, J L -- Blaney, D L -- Budney, C -- Calvin, W M -- Glotch, T D -- Golombek, M P -- Gorelick, N -- Graff, T G -- Hamilton, V E -- Hayes, A -- Johnson, J R -- McSween, H Y Jr -- Mehall, G L -- Mehall, L K -- Moersch, J E -- Morris, R V -- Rogers, A D -- Smith, M D -- Squyres, S W -- Wolff, M J -- Wyatt, M B -- New York, N.Y. -- Science. 2004 Aug 6;305(5685):837-42.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Geological Sciences, Arizona State University, Tempe, AZ 85287, USA. phil.christensen@asu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15297667" target="_blank"〉PubMed〈/a〉
    Keywords: Carbonates ; Geologic Sediments ; Interferometry ; Iron Compounds ; Magnesium Compounds ; *Mars ; *Minerals ; Oxides ; Silicates ; Spectrum Analysis ; Temperature ; Water
    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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  • 6
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    Inactivation of TNF signaling by rationally designed dominant-negative TNF variants (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-09-27
    Description: Tumor necrosis factor (TNF) is a key regulator of inflammatory responses and has been implicated in many pathological conditions. We used structure-based design to engineer variant TNF proteins that rapidly form heterotrimers with native TNF to give complexes that neither bind to nor stimulate signaling through TNF receptors. Thus, TNF is inactivated by sequestration. Dominant-negative TNFs represent a possible approach to anti-inflammatory biotherapeutics, and experiments in animal models show that the strategy can attenuate TNF-mediated pathology. Similar rational design could be used to engineer inhibitors of additional TNF superfamily cytokines as well as other multimeric ligands.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Steed, Paul M -- Tansey, Malu G -- Zalevsky, Jonathan -- Zhukovsky, Eugene A -- Desjarlais, John R -- Szymkowski, David E -- Abbott, Christina -- Carmichael, David -- Chan, Cheryl -- Cherry, Lisa -- Cheung, Peter -- Chirino, Arthur J -- Chung, Hyo H -- Doberstein, Stephen K -- Eivazi, Araz -- Filikov, Anton V -- Gao, Sarah X -- Hubert, Rene S -- Hwang, Marian -- Hyun, Linus -- Kashi, Sandhya -- Kim, Alice -- Kim, Esther -- Kung, James -- Martinez, Sabrina P -- Muchhal, Umesh S -- Nguyen, Duc-Hanh T -- O'Brien, Christopher -- O'Keefe, Donald -- Singer, Karen -- Vafa, Omid -- Vielmetter, Jost -- Yoder, Sean C -- Dahiyat, Bassil I -- New York, N.Y. -- Science. 2003 Sep 26;301(5641):1895-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Xencor, 111 West Lemon Avenue, Monrovia, CA 91016, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14512626" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Substitution ; Animals ; Antigens, CD/metabolism ; Apoptosis ; Arthritis, Experimental/drug therapy ; Biopolymers ; Caspases/metabolism ; Cell Line ; Cell Nucleus/metabolism ; Computer Simulation ; Disease Progression ; Enzyme-Linked Immunosorbent Assay ; Female ; Galactosamine/pharmacology ; HeLa Cells ; Humans ; Liver/drug effects ; NF-kappa B/metabolism ; Point Mutation ; *Protein Engineering ; Rats ; Receptors, Tumor Necrosis Factor/metabolism ; Receptors, Tumor Necrosis Factor, Type I ; Receptors, Tumor Necrosis Factor, Type II ; *Signal Transduction ; Transcription Factor RelA ; Transcription, Genetic ; Tumor Necrosis Factor-alpha/*antagonists & ; inhibitors/genetics/metabolism/*pharmacology
    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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  • 7
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    The influence of the proinflammatory cytokine, osteopontin, on autoimmune demyelinating disease (2001)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2001-11-27
    Description: Multiple sclerosis is a demyelinating disease, characterized by inflammation in the brain and spinal cord, possibly due to autoimmunity. Large-scale sequencing of cDNA libraries, derived from plaques dissected from brains of patients with multiple sclerosis (MS), indicated an abundance of transcripts for osteopontin (OPN). Microarray analysis of spinal cords from rats paralyzed by experimental autoimmune encephalomyelitis (EAE), a model of MS, also revealed increased OPN transcripts. Osteopontin-deficient mice were resistant to progressive EAE and had frequent remissions, and myelin-reactive T cells in OPN-/- mice produced more interleukin 10 and less interferon-gamma than in OPN+/+ mice. Osteopontin thus appears to regulate T helper cell-1 (TH1)-mediated demyelinating disease, and it may offer a potential target in blocking development of progressive MS.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chabas, D -- Baranzini, S E -- Mitchell, D -- Bernard, C C -- Rittling, S R -- Denhardt, D T -- Sobel, R A -- Lock, C -- Karpuj, M -- Pedotti, R -- Heller, R -- Oksenberg, J R -- Steinman, L -- New York, N.Y. -- Science. 2001 Nov 23;294(5547):1731-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, B002, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11721059" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Encephalomyelitis, Autoimmune, ; Experimental/genetics/immunology/metabolism/pathology ; Expressed Sequence Tags ; Gene Deletion ; *Gene Expression Profiling ; Gene Library ; Humans ; Inflammation/genetics/immunology/metabolism/pathology ; Interferon-gamma/genetics/metabolism ; Interleukin-10/genetics/metabolism ; Lymphocyte Activation ; Mice ; Mice, Knockout ; Multiple Sclerosis/*genetics/immunology/*metabolism/pathology ; Oligonucleotide Array Sequence Analysis ; Osteopontin ; RNA, Messenger/genetics/metabolism ; Rats ; Sialoglycoproteins/deficiency/genetics/*metabolism ; Spinal Cord/metabolism ; Th1 Cells/immunology
    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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  • 8
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    Paleobotanical evidence for near present-day levels of atmospheric Co2 during part of the tertiary (2001)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2001-06-26
    Description: Understanding the link between the greenhouse gas carbon dioxide (CO(2)) and Earth's temperature underpins much of paleoclimatology and our predictions of future global warming. Here, we use the inverse relationship between leaf stomatal indices and the partial pressure of CO(2) in modern Ginkgo biloba and Metasequoia glyptostroboides to develop a CO(2) reconstruction based on fossil Ginkgo and Metasequoia cuticles for the middle Paleocene to early Eocene and middle Miocene. Our reconstruction indicates that CO(2) remained between 300 and 450 parts per million by volume for these intervals with the exception of a single high estimate near the Paleocene/Eocene boundary. These results suggest that factors in addition to CO(2) are required to explain these past intervals of global warmth.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Royer, D L -- Wing, S L -- Beerling, D J -- Jolley, D W -- Koch, P L -- Hickey, L J -- Berner, R A -- New York, N.Y. -- Science. 2001 Jun 22;292(5525):2310-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Geology and Geophysics, Yale University, Post Office Box 208109, New Haven, CT 06520-8109, USA. dana.royer@yale.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11423657" target="_blank"〉PubMed〈/a〉
    Keywords: *Atmosphere ; *Carbon Dioxide ; Climate ; *Fossils ; Ginkgo biloba ; Gymnosperms/*cytology ; Partial Pressure ; Plant Leaves/cytology ; Plants, Medicinal ; Temperature ; Time
    Print ISSN: 0036-8075
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  • 9
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    Identification of ubiquitin ligases required for skeletal muscle atrophy (2001)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2001-10-27
    Description: Skeletal muscle adapts to decreases in activity and load by undergoing atrophy. To identify candidate molecular mediators of muscle atrophy, we performed transcript profiling. Although many genes were up-regulated in a single rat model of atrophy, only a small subset was universal in all atrophy models. Two of these genes encode ubiquitin ligases: Muscle RING Finger 1 (MuRF1), and a gene we designate Muscle Atrophy F-box (MAFbx), the latter being a member of the SCF family of E3 ubiquitin ligases. Overexpression of MAFbx in myotubes produced atrophy, whereas mice deficient in either MAFbx or MuRF1 were found to be resistant to atrophy. These proteins are potential drug targets for the treatment of muscle atrophy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bodine, S C -- Latres, E -- Baumhueter, S -- Lai, V K -- Nunez, L -- Clarke, B A -- Poueymirou, W T -- Panaro, F J -- Na, E -- Dharmarajan, K -- Pan, Z Q -- Valenzuela, D M -- DeChiara, T M -- Stitt, T N -- Yancopoulos, G D -- Glass, D J -- New York, N.Y. -- Science. 2001 Nov 23;294(5547):1704-8. Epub 2001 Oct 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY, 10591-6707, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11679633" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cloning, Molecular ; Creatine Kinase/genetics ; Creatine Kinase, MM Form ; *DNA-Binding Proteins ; Gene Deletion ; *Gene Expression Profiling ; Hindlimb Suspension ; Humans ; Immobilization ; Isoenzymes/genetics ; Mice ; Mice, Knockout ; Molecular Sequence Data ; Muscle Denervation ; Muscle Proteins/genetics ; Muscle, Skeletal/growth & development/*metabolism/pathology/physiopathology ; Muscular Atrophy/*genetics/pathology/physiopathology ; MyoD Protein/genetics ; Myogenic Regulatory Factor 5 ; Myogenin/genetics ; Peptide Synthases/chemistry/deficiency/genetics/*metabolism ; Phenotype ; Protein Binding ; RNA, Messenger/analysis/genetics ; Rats ; Rats, Sprague-Dawley ; SKP Cullin F-Box Protein Ligases ; *Trans-Activators ; Up-Regulation
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  • 10
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    Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch (2002)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2002-02-02
    Description: The hypoxia-inducible factors (HIFs) 1alpha and 2alpha are key mammalian transcription factors that exhibit dramatic increases in both protein stability and intrinsic transcriptional potency during low-oxygen stress. This increased stability is due to the absence of proline hydroxylation, which in normoxia promotes binding of HIF to the von Hippel-Lindau (VHL tumor suppressor) ubiquitin ligase. We now show that hypoxic induction of the COOH-terminal transactivation domain (CAD) of HIF occurs through abrogation of hydroxylation of a conserved asparagine in the CAD. Inhibitors of Fe(II)- and 2-oxoglutarate-dependent dioxygenases prevented hydroxylation of the Asn, thus allowing the CAD to interact with the p300 transcription coactivator. Replacement of the conserved Asn by Ala resulted in constitutive p300 interaction and strong transcriptional activity. Full induction of HIF-1alpha and -2alpha, therefore, relies on the abrogation of both Pro and Asn hydroxylation, which during normoxia occur at the degradation and COOH-terminal transactivation domains, respectively.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lando, David -- Peet, Daniel J -- Whelan, Dean A -- Gorman, Jeffrey J -- Whitelaw, Murray L -- New York, N.Y. -- Science. 2002 Feb 1;295(5556):858-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biosciences (Biochemistry), Adelaide University, SA 5005, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11823643" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Asparagine/*metabolism ; Basic Helix-Loop-Helix Transcription Factors ; Cell Hypoxia/*physiology ; Cell Line ; Humans ; Hydroxylation ; Hypoxia-Inducible Factor 1, alpha Subunit ; Mass Spectrometry ; Mice ; Mixed Function Oxygenases/metabolism ; Molecular Sequence Data ; Mutation ; Oxygen/*physiology ; Proline/metabolism ; Protein Structure, Tertiary ; Recombinant Fusion Proteins/metabolism ; Trans-Activators/chemistry/genetics/*metabolism ; Transcription Factors/chemistry/genetics/*metabolism ; *Transcriptional Activation
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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