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  • Astronomy  (109)
  • Mutation  (94)
  • 2000-2004  (203)
  • 1980-1984
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  • 2001  (89)
  • 1
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    Sequence interpretation. Functional annotation of mouse genome sequences (2001)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2001-03-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nadeau, J H -- Balling, R -- Barsh, G -- Beier, D -- Brown, S D -- Bucan, M -- Camper, S -- Carlson, G -- Copeland, N -- Eppig, J -- Fletcher, C -- Frankel, W N -- Ganten, D -- Goldowitz, D -- Goodnow, C -- Guenet, J L -- Hicks, G -- Hrabe de Angelis, M -- Jackson, I -- Jacob, H J -- Jenkins, N -- Johnson, D -- Justice, M -- Kay, S -- Kingsley, D -- Lehrach, H -- Magnuson, T -- Meisler, M -- Poustka, A -- Rinchik, E M -- Rossant, J -- Russell, L B -- Schimenti, J -- Shiroishi, T -- Skarnes, W C -- Soriano, P -- Stanford, W -- Takahashi, J S -- Wurst, W -- Zimmer, A -- International Mouse Mutagenesis Consortium -- New York, N.Y. -- Science. 2001 Feb 16;291(5507):1251-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, BRB 624, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA. jhn4@po.cwru.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11233449" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chromosome Mapping ; *Computational Biology ; Costs and Cost Analysis ; Genes/physiology ; Genetic Techniques ; *Genome ; *Genomics ; International Cooperation ; Mice/*genetics ; Mutagenesis ; Mutation ; Phenotype ; Private Sector ; Public Sector ; Research Support as Topic ; *Sequence Analysis, DNA
    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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    Chromosomal effects of rapid gene evolution in Drosophila melanogaster (2001)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2001-01-06
    Description: Rapid adaptive fixation of a new favorable mutation is expected to affect neighboring genes along the chromosome. Evolutionary theory predicts that the chromosomal region would show a reduced level of genetic variation and an excess of rare alleles. We have confirmed these predictions in a region of the X chromosome of Drosophila melanogaster that contains a newly evolved gene for a component of the sperm axoneme. In D. simulans, where the novel gene does not exist, the pattern of genetic variation is consistent with selection against recurrent deleterious mutations. These findings imply that the pattern of genetic variation along a chromosome may be useful for inferring its evolutionary history and for revealing regions in which recent adaptive fixations have taken place.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nurminsky, D -- Aguiar, D D -- Bustamante, C D -- Hartl, D L -- GM 60035/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2001 Jan 5;291(5501):128-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Anatomy and Cell Biology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11141564" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Axonemal Dyneins ; Drosophila/genetics ; *Drosophila Proteins ; Drosophila melanogaster/*genetics ; Dyneins/*genetics ; *Evolution, Molecular ; *Genes, Insect ; *Genetic Variation ; Likelihood Functions ; Logistic Models ; Mutation ; Polymorphism, Genetic ; Selection, Genetic ; X Chromosome/*genetics
    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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    Mutations in a human ROBO gene disrupt hindbrain axon pathway crossing and morphogenesis (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-04-24
    Description: The mechanisms controlling axon guidance are of fundamental importance in understanding brain development. Growing corticospinal and somatosensory axons cross the midline in the medulla to reach their targets and thus form the basis of contralateral motor control and sensory input. The motor and sensory projections appeared uncrossed in patients with horizontal gaze palsy with progressive scoliosis (HGPPS). In patients affected with HGPPS, we identified mutations in the ROBO3 gene, which shares homology with roundabout genes important in axon guidance in developing Drosophila, zebrafish, and mouse. Like its murine homolog Rig1/Robo3, but unlike other Robo proteins, ROBO3 is required for hindbrain axon midline crossing.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1618874/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1618874/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jen, Joanna C -- Chan, Wai-Man -- Bosley, Thomas M -- Wan, Jijun -- Carr, Janai R -- Rub, Udo -- Shattuck, David -- Salamon, Georges -- Kudo, Lili C -- Ou, Jing -- Lin, Doris D M -- Salih, Mustafa A M -- Kansu, Tulay -- Al Dhalaan, Hesham -- Al Zayed, Zayed -- MacDonald, David B -- Stigsby, Bent -- Plaitakis, Andreas -- Dretakis, Emmanuel K -- Gottlob, Irene -- Pieh, Christina -- Traboulsi, Elias I -- Wang, Qing -- Wang, Lejin -- Andrews, Caroline -- Yamada, Koki -- Demer, Joseph L -- Karim, Shaheen -- Alger, Jeffry R -- Geschwind, Daniel H -- Deller, Thomas -- Sicotte, Nancy L -- Nelson, Stanley F -- Baloh, Robert W -- Engle, Elizabeth C -- DC00162/DC/NIDCD NIH HHS/ -- DC05524/DC/NIDCD NIH HHS/ -- EY12498/EY/NEI NIH HHS/ -- EY13583/EY/NEI NIH HHS/ -- EY15298/EY/NEI NIH HHS/ -- EY15311/EY/NEI NIH HHS/ -- MH60233/MH/NIMH NIH HHS/ -- P30 HD 18655/HD/NICHD NIH HHS/ -- R01 EY008313/EY/NEI NIH HHS/ -- R01 EY008313-14/EY/NEI NIH HHS/ -- R01 HL066251/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2004 Jun 4;304(5676):1509-13. Epub 2004 Apr 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, University of California, Los Angeles, CA 90095, USA. jjen@ucla.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15105459" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Alternative Splicing ; Amino Acid Motifs ; Amino Acid Sequence ; Axons/*physiology ; Evoked Potentials, Motor ; Evoked Potentials, Somatosensory ; Female ; Functional Laterality ; Genetic Linkage ; Humans ; In Situ Hybridization ; Magnetic Resonance Imaging ; Male ; Medulla Oblongata/growth & development/pathology ; Microsatellite Repeats ; Molecular Sequence Data ; Morphogenesis ; Mutation ; Neural Pathways ; Ophthalmoplegia/*genetics/pathology/physiopathology ; Pedigree ; Protein Structure, Tertiary ; Receptors, Immunologic/chemistry/*genetics/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Rhombencephalon/*growth & development/pathology ; Scoliosis/*genetics/pathology/physiopathology ; Sequence Analysis, DNA ; Syndrome
    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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    Integrase inhibitors and cellular immunity suppress retroviral replication in rhesus macaques (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-07-13
    Description: We describe the efficacy of L-870812, an inhibitor of HIV-1 and SIV integrase, in rhesus macaques infected with the simian-human immunodeficiency virus (SHIV) 89.6P. When initiated before CD4 cell depletion, L-870812 therapy mediated a sustained suppression of viremia, preserving CD4 levels and permitting the induction of virus-specific cellular immunity. L-870812 was also active in chronic infection; however, the magnitude and durability of the effect varied in conjunction with the pretreatment immune response and viral load. These studies demonstrate integrase inhibitor activity in vivo and suggest that cellular immunity facilitates chemotherapeutic efficacy in retroviral infections.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hazuda, Daria J -- Young, Steven D -- Guare, James P -- Anthony, Neville J -- Gomez, Robert P -- Wai, John S -- Vacca, Joseph P -- Handt, Larry -- Motzel, Sherri L -- Klein, Hilton J -- Dornadula, Geethanjali -- Danovich, Robert M -- Witmer, Marc V -- Wilson, Keith A A -- Tussey, Lynda -- Schleif, William A -- Gabryelski, Lori S -- Jin, Lixia -- Miller, Michael D -- Casimiro, Danilo R -- Emini, Emilio A -- Shiver, John W -- New York, N.Y. -- Science. 2004 Jul 23;305(5683):528-32. Epub 2004 Jul 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry, Merck Research Laboratories, Post Office Box 4, West Point, PA 19486, USA. daria_hazuda@merck.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15247437" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/*drug therapy/*immunology/virology ; Animals ; Anti-HIV Agents/administration & dosage/blood/pharmacology/therapeutic use ; CD4 Lymphocyte Count ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Cells, Cultured ; Drug Resistance, Viral ; HIV Integrase/genetics/metabolism ; HIV Integrase Inhibitors/administration & dosage/blood/pharmacology/therapeutic ; use ; HIV-1/drug effects/enzymology/genetics/*physiology ; Immunity, Cellular ; Integrase Inhibitors/administration & dosage/blood/pharmacology/*therapeutic use ; Integrases/genetics/metabolism ; Leukocytes, Mononuclear/virology ; Macaca mulatta ; Mutation ; Naphthyridines/administration & dosage/blood/pharmacology/*therapeutic use ; Simian Acquired Immunodeficiency Syndrome/*drug therapy/*immunology/virology ; Simian Immunodeficiency Virus/drug effects/enzymology/genetics/*physiology ; Viral Load ; Viremia/drug therapy ; Virus Replication/drug effects
    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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  • 5
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    Spitzer 24 Micron Observations of Optical/Near-Infrared-Selected Extremely Red Galaxies: Evidence for Assembly of Massive Galaxies at Z approximately equal to 1-2? (2004)
    In:  Other Sources
    Details
    Publication Date: 2019-07-13
    Description: We carried out direct measurement of the fraction of dusty sources in a sample of extremely red galaxies with (R - Ks) 〉= 5.3 mag and Ks 〈 20:2 mag, using 24 micron data from the Spitzer Space Telescope. Combining deep 24 micron Ks- and R-band data over an area of ~64 arcmin(sup 2) in ELAIS N1 of the Spitzer First Look Survey (FLS), we find that 50% +/- 6% of our extremely red object (ERO) sample have measurable 24 micron flux above the 3 (sigma) flux limit of 40 (micro)Jy. This flux limit corresponds to a star formation rate (SFR) of 12 solar masses per year ~1, much more sensitive than any previous long-wavelength measurement. The 24 micron-detected EROs have 24 micron/2.2 micron and 24 micron/0.7 micron flux ratios consistent with infrared luminous, dusty sources at z 〉= 1, and are an order of magnitude too red to be explained by an infrared quiescent spiral or a pure old stellar population at any redshift. Some of these 24 micron-detected EROs could be active galactic nuclei; however, the fraction among the whole ERO sample is probably small, 10%-20%, as suggested by deep X-ray observations as well as optical spectroscopy. Keck optical spectroscopy of a sample of similarly selected EROs in the FLS field suggests that most of the EROs in ELAIS N1 are probably at z ~1. The mean 24 micron flux (167 (micro)Jy) of the 24 micron-detected ERO sample roughly corresponds to the rest-frame 12 micron luminosity, (nu)L(nu)(12 micron, of 3x10(exp 10)(deg) solar luminosities at z ~1. Using the c IRAS (nu)L(nu)(12 (micron) and infrared luminosity LIR(8-1000 (micron), we infer that the (LIR) of the 24 micron- detected EROs is 3 x 10(exp 11) and 1 x 10(exp 12) solar luminosities at z = 1.0 and similar to that of local luminous infrared galaxies (LIRGs) and ultraluminous infrared galaxies (ULIRGs). The corresponding SFR would be roughly 50-170 solar masses per year. If the timescale of this starbursting phase is on the order of 108 yr as inferred for the local LIRGs and ULIRGs, the lower limit on the masses of these 24 micron-detected EROs is 5 x 10(exp 9) to 2 x 10(exp 10) solar masses. It is plausible that some of the starburst EROs are in the midst of a violent transformation to become massive early type galaxies at the epoch of z ~1-2.
    Keywords: Astronomy
    Type: The Astrophysical Journal Supplement Series; 154; 75-79
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  • 6
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    Spitzer 24micron Observations of Optical/Near-IR Selected Extremely Red Galaxies: Evidence for Assembly of Massive Galaxies at z approximately 1 - 2? (2004)
    In:  Other Sources
    Details
    Publication Date: 2019-07-13
    Description: We carried out the direct measurement of the fraction of dusty sources in a sample of extremely red galaxies with (R-K(sub s)) greater than or equal to 5.3 mag and K(sub s) less than 20.2 mag, using from the Spitzer Space Telescope. Combining deep 24 micrometers, K(sub s)- and R-band data over an area of approximately 64 sq.arcmin in the ELAIS N1 field of the Spitzer First Look Survey (FLS), we find that 50 +/- 60% of our ERO sample have measurable 24 micrometer flux above the 3(sigma) flux limit of 40 microns Jy. This flux limit corresponds to a SFR of 12 solar mass/yr at z approximately 1, much mo previous long wavelength measurement. The 24fJ,m-detected EROs have 24-to2.2 and 24-to-0.7micrometr flux ratios consistent with infrared luminous, dusty sources at z approx. 1, and an order of magnitude too red to be explained by an infrared quiescent spiral or a pure old stellar population at any redshift. Some of these 24 micrometer-detected EROs could be AGN, however, the fraction among the whole ERO sample is probably small, 10-20%, as suggested by deep X-ray observations as well as optical spectroscopy. Keck optical spectroscopy of a sample of similarly selected EROs in the FLS field suggests that most of the EROs in ELAIS Nl are probably at z approx. 1.
    Keywords: Astronomy
    Type: Space Telescope Science Institute (STSCI) Mini Workshop Massive Galaxies over Cosmic Time; Sep 27, 2004 - Sep 29, 2004; Baltimore, MD; United States
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    NASA TECHNICAL REPORTS
  • 7
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    Two-state allosteric behavior in a single-domain signaling protein (2001)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2001-03-27
    Description: Protein actions are usually discussed in terms of static structures, but function requires motion. We find a strong correlation between phosphorylation-driven activation of the signaling protein NtrC and microsecond time-scale backbone dynamics. Using nuclear magnetic resonance relaxation, we characterized the motions of NtrC in three functional states: unphosphorylated (inactive), phosphorylated (active), and a partially active mutant. These dynamics are indicative of exchange between inactive and active conformations. Both states are populated in unphosphorylated NtrC, and phosphorylation shifts the equilibrium toward the active species. These results support a dynamic population shift between two preexisting conformations as the underlying mechanism of activation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Volkman, B F -- Lipson, D -- Wemmer, D E -- Kern, D -- GM62117/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2001 Mar 23;291(5512):2429-33.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Magnetic Resonance Facility at Madison (NMRFAM), Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11264542" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; *Bacterial Proteins ; Binding Sites ; DNA-Binding Proteins/*chemistry/genetics/*metabolism ; Models, Molecular ; Motion ; Mutation ; Nuclear Magnetic Resonance, Biomolecular ; PII Nitrogen Regulatory Proteins ; Phosphorylation ; *Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Signal Transduction ; Time ; *Trans-Activators ; *Transcription Factors
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
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  • 8
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    Methylation of histone H4 at arginine 3 facilitating transcriptional activation by nuclear hormone receptor (2001)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2001-06-02
    Description: Acetylation of core histone tails plays a fundamental role in transcription regulation. In addition to acetylation, other posttranslational modifications, such as phosphorylation and methylation, occur in core histone tails. Here, we report the purification, molecular identification, and functional characterization of a histone H4-specific methyltransferase PRMT1, a protein arginine methyltransferase. PRMT1 specifically methylates arginine 3 (Arg 3) of H4 in vitro and in vivo. Methylation of Arg 3 by PRMT1 facilitates subsequent acetylation of H4 tails by p300. However, acetylation of H4 inhibits its methylation by PRMT1. Most important, a mutation in the S-adenosyl-l-methionine-binding site of PRMT1 substantially crippled its nuclear receptor coactivator activity. Our finding reveals Arg 3 of H4 as a novel methylation site by PRMT1 and indicates that Arg 3 methylation plays an important role in transcriptional regulation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, H -- Huang, Z Q -- Xia, L -- Feng, Q -- Erdjument-Bromage, H -- Strahl, B D -- Briggs, S D -- Allis, C D -- Wong, J -- Tempst, P -- Zhang, Y -- GM63067-01/GM/NIGMS NIH HHS/ -- P30 CA08748/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2001 Aug 3;293(5531):853-7. Epub 2001 May 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11387442" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Amino Acid Sequence ; Animals ; Arginine/*metabolism ; Binding Sites ; Cell Nucleus/metabolism ; HeLa Cells ; Histones/chemistry/*metabolism ; Humans ; Hydroxamic Acids/pharmacology ; Intracellular Signaling Peptides and Proteins ; Lysine/metabolism ; Methylation ; Methyltransferases/chemistry/genetics/isolation & purification/*metabolism ; Molecular Sequence Data ; Mutation ; Oocytes ; Protein-Arginine N-Methyltransferases ; Receptors, Androgen/*metabolism ; Recombinant Proteins/metabolism ; S-Adenosylmethionine/metabolism ; *Transcriptional Activation ; Xenopus
    Print ISSN: 0036-8075
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  • 9
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    A process for controlling intracellular bacterial infections induced by membrane injury (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-06-05
    Description: Strategies for inhibiting phagolysosome fusion are essential for the intracellular survival and replication of many pathogens. We found that the lysosomal synaptotagmin Syt VII is required for a mechanism that promotes phagolysosomal fusion and limits the intracellular growth of pathogenic bacteria. Syt VII was required for a form of Ca2+-dependent phagolysosome fusion that is analogous to Ca2+-regulated exocytosis of lysosomes, which can be triggered by membrane injury. Bacterial type III secretion systems, which permeabilize membranes and cause Ca2+ influx in mammalian cells, promote lysosomal exocytosis and inhibit intracellular survival in Syt VII +/+ but not -/- cells. Thus, the lysosomal repair response can also protect cells against pathogens that trigger membrane permeabilization.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roy, Deepannita -- Liston, David R -- Idone, Vincent J -- Di, Anke -- Nelson, Deborah J -- Pujol, Celine -- Bliska, James B -- Chakrabarti, Sabyasachi -- Andrews, Norma W -- AI34867/AI/NIAID NIH HHS/ -- AI43389/AI/NIAID NIH HHS/ -- AI48507/AI/NIAID NIH HHS/ -- GM64625/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2004 Jun 4;304(5676):1515-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Microbial Pathogenesis and Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15178804" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacteria/*growth & development/metabolism ; Bacterial Proteins/genetics/metabolism ; CHO Cells ; Calcium/metabolism ; *Calcium-Binding Proteins ; Cell Membrane/*physiology ; Cells, Cultured ; Cricetinae ; Endocytosis ; Exocytosis ; Listeria monocytogenes/growth & development ; Lysosomes/microbiology/physiology ; Macrophages/microbiology ; Membrane Glycoproteins/genetics/*physiology ; Mice ; Mutation ; Nerve Tissue Proteins/genetics/*physiology ; Permeability ; Phagosomes/microbiology/physiology ; Salmonella typhimurium/*growth & development/metabolism ; Synaptotagmins ; Vacuoles/microbiology ; Yersinia pseudotuberculosis/genetics/growth & development
    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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  • 10
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    Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-02-14
    Description: The tumor suppressor p53 exerts its anti-neoplastic activity primarily through the induction of apoptosis. We found that cytosolic localization of endogenous wild-type or trans-activation-deficient p53 was necessary and sufficient for apoptosis. p53 directly activated the proapoptotic Bcl-2 protein Bax in the absence of other proteins to permeabilize mitochondria and engage the apoptotic program. p53 also released both proapoptotic multidomain proteins and BH3-only proteins [Proapoptotic Bcl-2 family proteins that share only the third Bcl-2 homology domain (BH3)] that were sequestered by Bcl-xL. The transcription-independent activation of Bax by p53 occurred with similar kinetics and concentrations to those produced by activated Bid. We propose that when p53 accumulates in the cytosol, it can function analogously to the BH3-only subset of proapoptotic Bcl-2 proteins to activate Bax and trigger apoptosis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chipuk, Jerry E -- Kuwana, Tomomi -- Bouchier-Hayes, Lisa -- Droin, Nathalie M -- Newmeyer, Donald D -- Schuler, Martin -- Green, Douglas R -- AI40646/AI/NIAID NIH HHS/ -- AI47891/AI/NIAID NIH HHS/ -- GM52735/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2004 Feb 13;303(5660):1010-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14963330" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Apoptosis ; BH3 Interacting Domain Death Agonist Protein ; Carrier Proteins/metabolism ; Cell Line, Transformed ; Cell Nucleus/metabolism ; Cells, Cultured ; Cytochromes c/metabolism ; Cytosol/metabolism ; Gene Expression Regulation ; Genes, p53 ; HeLa Cells ; Humans ; Intracellular Membranes/*physiology ; Liposomes/metabolism ; Mice ; Mitochondria/*physiology ; Mutation ; Permeability ; Protein Conformation ; Proto-Oncogene Proteins/chemistry/genetics/*metabolism ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Recombinant Fusion Proteins/metabolism ; Tumor Suppressor Protein p53/chemistry/*metabolism ; Ultraviolet Rays ; Wheat Germ Agglutinins/pharmacology ; bcl-2-Associated X Protein ; bcl-X Protein
    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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