| Polybromo-associated BRG1-associated factor components BRD7 and BAF180 are critical regulators of p53 required for induction of replicative senescence. | |
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MedLine Citation:
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PMID: 20660729 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A variety of tumor-suppressor mechanisms exist to promote genome integrity and organismal survival. One such mechanism is cellular senescence. In response to replicative aging, DNA damage, and oncogenic stimuli, the p53 and Rb pathways are activated to prevent the proliferation of damaged cells by inducing senescence or apoptosis. We have performed a loss-of-function genetic screen in primary human cells to identify components of the senescence machinery. Here we describe BRD7 and BAF180 as unique regulators of replicative senescence in human cells. Both regulate p53 transcriptional activity toward a subset of its target genes required for replicative and oncogenic stress senescence induction, and BRD7 physically interacts with p53. BRD7 is a deletion target in human cancer, suggesting that loss of BRD7 may provide an additional mechanism to antagonize p53 function in cancer cells. |
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Authors:
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Anna E Burrows; Agata Smogorzewska; Stephen J Elledge |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2010-07-26 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 107 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-08-11 Completed Date: 2010-09-07 Revised Date: 2011-07-25 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 14280-5 Citation Subset: IM |
Affiliation:
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The Howard Hughes Medical Institute and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. |
| Data Bank Information | |
Bank Name/Acc. No.:
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GEO/GSE22607 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Cell Aging* Cells, Cultured Chromosomal Proteins, Non-Histone / metabolism, physiology* DNA Helicases / metabolism* Humans Neoplasms / etiology*, genetics Nuclear Proteins / metabolism*, physiology* Protein Binding Transcription Factors / metabolism*, physiology* Tumor Suppressor Protein p53 / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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T32CA09216/CA/NCI NIH HHS; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
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0/BRD7 protein, human; 0/Chromosomal Proteins, Non-Histone; 0/Nuclear Proteins; 0/PBRM1 protein, human; 0/Transcription Factors; 0/Tumor Suppressor Protein p53; EC 3.6.1.-/DNA Helicases; EC 3.6.1.-/SMARCA4 protein, human |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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