| p53 directly transactivates Δ133p53α, regulating cell fate outcome in response to DNA damage. | |
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MedLine Citation:
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PMID: 20689555 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We have previously reported that the human p53 gene encodes at least nine different p53 isoforms, including Δ133p53α, which can modulate p53 transcriptional activity and apoptosis. In this study, we aimed to investigate the regulation of Δ133p53α isoform expression and its physiological role in modulating cell cycle arrest and apoptosis. We report here that in response to a low dose of doxorubicin (which induces cell cycle arrest without promoting apoptosis), p53 directly transactivates the human p53 internal promoter, inducing Δ133p53α protein expression. The induced Δ133p53α then inhibits p53-dependent apoptosis and G1 arrest without inhibiting p53-dependent G2 arrest. Therefore, endogenous Δ133p53α does not exclusively function in a dominant-negative manner toward p53, but differentially regulates cell cycle arrest and apoptosis. |
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Authors:
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M Aoubala; F Murray-Zmijewski; M P Khoury; K Fernandes; S Perrier; H Bernard; A-C Prats; D P Lane; J-C Bourdon |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-06 |
Journal Detail:
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Title: Cell death and differentiation Volume: 18 ISSN: 1476-5403 ISO Abbreviation: Cell Death Differ. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-10 Completed Date: 2011-04-25 Revised Date: 2011-08-04 |
Medline Journal Info:
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Nlm Unique ID: 9437445 Medline TA: Cell Death Differ Country: England |
Other Details:
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Languages: eng Pagination: 248-58 Citation Subset: IM |
Affiliation:
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Centre for Oncology and Molecular Medicine, INSERM-European Associated Laboratory U858, University of Dundee, College of Medicine, Dundee, UK. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis Base Sequence Cell Line, Tumor DNA Damage* Doxorubicin / pharmacology G1 Phase Genes, p53 Humans Introns Molecular Sequence Data Promoter Regions, Genetic Protein Isoforms / chemistry, genetics, metabolism Transcriptional Activation* Tumor Suppressor Protein p53 / chemistry, genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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A6613//Cancer Research UK; //Cancer Research UK |
| Chemical | |
Reg. No./Substance:
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0/Protein Isoforms; 0/Tumor Suppressor Protein p53; 23214-92-8/Doxorubicin |
| Comments/Corrections | |
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