Document Detail


p300 is required for orderly G1/S transition in human cancer cells.
MedLine Citation:
PMID:  16878158     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The role of the transcriptional coactivator p300 in cell cycle control has not been analysed in detail due to the lack of appropriate experimental systems. We have now examined cell cycle progression of p300-deficient cancer cell lines, where p300 was disrupted either by gene targeting (p300(-) cells) or knocked down using RNAi. Despite significant proliferation defects under normal growth conditions, p300-deficient cells progressed rapidly through G1 with premature S-phase entry. Accelerated G1/S transition was associated with early retinoblastoma (RB) hyperphosphorylation and activation of E2F targets. The p300-acetylase activity was dispensable since expression of a HAT-deficient p300 mutant reversed these changes. Co-immunoprecipitation showed p300/RB interaction occurs in vivo during G1, and this interaction has two peaks: in early G1 with unphosphorylated RB and in late G1 with phosphorylated RB. In vitro kinase assays showed that p300 directly inhibits cdk6-mediated RB phosphorylation, suggesting p300 acts in early G1 to prevent RB hyperphosphorylation and delay premature S-phase entry. Paradoxically, continued cycling of p300(-) cells despite prolonged serum depletion was observed, and this occurred in association with persistent RB hyperphosphorylation. Altogether, these results suggest that p300 has an important role in G1/S control, possibly by modulating RB phosphorylation.
Authors:
N G Iyer; J Xian; S-F Chin; A J Bannister; Y Daigo; S Aparicio; T Kouzarides; C Caldas
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-07-31
Journal Detail:
Title:  Oncogene     Volume:  26     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2007-01-04     Completed Date:  2007-02-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  21-9     Citation Subset:  IM    
Affiliation:
Cancer Genomics Program, Department of Oncology, University of Cambridge, Hutchison/MRC Research Centre, Cambridge, UK.
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MeSH Terms
Descriptor/Qualifier:
Base Sequence
Cell Division
DNA Primers
G1 Phase*
Humans
Neoplasms / pathology*
Phosphorylation
Retinoblastoma Protein / metabolism
S Phase*
Tumor Cells, Cultured
p300-CBP Transcription Factors / physiology*
Chemical
Reg. No./Substance:
0/DNA Primers; 0/Retinoblastoma Protein; EC 2.3.1.48/p300-CBP Transcription Factors

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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