| A G1 checkpoint mediated by the retinoblastoma protein that is dispensable in terminal differentiation but essential for senescence. | |
| | |
MedLine Citation:
|
PMID: 20008551 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Terminally differentiated cell types are needed to live and function in a postmitotic state for a lifetime. Cellular senescence is another type of permanent arrest that blocks the proliferation of cells in response to genotoxic stress. Here we show that the retinoblastoma protein (pRB) uses a mechanism to block DNA replication in senescence that is distinct from its role in permanent cell cycle exit associated with terminal differentiation. Our work demonstrates that a subtle mutation in pRB that cripples its ability to interact with chromatin regulators impairs heterochromatinization and repression of E2F-responsive promoters during senescence. In contrast, terminally differentiated nerve and muscle cells bearing the same mutation fully exit the cell cycle and block E2F-responsive gene expression by a different mechanism. Remarkably, this reveals that pRB recruits chromatin regulators primarily to engage a stress-responsive G(1) arrest program. |
| | |
Authors:
|
Srikanth Talluri; Christian E Isaac; Mohammad Ahmad; Shauna A Henley; Sarah M Francis; Alison L Martens; Rod Bremner; Frederick A Dick |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-12-14 |
Journal Detail:
|
Title: Molecular and cellular biology Volume: 30 ISSN: 1098-5549 ISO Abbreviation: Mol. Cell. Biol. Publication Date: 2010 Feb |
Date Detail:
|
Created Date: 2010-01-27 Completed Date: 2010-02-12 Revised Date: 2010-09-28 |
Medline Journal Info:
|
Nlm Unique ID: 8109087 Medline TA: Mol Cell Biol Country: United States |
Other Details:
|
Languages: eng Pagination: 948-60 Citation Subset: IM |
Affiliation:
|
Department of Biochemistry, University of Western Ontario, London, Ontario, Canada. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Cell Aging* Cell Differentiation* Cell Line DNA Replication E2F Transcription Factors / genetics, metabolism Fibroblasts / cytology, metabolism G1 Phase* Heterochromatin / metabolism Humans Mice Mice, Knockout Mutation Promoter Regions, Genetic Retinoblastoma Protein / deficiency, genetics, metabolism* Transcription, Genetic |
| Grant Support | |
ID/Acronym/Agency:
|
MOP-64243//Canadian Institutes of Health Research; MOP-64253//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
|
0/E2F Transcription Factors; 0/Heterochromatin; 0/Retinoblastoma Protein |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Rap1 in Candida albicans: an unusual structural organization and a critical function in suppressing ...
Next Document: The final step in 5.8S rRNA processing is cytoplasmic in Saccharomyces cerevisiae.