Document Detail


A bistable Rb-E2F switch underlies the restriction point.
MedLine Citation:
PMID:  18364697     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The restriction point (R-point) marks the critical event when a mammalian cell commits to proliferation and becomes independent of growth stimulation. It is fundamental for normal differentiation and tissue homeostasis, and seems to be dysregulated in virtually all cancers. Although the R-point has been linked to various activities involved in the regulation of G1-S transition of the mammalian cell cycle, the underlying mechanism remains unclear. Using single-cell measurements, we show here that the Rb-E2F pathway functions as a bistable switch to convert graded serum inputs into all-or-none E2F responses. Once turned ON by sufficient serum stimulation, E2F can memorize and maintain this ON state independently of continuous serum stimulation. We further show that, at critical concentrations and duration of serum stimulation, bistable E2F activation correlates directly with the ability of a cell to traverse the R-point.
Authors:
Guang Yao; Tae Jun Lee; Seiichi Mori; Joseph R Nevins; Lingchong You
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Publication Detail:
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:  2008-03-23
Journal Detail:
Title:  Nature cell biology     Volume:  10     ISSN:  1476-4679     ISO Abbreviation:  Nat. Cell Biol.     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-04-01     Completed Date:  2008-05-12     Revised Date:  2008-05-21    
Medline Journal Info:
Nlm Unique ID:  100890575     Medline TA:  Nat Cell Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  476-82     Citation Subset:  IM    
Affiliation:
Institute for Genome Sciences and Policy, Duke University, Durham, NC 27708, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Cycle / physiology*
Cell Differentiation / physiology*
Cells, Cultured
Culture Media / chemistry
E2F Transcription Factors / genetics,  metabolism*
Gene Expression Regulation
Genes, Reporter
Homeostasis
Models, Theoretical
Rats
Recombinant Fusion Proteins / genetics,  metabolism
Retinoblastoma Protein / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
5-U24-CA112952-03/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Culture Media; 0/E2F Transcription Factors; 0/Recombinant Fusion Proteins; 0/Retinoblastoma Protein

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


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