| E2f1-3 switch from activators in progenitor cells to repressors in differentiating cells. | |
| | |
MedLine Citation:
|
PMID: 20016602 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
In the established model of mammalian cell cycle control, the retinoblastoma protein (Rb) functions to restrict cells from entering S phase by binding and sequestering E2f activators (E2f1, E2f2 and E2f3), which are invariably portrayed as the ultimate effectors of a transcriptional program that commit cells to enter and progress through S phase. Using a panel of tissue-specific cre-transgenic mice and conditional E2f alleles we examined the effects of E2f1, E2f2 and E2f3 triple deficiency in murine embryonic stem cells, embryos and small intestines. We show that in normal dividing progenitor cells E2f1-3 function as transcriptional activators, but contrary to the current view, are dispensable for cell division and instead are necessary for cell survival. In differentiating cells E2f1-3 function in a complex with Rb as repressors to silence E2f targets and facilitate exit from the cell cycle. The inactivation of Rb in differentiating cells resulted in a switch of E2f1-3 from repressors to activators, leading to the superactivation of E2f responsive targets and ectopic cell divisions. Loss of E2f1-3 completely suppressed these phenotypes caused by Rb deficiency. This work contextualizes the activator versus repressor functions of E2f1-3 in vivo, revealing distinct roles in dividing versus differentiating cells and in normal versus cancer-like cell cycles. |
| | |
Authors:
|
Jean-Leon Chong; Pamela L Wenzel; M Teresa Sáenz-Robles; Vivek Nair; Antoney Ferrey; John P Hagan; Yorman M Gomez; Nidhi Sharma; Hui-Zi Chen; Madhu Ouseph; Shu-Huei Wang; Prashant Trikha; Brian Culp; Louise Mezache; Douglas J Winton; Owen J Sansom; Danian Chen; Rod Bremner; Paul G Cantalupo; Michael L Robinson; James M Pipas; Gustavo Leone |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
|
Title: Nature Volume: 462 ISSN: 1476-4687 ISO Abbreviation: Nature Publication Date: 2009 Dec |
Date Detail:
|
Created Date: 2009-12-17 Completed Date: 2010-02-01 Revised Date: 2011-09-26 |
Medline Journal Info:
|
Nlm Unique ID: 0410462 Medline TA: Nature Country: England |
Other Details:
|
Languages: eng Pagination: 930-4 Citation Subset: IM |
Affiliation:
|
Department of Molecular Virology, Immunology and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA. |
| Data Bank Information | |
Bank Name/Acc. No.:
|
GEO/GSE16454 |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Alleles Animals Apoptosis Cell Cycle / genetics, physiology Cell Differentiation* Cell Proliferation E2F Transcription Factors / deficiency, genetics, metabolism* E2F1 Transcription Factor / deficiency, genetics, metabolism E2F2 Transcription Factor / deficiency, genetics, metabolism E2F3 Transcription Factor / deficiency, genetics, metabolism Embryo, Mammalian / cytology, metabolism Embryonic Stem Cells / cytology*, metabolism* Female Gene Expression Regulation* Intestine, Small / cytology, metabolism Mice Mice, Transgenic Repressor Proteins / deficiency, genetics, metabolism* Retinoblastoma Protein / deficiency, metabolism |
| Grant Support | |
ID/Acronym/Agency:
|
5 T32 CA106196-04/CA/NCI NIH HHS; CA098956/CA/NCI NIH HHS; P01CA097189/CA/NCI NIH HHS; R01 CA098956-06A2/CA/NCI NIH HHS; R01CA82259/CA/NCI NIH HHS; R01CA85619/CA/NCI NIH HHS; R01HD04470/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/E2F Transcription Factors; 0/E2F1 Transcription Factor; 0/E2F2 Transcription Factor; 0/E2F3 Transcription Factor; 0/E2f1 protein, mouse; 0/E2f2 protein, mouse; 0/E2f3 protein, mouse; 0/Repressor Proteins; 0/Retinoblastoma Protein |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Division and apoptosis of E2f-deficient retinal progenitors.
Next Document: Mammalian SUMO E3-ligases PIAS1 and PIAS4 promote responses to DNA double-strand breaks.