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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6862
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pubmed:dateCreated |
2001-11-23
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pubmed:abstractText |
The retinoblastoma tumour suppressor (Rb) pathway is believed to have a critical role in the control of cellular proliferation by regulating E2F activities. E2F1, E2F2 and E2F3 belong to a subclass of E2F factors thought to act as transcriptional activators important for progression through the G1/S transition. Here we show, by taking a conditional gene targeting approach, that the combined loss of these three E2F factors severely affects E2F target expression and completely abolishes the ability of mouse embryonic fibroblasts to enter S phase, progress through mitosis and proliferate. Loss of E2F function results in an elevation of p21Cip1 protein, leading to a decrease in cyclin-dependent kinase activity and Rb phosphorylation. These findings suggest a function for this subclass of E2F transcriptional activators in a positive feedback loop, through down-modulation of p21Cip1, that leads to the inactivation of Rb-dependent repression and S phase entry. By targeting the entire subclass of E2F transcriptional activators we provide direct genetic evidence for their essential role in cell cycle progression, proliferation and development.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cdkn1a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cre recombinase,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/E2F Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/E2F1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/E2F2 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/E2F3 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/E2f1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/E2f3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Integrases,
http://linkedlifedata.com/resource/pubmed/chemical/Retinoblastoma Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Viral Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0028-0836
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pubmed:author |
pubmed-author:ChongG TGT,
pubmed-author:FieldS JSJ,
pubmed-author:GiangrandePP,
pubmed-author:GreenbergM EME,
pubmed-author:LeoneGG,
pubmed-author:MaitiBB,
pubmed-author:NevinsJ RJR,
pubmed-author:NuckollsFF,
pubmed-author:OrkinSS,
pubmed-author:RobinsonM LML,
pubmed-author:SaavedraH IHI,
pubmed-author:SanoDD,
pubmed-author:TimmersCC,
pubmed-author:WrightF AFA,
pubmed-author:WuLL
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pubmed:issnType |
Print
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pubmed:day |
22
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pubmed:volume |
414
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
457-62
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:11719808-Animals,
pubmed-meshheading:11719808-Cell Cycle Proteins,
pubmed-meshheading:11719808-Cell Division,
pubmed-meshheading:11719808-Cell Line,
pubmed-meshheading:11719808-Cyclin-Dependent Kinase Inhibitor p21,
pubmed-meshheading:11719808-Cyclins,
pubmed-meshheading:11719808-DNA-Binding Proteins,
pubmed-meshheading:11719808-Down-Regulation,
pubmed-meshheading:11719808-E2F Transcription Factors,
pubmed-meshheading:11719808-E2F1 Transcription Factor,
pubmed-meshheading:11719808-E2F2 Transcription Factor,
pubmed-meshheading:11719808-E2F3 Transcription Factor,
pubmed-meshheading:11719808-Fibroblasts,
pubmed-meshheading:11719808-Gene Targeting,
pubmed-meshheading:11719808-Integrases,
pubmed-meshheading:11719808-Mice,
pubmed-meshheading:11719808-Mice, Inbred C57BL,
pubmed-meshheading:11719808-Mice, Knockout,
pubmed-meshheading:11719808-Retinoblastoma Protein,
pubmed-meshheading:11719808-S Phase,
pubmed-meshheading:11719808-Transcription Factors,
pubmed-meshheading:11719808-Viral Proteins
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pubmed:year |
2001
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pubmed:articleTitle |
The E2F1-3 transcription factors are essential for cellular proliferation.
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pubmed:affiliation |
Division of Human Cancer Genetics, Department of Molecular Virology, Immunology and Medical Genetics, and Department of Molecular Genetics, The Ohio State University, Columbus, Ohio 43210, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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