| Control of the p53-p21CIP1 Axis by E2f1, E2f2, and E2f3 is essential for G1/S progression and cellular transformation. | |
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MedLine Citation:
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PMID: 17008321 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The E2F family of transcription factors is believed to have an essential role in the control of cellular proliferation by regulating the transcription of genes involved in cell cycle progression. Previous work has demonstrated that the targeted inactivation of E2f1, E2f2, and E2f3 results in elevated p21(CIP1) protein levels, loss of E2F target gene expression, and cell cycle arrest at G1/S and G2/M, suggesting a strict requirement for these E2Fs in the control of normal cellular proliferation. We now demonstrate that E2f1, E2f2, and E2f3 are also required for oncogene-mediated transformation of mouse embryonic fibroblasts. Analysis of synchronized populations of mouse embryonic fibroblasts revealed that the inactivation of p21(CIP1) restores the ability of E2f1-3-deficient cells to enter and transit through G1/S (but not G2/M). In contrast, loss of p53 restored the ability of these cells to progress through both G1/S and mitosis, leading to their continued proliferation. The inactivation of p53 (but not p21(CIP1)) rendered E2f1-3-deficient cells sensitive to transformation and tumorigenesis. These results suggest that the negative regulation of the p53-p21(CIP1) axis by the E2F1-3 factors is critical for cell cycle progression and cellular transformation. |
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Authors:
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Nidhi Sharma; Cynthia Timmers; Prashant Trikha; Harold I Saavedra; Amanda Obery; Gustavo Leone |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2006-09-27 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 281 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2006 Nov |
Date Detail:
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Created Date: 2006-11-20 Completed Date: 2007-01-09 Revised Date: 2007-12-03 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 36124-31 Citation Subset: IM |
Affiliation:
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Human Cancer Genetics Program, Department of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, Ohio 43210, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Cycle Cell Nucleus / metabolism Cell Transformation, Neoplastic* Cyclin-Dependent Kinase Inhibitor p21 / physiology* E2F1 Transcription Factor / physiology* E2F2 Transcription Factor / physiology* E2F3 Transcription Factor / physiology* G1 Phase Male Mice Mice, Transgenic Models, Biological S Phase Tumor Suppressor Protein p53 / physiology* |
| Grant Support | |
ID/Acronym/Agency:
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K01CA104079/CA/NCI NIH HHS; P01CA097189/CA/NCI NIH HHS; R01 CA85619/CA/NCI NIH HHS; R01CA82259/CA/NCI NIH HHS; R01HD047470/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cdkn1a protein, mouse; 0/Cyclin-Dependent Kinase Inhibitor p21; 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/Tumor Suppressor Protein p53 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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