| An E2F binding-deficient Rb1 protein partially rescues developmental defects associated with Rb1 nullizygosity. | |
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MedLine Citation:
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PMID: 16449662 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Rb1 is essential for normal embryonic development, as null mice die in midgestation with widespread unscheduled cell proliferation. Rb1 protein (pRb) mediates cell cycle control by binding E2F transcription factors and repressing expression from E2F-dependent promoters. An increasing amount of evidence suggests that pRb loss also compromises cellular differentiation. Since differentiation is often dependent on cell cycle exit, it is currently unclear whether the effects of pRb on differentiation are an indirect consequence of pRb/E2F-mediated cell cycle control or whether they reflect direct cell-type-specific pRb functions. We have mutated Rb1 in the mouse to express a protein (R654W) specifically deficient in binding E2F1, E2F2, and E2F3. R654W mutant embryos exhibit cell cycle defects the same as those of Rb1 null embryos, reinforcing the importance of the interactions of pRb with E2F1, E2F2, and E2F3 for cell cycle control. However, R654W embryos survive at least 2 days longer than Rb1 null embryos, and increased life span is associated with improved erythrocyte and fetal liver macrophage differentiation. In contrast, R654W pRb does not rescue differentiation defects associated with pRb-deficient retinae. These data indicate that Rb1 makes important cell-type-specific contributions to cellular differentiation that are genetically separable from its general ability to stably bind E2F1, E2F2, and E2F3 and regulate the cell cycle. |
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Authors:
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Huifang Sun; Yanjie Chang; Brett Schweers; Michael A Dyer; Xiaojing Zhang; Simon W Hayward; David W Goodrich |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Molecular and cellular biology Volume: 26 ISSN: 0270-7306 ISO Abbreviation: Mol. Cell. Biol. Publication Date: 2006 Feb |
Date Detail:
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Created Date: 2006-02-01 Completed Date: 2006-04-03 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 8109087 Medline TA: Mol Cell Biol Country: United States |
Other Details:
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Languages: eng Pagination: 1527-37 Citation Subset: IM |
Affiliation:
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Department of Pharmacology & Therapeutics, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY 14263, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alleles Amino Acid Substitution Animals Base Sequence Cell Cycle Congenital Abnormalities / genetics, pathology DNA / genetics E2F Transcription Factors / metabolism* Female Fetal Development / genetics, physiology Homozygote Male Mice Mice, Knockout Mice, Mutant Strains Mutagenesis, Site-Directed Pregnancy Recombinant Proteins / genetics, metabolism Retina / abnormalities Retinoblastoma Protein / deficiency, genetics*, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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CA70292/CA/NCI NIH HHS; CA96403/CA/NCI NIH HHS; EY014867/EY/NEI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/E2F Transcription Factors; 0/Recombinant Proteins; 0/Retinoblastoma Protein; 9007-49-2/DNA |
| Comments/Corrections | |
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