| Disruption of Trrap causes early embryonic lethality and defects in cell cycle progression. | |
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MedLine Citation:
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PMID: 11544477 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The transactivation/transformation-domain associated protein (TRRAP) belongs to the Ataxia-telangiectasia mutated (ATM) super-family and has been identified as a cofactor for c-MYC-mediated oncogenic transformation. TRRAP and its yeast homolog (Tra1p) are components of histone acetyltransferase (HAT) complexes, SAGA (refs. 2,4,5), PCAF (ref. 3) and NuA4 (ref. 6), which are important for the regulation of transcription and cell cycle progression and also have a role in cell viability. Yet the biological function of this molecule and how it controls proliferation are still unclear. Here we show that null mutation of Trrap in mice results in peri-implantation lethality due to a blocked proliferation of blastocysts. We use an inducible Cre-loxP system to show that loss of Trrap blocks cell proliferation because of aberrant mitotic exit accompanied by cytokinesis failure and endoreduplication. Trrap-deficient cells fail to sustain mitotic arrest despite chromosome missegregation and disrupted spindles, and display compromised cdk1 activity. Trrap is therefore essential for early development and required for the mitotic checkpoint and normal cell cycle progression. |
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Authors:
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Z Herceg; W Hulla; D Gell; C Cuenin; M Lleonart; S Jackson; Z Q Wang |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Nature genetics Volume: 29 ISSN: 1061-4036 ISO Abbreviation: Nat. Genet. Publication Date: 2001 Oct |
Date Detail:
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Created Date: 2001-10-04 Completed Date: 2001-12-04 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9216904 Medline TA: Nat Genet Country: United States |
Other Details:
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Languages: eng Pagination: 206-11 Citation Subset: IM |
Affiliation:
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International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, F-69008, Lyon, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adaptor Proteins, Signal Transducing Animals Base Sequence Cell Cycle / genetics* Cell Line DNA Primers Female Fetal Death / genetics* Genes, Lethal* Heterozygote Homozygote Mice Mice, Mutant Strains Nuclear Proteins / genetics* |
| Chemical | |
Reg. No./Substance:
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0/Adaptor Proteins, Signal Transducing; 0/DNA Primers; 0/Nuclear Proteins; 0/transformation-transcription domain-associated protein |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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