Document Detail


Disruption of Trrap causes early embryonic lethality and defects in cell cycle progression.
MedLine Citation:
PMID:  11544477     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Z Herceg; W Hulla; D Gell; C Cuenin; M Lleonart; S Jackson; Z Q Wang
Related Documents :
19633697 - Cdc5l interacts with atr and is required for the s-phase cell-cycle checkpoint.
9008167 - Association of brca1 with rad51 in mitotic and meiotic cells.
11479327 - Analysis of cell division parameters and cell cycle gene expression during the cultivat...
20945347 - Mechanisms of transforming growth factor β induced cell cycle arrest in palate develop...
21547417 - Idebenone induces apoptotic cell death in the human dopaminergic neuroblastoma shsy-5y ...
7427917 - Potentiating effect of cigarette smoke extract on morphological transformation of hamst...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nature genetics     Volume:  29     ISSN:  1061-4036     ISO Abbreviation:  Nat. Genet.     Publication Date:  2001 Oct 
Date Detail:
Created Date:  2001-10-04     Completed Date:  2001-12-04     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9216904     Medline TA:  Nat Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  206-11     Citation Subset:  IM    
Affiliation:
International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, F-69008, Lyon, France.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
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:
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


Previous Document:  Hypotrichosis with juvenile macular dystrophy is caused by a mutation in CDH3, encoding P-cadherin.
Next Document:  Pharmacologic rescue of lethal seizures in mice deficient in succinate semialdehyde dehydrogenase.