Document Detail

Dual mode of regulation of cell division cycle 25 A protein by TRB3.
MedLine Citation:
PMID:  20606298     Owner:  NLM     Status:  MEDLINE    
We have recently demonstrated that TRB3, a novel stress-inducible protein, is an unstable protein regulated by the ubiquitin-proteasome system. The expression level of TRB3 protein is down-regulated by anaphase-promoting complex/cyclosome-cell division cycle division 20 homolog 1 (APC/C(Cdh1)) through its D-box motif. Here we demonstrate that TRB3 regulates the stability of cell division cycle 25 A (Cdc25A), an essential activator of cyclin dependent kinases (CDKs). The expression level of Cdc25A protein is suppressed by over-expression of TRB3, while knockdown of TRB3 enhances the endogenous Cdc25A expression level. On the other hand, Cdc25A degradation induced by DNA damage is significantly rescued by TRB3. When serine residues in the DSG motif, which is the critical sequences for the degradation of Cdc25A induced by DNA damage, is mutated to alanine (Cdc25A(DSG2X)), both stimulatory and protective effects of TRB3 on the Cdc25A degradation is disappeared. TRB3 protein interacts with both wild Cdc25A and mutant Cdc25A(DSG2X). Expression level of the endogenous TRB3 protein is down-regulated in a genotoxic condition. These results suggest TRB3 is a regulator for adjusting the expression level of Cdc25A both in a normal and a genotoxic conditions.
Satoshi Sakai; Nobumichi Ohoka; Kikuo Onozaki; Masatoshi Kitagawa; Makoto Nakanishi; Hidetoshi Hayashi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biological & pharmaceutical bulletin     Volume:  33     ISSN:  1347-5215     ISO Abbreviation:  Biol. Pharm. Bull.     Publication Date:  2010  
Date Detail:
Created Date:  2010-07-07     Completed Date:  2010-11-26     Revised Date:  2012-07-03    
Medline Journal Info:
Nlm Unique ID:  9311984     Medline TA:  Biol Pharm Bull     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  1112-6     Citation Subset:  IM    
Department of Drug Metabolism and Disposition, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.
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MeSH Terms
Blotting, Western
Cell Cycle Proteins / physiology*
Cell Line
DNA Damage
Protein-Serine-Threonine Kinases / physiology*
RNA Interference
Repressor Proteins / physiology*
cdc25 Phosphatases / physiology*
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Repressor Proteins; 0/TRIB3 protein, human; EC Kinases; EC protein, human; EC Phosphatases

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