Document Detail

Proteolysis of CDH1 enhances susceptibility to UV radiation-induced apoptosis.
MedLine Citation:
PMID:  18174259     Owner:  NLM     Status:  MEDLINE    
As a critical ubiquitin ligase, the anaphase-promoting complex/cyclosome (APC/C) governs cell cycle progression, signaling modulation and the pathogenesis of some human diseases. Recent studies implicate APC in maintaining genomic integrity, but the mechanism by which it plays such a role remains largely unknown. We report here that acute UV radiation triggers proteolysis of CDH1, an activator of APC, which is involved in regulation of apoptosis induced by UV radiation. Depletion of CDH1 by RNA interference enhances the cellular susceptibility to apoptosis in response to UV radiation, whereas overexpression of non-degradable CDH1 delays UV radiation-induced apoptosis. In addition, UV-induced degradation of CDH1 results in the accumulation of cyclin B1 and therefore to increased CDK1 activity, which is believed to enhance UV-induced apoptosis. The present results unveil a novel role for the APC in UV-induced cell death and demonstrate a new regulatory mechanism for APC/CDH1 through proteolysis.
Weijun Liu; Wenqi Li; Takeo Fujita; Qi Yang; Yong Wan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-01-03
Journal Detail:
Title:  Carcinogenesis     Volume:  29     ISSN:  1460-2180     ISO Abbreviation:  Carcinogenesis     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-03-03     Completed Date:  2008-03-25     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  England    
Other Details:
Languages:  eng     Pagination:  263-72     Citation Subset:  IM    
Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213-1863, USA.
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MeSH Terms
CDC2 Protein Kinase / metabolism
Cadherins / chemistry*,  metabolism
Cell Cycle
Cyclin B / metabolism
Cyclin B1
DNA Damage
Genetic Vectors
Hela Cells
Microscopy, Fluorescence
Models, Biological
Proteasome Endopeptidase Complex / metabolism*
Protein Structure, Tertiary
Ubiquitin / metabolism*
Ultraviolet Rays*
Grant Support
Reg. No./Substance:
0/CCNB1 protein, human; 0/CDH1 protein, human; 0/Cadherins; 0/Cyclin B; 0/Cyclin B1; 0/Ubiquitin; EC Protein Kinase; EC Endopeptidase Complex

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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