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Carcinogenesis Advance Access originally published online on January 3, 2008
Carcinogenesis 2008 29(2):263-272; doi:10.1093/carcin/bgm251
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Proteolysis of CDH1 enhances susceptibility to UV radiation-induced apoptosis

Weijun Liu, Wenqi Li, Takeo Fujita, Qi Yang and Yong Wan*

Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213-1863

* To whom correspondence should be addressed: Tel: +1 412 623 3275; Fax: +1 412 623 7761; Email: yow4{at}pitt.edu

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.

Abbreviations: APC/C, anaphase-promoting complex/cyclosome; ATM, ataxia telangiectasia mutated; ATR, ataxia telangiectasia mutatedand Rad3 related; FACS, fluorescence-activated cell sorting; PBS, phosphate-buffered saline; PCR, polymerase chain reaction; SiRNA, Small interference RNA; FACS, flourescence-activated cell sorting

Received August 16, 2007; revised October 9, 2007; accepted November 3, 2007.


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