Journal Article

Proteolysis of CDH1 enhances susceptibility to UV radiation-induced apoptosis

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

in Carcinogenesis

Volume 29, issue 2, pages 263-272
Published in print February 2008 | ISSN: 0143-3334
Published online January 2008 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgm251
Proteolysis of CDH1 enhances susceptibility to UV radiation-induced apoptosis

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  • Clinical Cytogenetics and Molecular Genetics

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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.

Journal Article.  6993 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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