Proteolysis of CDH1 enhances susceptibility to UV radiation-induced apoptosis.
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.
Liu
Weijun
W
Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213-1863, USA.
Li
Wenqi
W
Fujita
Takeo
T
Yang
Qi
Q
Wan
Yong
Y
D015703:Antigens, CD; D017209:Apoptosis; D016203:CDC2 Protein Kinase / Q000378:metabolism; D015820:Cadherins / Q000737:chemistry* / Q000378:metabolism; D002453:Cell Cycle; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D004249:DNA Damage; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D025801:Ubiquitin / Q000378:metabolism*; D014466:Ultraviolet Rays
D015703:Antigens, CD; C534699:CCNB1 protein, human; C513384:CDH1 protein, human; D015820:Cadherins; D019926:Cyclin B; D056744:Cyclin B1; D025801:Ubiquitin; D016203:CDC2 Protein Kinase; D046988:Proteasome Endopeptidase Complex