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PLoS One. 2012;7(4):e35520. doi: 10.1371/journal.pone.0035520. Epub 2012 Apr 23.

The anaphase-promoting complex or cyclosome supports cell survival in response to endoplasmic reticulum stress.

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1
Signal Transduction Program, Sanford-Burnham Medical Research Institute, La Jolla, California, United States of America.

Abstract

The anaphase-promoting complex or cyclosome (APC/C) is a multi-subunit ubiquitin ligase that regulates exit from mitosis and G1 phase of the cell cycle. Although the regulation and function of APC/C(Cdh1) in the unperturbed cell cycle is well studied, little is known of its role in non-genotoxic stress responses. Here, we demonstrate the role of APC/C(Cdh1) (APC/C activated by Cdh1 protein) in cellular protection from endoplasmic reticulum (ER) stress. Activation of APC/C(Cdh1) under ER stress conditions is evidenced by Cdh1-dependent degradation of its substrates. Importantly, the activity of APC/C(Cdh1) maintains the ER stress checkpoint, as depletion of Cdh1 by RNAi impairs cell cycle arrest and accelerates cell death following ER stress. Our findings identify APC/C(Cdh1) as a regulator of cell cycle checkpoint and cell survival in response to proteotoxic insults.

PMID:
22539978
PMCID:
PMC3335095
DOI:
10.1371/journal.pone.0035520
[Indexed for MEDLINE]
Free PMC Article
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