the anaphase-promoting complex or cyclosome supports cell survival in response to endoplasmic reticulum stressanaphase-promoting复杂或cyclosome支持细胞生存在内质网应激反应.pdfVIP

The Anaphase-Promoting Complex or Cyclosome Supports Cell Survival in Response to Endoplasmic Reticulum Stress ¤ Meifan Chen, Gustavo J. Gutierrez , Ze’ev A. Ronai* 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/CCdh1 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/CCdh1 (APC/C activated by Cdh1 protein) in cellular protection from endoplasmic reticulum (ER) stress. Activation of APC/CCdh1 under ER stress conditions is evidenced by Cdh1-dependent degradation of its substrates. Importantly, the activity of APC/CCdh1 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/CCdh1 as a regulator of cell cycle checkpoint and cell survival in response to proteotoxic insults. Citation: Chen M, Gutierrez GJ, Ronai ZA (2012) The Anaphase-Promoting Complex or Cyclosome Supports Cell Survival in Response to Endoplasmic Reticulum Stress. PLoS ONE 7(4): e35520. doi:10.1371/journal.pone.0035520 Editor: Ming Tat Ling, Queensland University of Technology, Australia Received November 21, 2011; Accepted March 18, 2012; Published April 23, 2012 Copyright: 2012 Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the