TY - JOUR
T1 - The anaphase-promoting complex or cyclosome supports cell survival in response to endoplasmic reticulum stress
AU - Chen, Meifan
AU - Gutierrez, Gustavo J.
AU - Ronai, Ze'ev A.
PY - 2012/4/23
Y1 - 2012/4/23
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0035520
DO - 10.1371/journal.pone.0035520
M3 - Article
C2 - 22539978
AN - SCOPUS:84859941675
SN - 1932-6203
VL - 7
JO - PLoS ONE
JF - PLoS ONE
IS - 4
M1 - e35520
ER -