title: The anaphase-promoting complex or cyclosome supports cell survival in response to endoplasmic reticulum stress.
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.
authors.affiliation: Signal Transduction Program, Sanford-Burnham Medical Research Institute, La Jolla, California, United States of America.
authors.forename: Meifan
authors.initials: M
authors.lastname: Chen
authors.forename: Gustavo J
authors.initials: GJ
authors.lastname: Gutierrez
authors.forename: Ze'ev A
authors.initials: ZA
authors.lastname: Ronai
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome; D015703:Antigens, CD; D015820:Cadherins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints; D002470:Cell Survival; D059865:Endoplasmic Reticulum Stress; D016193:G1 Phase; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D034741:RNA, Small Interfering; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome