Phosphorylation of Caspase-9 by CDK1/Cyclin B1 Protects Mitotic Cells against Apoptosis

作者: Lindsey A. Allan , Paul R. Clarke

DOI: 10.1016/J.MOLCEL.2007.03.019

关键词: MitosisCancer researchCell cycleCyclin APhosphorylationCell biologyApoptosisCyclin-dependent kinase 1BiologyCyclin B1Cyclin B

摘要: Proliferating metazoan cells respond to damage that has the potential cause genomic instability by restricting cell division cycle or initiating apoptosis. The molecular mechanisms determining balance between these responses are not well understood. Here, we show apoptotic initiator protease caspase-9 is regulated during through periodic phosphorylation at an inhibitory site, Thr125. This site phosphorylated CDK1/cyclin B1 mitosis and in response microtubule poisons arrest this stage of cycle. Using RNA interference strategy, induction apoptosis from drugs dependent greatly increased when endogenous replaced a nonphosphorylatable mutant. Thus, Thr125 sets threshold for activation intrinsic pathway cycle, restrains mitosis, determines sensitivity antimitotic drugs.

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