Caspase-9: structure, mechanisms and clinical application

// Ping Li 1,2,3 , Libin Zhou 1 , Ting Zhao 1,2,3 , Xiongxiong Liu 1,2,3 , Pengcheng Zhang 1,2,3,4 , Yan Liu 1,2,3,4 , Xiaogang Zheng 1,2,3,4 and Qiang Li 1,2,3 1 Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, People’s Republic of China 2 Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou, People’s Republic of China 3 Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou, People’s Republic of China 4 University of Chinese Academy of Sciences, Beijing, People’s Republic of China Correspondence to: Qiang Li, email: // Keywords : caspase-9, apoptosis, phosphorylation, alternative splicing, iCasp9 Received : October 12, 2016 Accepted : January 22, 2017 Published : February 04, 2017 Abstract As the most intensively studied initiator caspase, caspase-9 is a key player in the intrinsic or mitochondrial pathway which is involved in various stimuli, including chemotherapies, stress agents and radiation. Caspase-9 is activated on the apoptosome complex to remain catalytic status and is thought of involving homo-dimerization monomeric zymogens. Failing to activate caspase-9 has profound physiological and pathophysiological outcomes, leading to degenerative and developmental disorders even cancer. To govern the apoptotic commitment process appropriately, plenty of proteins and small molecules involved in regulating caspase-9. Therefore, this review is to summarize recent pertinent literature on the comprehensive description of the molecular events implicated in caspase-9 activation and inhibition, as well as the clinical trials in progress to give deep insight into caspase-9 for suppressing cancer. We hope that our concerns will be helpful for further clinical studies addressing the roles of caspase-9 and its regulators demanded to identify more effective solutions to overcome intrinsic apoptosis-related diseases especially cancer.