title: p34 (SEI-1) inhibits ROS-induced cell death through suppression of ASK1.
abstract: Apoptosis signal-regulating kinase 1 (ASK1) is a key factor for controlling several cellular events including the cell cycle, senescence and apoptosis, in response to reactive oxygen species (ROS). However, the mechanisms that regulate ASK1 protein levels remain largely unexplored. In this study, we demonstrate that p34 (SEI-1) , a positive cell cycle regulator with an oncogenic potential, inhibits ROS-induced cell death by suppressing ASK1. We first found that p34 (SEI-1) -expressing cells have enhanced resistance to hydrogen peroxide (H 2O 2). Moreover, ectopic expression of p34 (SEI-1) clearly inhibited H 2O 2-induced phosphorylation of ASK1 in the colon cancer cell lines- HCT116 and SW620-in association with a decrease in ASK1 protein levels. Interestingly, p34 (SEI-1) induced ubiquitination of ASK1, however, no direct interaction was found between p34 (SEI-1) and ASK1. These results suggest that p34 (SEI-1) inhibits ROS-induced cell death through by indirectly inducing ubiquitination of ASK1.
authors: Institute for Innovative Cancer Research, University of Ulsan, Asan Medical Center, Seoul, Korea.
authors: Seung-Woo
authors: SW
authors: Hong
authors: Jae-Sik
authors: JS
authors: Shin
authors: Young-Min
authors: YM
authors: Lee
authors: Dong-Gil
authors: DG
authors: Kim
authors: Sok-Young
authors: SY
authors: Lee
authors: Dok Hyun
authors: DH
authors: Yoon
authors: Seong-Yun
authors: SY
authors: Jung
authors: Jung Jin
authors: JJ
authors: Hwang
authors: Seung-Jin
authors: SJ
authors: Lee
authors: Dong-Hyung
authors: DH
authors: Cho
authors: Yong-Sang
authors: YS
authors: Hong
authors: Tae-Won
authors: TW
authors: Kim
authors: Dong-Hoon
authors: DH
authors: Jin
authors: Won-Keun
authors: WK
authors: Lee
mesh_terms: D017209:Apoptosis; D002453:Cell Cycle; D002460:Cell Line; D003110:Colonic Neoplasms / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D025801:Ubiquitin; D054875:Ubiquitination
chemical_list: D051034:Inhibitor of Apoptosis Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C402464:SERTAD1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025801:Ubiquitin; D006861:Hydrogen Peroxide; D048848:MAP Kinase Kinase Kinase 5; C482858:MAP3K5 protein, human