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 p34SEI-1 a positive cell cycle regulator with an oncogenic potential inhibits ROS-induced cell death by suppressing ASK1. We first found that p34SEI-1-expressing cells have enhanced resistance to hydrogen peroxide (H2O2). Moreover ectopic expression of p34 SEI-1 clearly inhibited H2O2- 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 p34SEI-1 and ASK1. These results suggest that p34SEI-1 inhibits ROS-induced cell death through by indirectly inducing ubiquitination of ASK1.
Bibliographical noteFunding Information:
This study was supported by grants from the Korea Health 21 R&D Project, Ministry of Health and Welfare and Family Affairs, Republic of Korea (A062254), and the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (20100015972).