Search

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 p34SEI-1clearly 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, p34SEI-1induced ubiquitination of ASK1, however, no direct interaction was found between p34SEI-1and ASK1. These results suggest that p34SEI-1inhibits ROS-induced cell death through by indirectly inducing ubiquitination of ASK1.