p34sei-1 inhibits ros-induced cell death through suppression of ASK1

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 (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 p34^SEI-1 and ASK1. These results suggest that p34SEI-1 inhibits ROS-induced cell death through by indirectly inducing ubiquitination of ASK1.