p34 (SEI-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 (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.