The p38 signal transduction pathway participates in the oxidative stress-mediated translocation of DAF-16 to Caenorhabditis elegans nuclei.

Much attention has focused on the insulin-like signaling pathway in Caenorhabditis elegans because of its pivotal role in life-span determination and oxidative stress resistance. The daf-16 gene encodes a fork-head transcription factor that is negatively regulated by this insulin-signaling pathway. The DAF-16 protein is translocated to the nucleus when animals were subjected to oxidative stress in the form of paraquat. This oxidative stress-mediated translocation was blocked by mutation of the p38-related sek-1 (MAPKK) mutant and DAF-16 instead remained cytoplasmic. The fact that DAF-16 translocation by oxidative stress is epistatic to sek-1 suggests that oxidative stress mediates regulation of DAF-16 through activating the p38 signal transduction pathway upstream of daf-16 so as to mobilize DAF-16 to the nucleus and activate transcription.