Kondo Masaki, Yanase Sumino, Ishii Takamasa, Hartman Philip S, Matsumoto Kunihiro, Ishii Naoaki
Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Mech Ageing Dev. 2005 Jun-Jul;126(6-7):642-7. doi: 10.1016/j.mad.2004.11.012. Epub 2005 Jan 11.
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.
由于胰岛素样信号通路在寿命决定和抗氧化应激中起关键作用，秀丽隐杆线虫中的该信号通路已备受关注。daf-16基因编码一种叉头转录因子，受此胰岛素信号通路的负调控。当动物受到百草枯形式的氧化应激时，DAF-16蛋白会转移至细胞核。p38相关的sek-1（MAPKK）突变体的突变会阻断这种氧化应激介导的转移，DAF-16反而会留在细胞质中。氧化应激导致的DAF-16转移对sek-1呈上位性，这一事实表明氧化应激通过激活daf-16上游的p38信号转导通路来介导对DAF-16的调控，从而将DAF-16转运至细胞核并激活转录。
