Effects of Caenorhabditis elegans sgk-1 mutations on lifespan, stress resistance, and DAF-16/FoxO regulation.
Bottom Line: Accordingly, unlike AKT-1, which promotes the cytoplasmic sequestration of DAF-16/FoxO, SGK-1 does not influence DAF-16/FoxO subcellular localization.Thus, in spite of their similar in vitro substrate specificities, Akt and Sgk influence longevity, stress resistance, and FoxO activity through distinct mechanisms in vivo.Our findings highlight the need for a re-evaluation of current paradigms of FoxO regulation by Sgk.
Affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, Michigan.Show MeSH
Related in: MedlinePlus
Mentions: In light of our observations on the effects of sgk-1 mutations on lifespan (Fig. 1), we tested sgk-1() and sgk-1(gf) for their sensitivity to oxidative stress, ultraviolet radiation (UVR), and heat. akt-1 mutants were slightly more resistant to hydrogen peroxide than wild-type animals, although this difference was only statistically significant in one of four assays (Fig. 2A,B and Table S2). akt-1 mutants were significantly more resistant to UVR and heat than wild-type animals (Fig. 2C–F and Tables S3 and S4). In contrast, both sgk-1 mutants were more sensitive to hydrogen peroxide (statistically significant in 2 of 3 trials for each mutant) and UVR (statistically significant in 3 of 3 trials) than wild-type animals (Fig. 2A,C and Tables S3–4), consistent with their short lifespans (Fig. 1B and Table S1). sgk-1(gf) did not significantly influence sensitivity to any of the three stressors tested (Fig. 2B,D,F and Tables S3–5).
Affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, Michigan.