PMID:18358814

Citation	Tullet, JM, Hertweck, M, An, JH, Baker, J, Hwang, JY, Liu, S, Oliveira, RP, Baumeister, R and Blackwell, TK (2008) Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans. Cell 132:1025-38
Abstract	Insulin/IGF-1-like signaling (IIS) is central to growth and metabolism and has a conserved role in aging. In C. elegans, reductions in IIS increase stress resistance and longevity, effects that require the IIS-inhibited FOXO protein DAF-16. The C. elegans transcription factor SKN-1 also defends against oxidative stress by mobilizing the conserved phase 2 detoxification response. Here we show that IIS not only opposes DAF-16 but also directly inhibits SKN-1 in parallel. The IIS kinases AKT-1, -2, and SGK-1 phosphorylate SKN-1, and reduced IIS leads to constitutive SKN-1 nuclear accumulation in the intestine and SKN-1 target gene activation. SKN-1 contributes to the increased stress tolerance and longevity resulting from reduced IIS and delays aging when expressed transgenically. Furthermore, SKN-1 that is constitutively active increases life span independently of DAF-16. Our findings indicate that the transcription network regulated by SKN-1 promotes longevity and is an important direct target of IIS.
Links	PubMed PMC2367249 Online version:10.1016/j.cell.2008.01.030
Keywords	Animals; Caenorhabditis elegans/physiology; Caenorhabditis elegans Proteins/metabolism; DNA-Binding Proteins/metabolism; Gene Regulatory Networks; Insulin/metabolism; Insulin-Like Growth Factor I/metabolism; Intestines; Longevity; Oxidative Stress; Phosphorylation; Receptor, Insulin/metabolism; Signal Transduction; Transcription Factors/metabolism
edit table

Annotations

Gene product	Qualifier	GO ID	GO term name	Evidence Code	with/from	Aspect	Notes	Status
edit table

References

See Help:References for how to manage references in GONUTS.