Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans.

Authors: Tullet JM; Hertweck M; An JH; Baker J; Hwang JY; Liu S; Oliveira RP; Baumeister R; Blackwell TK
Year: 2008
Journal: Cell
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.
Reference

Integration:

Created on Nov. 5, 2012, 5:59 p.m.
Not linked
Integrated: False

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Species: Nematode

Experiments: 0
Interventions:

Overexpression of constitutive nuclear SKN-1

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