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

Tullet, Jennifer M.A., Hertweck, Maren, An, Jae Hyung, Baker, Joseph, Hwang, Ji Yun, Liu, Shu, Oliveira, Riva P, Baumeister, Ralf, Blackwell, T Keith (2008) Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans. Cell, 132 (6). pp. 1025-1038. ISSN 1097-4172. (doi:10.1016/j.cell.2008.01.030) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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Official URL
http://dx.doi.org/10.1016/j.cell.2008.01.030

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.

Item Type: Article
DOI/Identification number: 10.1016/j.cell.2008.01.030
Subjects: Q Science > Q Science (General)
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Jennifer Tullet
Date Deposited: 13 Oct 2014 08:17 UTC
Last Modified: 29 May 2019 13:09 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/43249 (The current URI for this page, for reference purposes)
Tullet, Jennifer M.A.: https://orcid.org/0000-0002-2037-526X
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