• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

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

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.

Pubmed ID: 18358814

Authors

  • Tullet JM
  • Hertweck M
  • An JH
  • Baker J
  • Hwang JY
  • Liu S
  • Oliveira RP
  • Baumeister R
  • Blackwell TK

Journal

Cell

Publication Data

March 21, 2008

Associated Grants

  • Agency: NIGMS NIH HHS, Id: 2 R01 GM062891
  • Agency: NIGMS NIH HHS, Id: 5 F32 GM070088-02
  • Agency: NIGMS NIH HHS, Id: R01 GM062891
  • Agency: NIGMS NIH HHS, Id: R01 GM062891-05
  • Agency: NIGMS NIH HHS, Id: R01 GM062891-06
  • Agency: NIGMS NIH HHS, Id: R01 GM062891-07
  • Agency: NIGMS NIH HHS, Id: R01 GM062891-08
  • Agency: NIDDK NIH HHS, Id: T32 DK07260

Mesh Terms

  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • Gene Regulatory Networks
  • Insulin
  • Insulin-Like Growth Factor I
  • Intestines
  • Longevity
  • Oxidative Stress
  • Phosphorylation
  • Receptor, Insulin
  • Signal Transduction
  • Transcription Factors