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Proc Natl Acad Sci U S A. 2005 Mar 22;102(12):4494-9. Epub 2005 Mar 14.

JNK regulates lifespan in Caenorhabditis elegans by modulating nuclear translocation of forkhead transcription factor/DAF-16.

Author information

  • 1Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA 01605, USA.

Abstract

DAF-16/forkhead transcription factor, the downstream target of the insulin-like signaling in Caenorhabditis elegans, is indispensable for both lifespan regulation and stress resistance. Here, we demonstrate that c-Jun N-terminal kinase (JNK) is a positive regulator of DAF-16 in both processes. Our genetic analysis suggests that the JNK pathway acts in parallel with the insulin-like signaling pathway to regulate lifespan and both pathways converge onto DAF-16. We also show that JNK-1 directly interacts with and phosphorylates DAF-16. Moreover, in response to heat stress, JNK-1 promotes the translocation of DAF-16 into the nucleus. Our findings define an interaction between two well conserved proteins, JNK-1 and DAF-16, and provide a mechanism by which JNK regulates longevity and stress resistance.

Comment in

  • All roads lead to FoxO. [Cell Metab. 2005]
PMID:
15767565
[PubMed - indexed for MEDLINE]
PMCID:
PMC555525
Free PMC Article

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