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

Authors: Oh, Seung Wook; Mukhopadhyay, Arnab; Svrzikapa, Nenad; Jiang, Feng; Davis, Roger J; Tissenbaum, Heidi A

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.

Keywords: Active Transport, Cell Nucleus; Animals; Animals, Genetically Modified; Base Sequence; Caenorhabditis elegans/*genetics/*physiology; Caenorhabditis elegans Proteins/*genetics/*physiology; DNA, Helminth/genetics; Genes, Helminth; Longevity/*genetics/*physiology; Mitogen-Activated Protein Kinase 8/*genetics/*physiology; Models, Biological; Phosphorylation; Signal Transduction; Transcription Factors/*genetics/*physiology
Journal: Proc Natl Acad Sci U S A
Volume: 102
Issue: 12
Pages: 4494-9
Date: March 16, 2005
PMID: 15767565
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Citation:

Oh, Seung Wook, Mukhopadhyay, Arnab, Svrzikapa, Nenad, Jiang, Feng, Davis, Roger J, Tissenbaum, Heidi A (2005) JNK regulates lifespan in Caenorhabditis elegans by modulating nuclear translocation of forkhead transcription factor/DAF-16. Proc Natl Acad Sci U S A 102: 4494-9.


Study Lifespan Factors:
  • jnk-1 Jun N-terminal Kinase


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