JNK regulates lifespan in Caenorhabditis elegans by modulating nuclear translocation of forkhead transcription factor/DAF-16
Program in Gene Function and Expression; Program in Molecular Medicine
Active Transport, Cell Nucleus; Animals; Animals, Genetically Modified; Base Sequence; Caenorhabditis elegans; Caenorhabditis elegans Proteins; DNA, Helminth; Genes, Helminth; Longevity; Mitogen-Activated Protein Kinase 8; Models, Biological; Phosphorylation; Signal Transduction; Transcription Factors
Life Sciences | Medicine and Health Sciences
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.
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Citation: Proc Natl Acad Sci U S A. 2005 Mar 22;102(12):4494-9. Epub 2005 Mar 14. Link to article on publisher's site