JNK regulates lifespan in Caenorhabditis elegans by modulating nuclear translocation of forkhead transcription factor/DAF-16.
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.
Oh
Seung Wook
SW
Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Mukhopadhyay
Arnab
A
Svrzikapa
Nenad
N
Jiang
Feng
F
Davis
Roger J
RJ
Tissenbaum
Heidi A
HA
D021581:Active Transport, Cell Nucleus; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000502:physiology*; D018509:DNA, Helminth / Q000235:genetics; D051858:Forkhead Transcription Factors; D017238:Genes, Helminth; D008136:Longevity / Q000235:genetics* / Q000502:physiology*; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics* / Q000502:physiology*; D008954:Models, Biological; D010766:Phosphorylation; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; D018509:DNA, Helminth; D051858:Forkhead Transcription Factors; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; D048055:Mitogen-Activated Protein Kinase 8