JNK regulates lifespan in Caenorhabditis elegans by modulating nuclear translocation of forkhead transcription factor/DAF-16
- Seung Wook Oh*,†,
- Arnab Mukhopadhyay*,†,
- Nenad Svrzikapa*,†,
- Feng Jiang†,
- Roger J. Davis†,‡, and
- Heidi A. Tissenbaum*,†,§
- Programs in *Gene Function and Expression and †Molecular Medicine and ‡Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, MA 01605
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Communicated by Frederick M. Ausubel, Harvard Medical School, Boston, MA, January 31, 2005 (received for review December 29, 2004)
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.
Footnotes
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↵ § To whom correspondence should be addressed. E-mail: heidi.tissenbaum{at}umassmed.edu.
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Author contributions: S.W.O., A.M., R.J.D., and H.A.T. designed research; S.W.O., A.M., N.S., and F.J. performed research; S.W.O., and H.A.T. contributed new reagents/analytic tools; S.W.O., A.M., N.S., F.J., R.J.D., and H.A.T. analyzed data; and S.W.O., A.M., R.J.D., and H.A.T. wrote the paper.
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Abbreviations: AKT, protein kinase B; JNK, c-Jun N-terminal kinase; NGM, nematode growth medium; RNAi, RNA interference.
- Copyright © 2005, The National Academy of Sciences
