Title

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

UMMS Affiliation

Program in Gene Function and Expression; Program in Molecular Medicine

Date

3-16-2005

Document Type

Article

Subjects

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

Disciplines

Life Sciences | Medicine and Health Sciences

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.

Rights and Permissions

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

Related Resources

Link to Article in PubMed

Journal Title

Proceedings of the National Academy of Sciences of the United States of America

PubMed ID

15767565