The ERK-MAPK pathway regulates longevity through SKN-1 and insulin-like signaling in Caenorhabditis elegans

75Citations
Citations of this article
152Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

It has not been determined yet whether the ERK-MAPK pathway regulates longevity of metazoans. Here, we show that the Caenorhabditis elegans ERK cascade promotes longevity through the two longevity-promoting transcription factors, SKN-1 and DAF-16. We find that RNAi of three genes, which constitute the ERK cascade (lin-45/RAF1, mek-2/MEK1/2, and mpk-1/ERK1/2), results in reduction of life span. Moreover, RNAi of lip-1, the gene encoding a MAPK phosphatase that inactivates MPK-1, increases life span. Epistasis analyses show that the ERK (MPK-1) cascade-mediated life span extension requires SKN-1, whose function is mediated, at least partly, through DAF-2/DAF-16 insulin-like signaling. MPK-1 phosphorylates SKN-1 on the key sites that are required for SKN-1 nuclear accumulation. Our results also show that one mechanism by which SKN-1 regulates insulin-like signaling is through the regulation of expression of insulin-like peptides. Our findings thus identify a novel ERK-MAPK-mediated signaling pathway that promotes longevity. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.

Cite

CITATION STYLE

APA

Okuyama, T., Inoue, H., Ookuma, S., Satoh, T., Kano, K., Honjoh, S., … Nishida, E. (2010). The ERK-MAPK pathway regulates longevity through SKN-1 and insulin-like signaling in Caenorhabditis elegans. Journal of Biological Chemistry, 285(39), 30274–30281. https://doi.org/10.1074/jbc.M110.146274

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free