論文

査読有り
2010年9月

The ERK-MAPK Pathway Regulates Longevity through SKN-1 and Insulin-like Signaling in Caenorhabditis elegans

JOURNAL OF BIOLOGICAL CHEMISTRY
  • Tetsuya Okuyama
  • ,
  • Hideki Inoue
  • ,
  • Sadatsugu Ookuma
  • ,
  • Takayuki Satoh
  • ,
  • Kei Kano
  • ,
  • Sakiko Honjoh
  • ,
  • Naoki Hisamoto
  • ,
  • Kunihiro Matsumoto
  • ,
  • Eisuke Nishida

285
39
開始ページ
30274
終了ページ
30281
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1074/jbc.M110.146274
出版者・発行元
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

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.

Web of Science ® 被引用回数 : 62

リンク情報
DOI
https://doi.org/10.1074/jbc.M110.146274
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/20624915
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000281984300063&DestApp=WOS_CPL
ID情報
  • DOI : 10.1074/jbc.M110.146274
  • ISSN : 0021-9258
  • eISSN : 1083-351X
  • PubMed ID : 20624915
  • Web of Science ID : WOS:000281984300063

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