論文

2005年11月

Regulation of the Caenorhabditis elegans oxidative stress defense protein SKN-1 by glycogen synthase kinase-3

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
  • JH An
  • ,
  • K Vranas
  • ,
  • M Lucke
  • ,
  • H Inoue
  • ,
  • N Hisamoto
  • ,
  • K Matsumoto
  • ,
  • TK Blackwell

102
45
開始ページ
16275
終了ページ
16280
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1073/pnas.0508105102
出版者・発行元
NATL ACAD SCIENCES

Oxidative stress plays a central role in many human diseases and in aging. In Caenorhabditis elegans the SKN-1 protein induces phase II detoxification gene transcription, a conserved oxidative stress response, and is required for oxidative stress resistance and longevity. Oxidative stress induces SKN-1 to accumulate in intestinal nuclei, depending on p38 mitogen-activated protein kinase signaling. Here we show that, in the absence of stress, phosphorylation by glycogen synthase kinase-3 (GSK-3) prevents SKN-1 from accumulating in nuclei and functioning constitutively in the intestine. GSK-3 sites are conserved in mammalian SKN-1 orthologs, indicating that this level of regulation may be conserved. If inhibition by GSK-3 is blocked, background levels of p38 signaling are still required for SKN-1 function. WT and constitutively nuclear SKN-1 comparably rescue the skn-1 oxidative stress sensitivity, suggesting that an inducible phase II response may provide optimal stress protection. We conclude that (i) GSK-3 inhibits SKN-1 activity in the intestine, (h) the phase 11 response integrates multiple regulatory signals, and (fit), by inhibiting this response, GSK-3 may influence redox conditions.

リンク情報
DOI
https://doi.org/10.1073/pnas.0508105102
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000233283700028&DestApp=WOS_CPL
ID情報
  • DOI : 10.1073/pnas.0508105102
  • ISSN : 0027-8424
  • Web of Science ID : WOS:000233283700028

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