The C. elegans p38 MAPK pathway regulates nuclear localization of the transcription factor SKN-1 in oxidative stress response
- Hideki Inoue1,
- Naoki Hisamoto1,
- Jae Hyung An2,
- Riva P. Oliveira2,
- Eisuke Nishida3,
- T. Keith Blackwell2, and
- Kunihiro Matsumoto1,4
- 1Department of Molecular Biology, Graduate School of Science, Institute for Advanced Research, Nagoya University, and CREST, Japan Science and Technology Corporation, Chikusa-ku, Nagoya 464-8602, Japan; 2Section of Developmental and Stem Cell Biology, Joslin Diabetes Center and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02215, USA; 3Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan
Abstract
The evolutionarily conserved p38 mitogen-activated protein kinase (MAPK) cascade is an integral part of the response to a variety of environmental stresses. Here we show that the Caenorhabditis elegans PMK-1 p38 MAPK pathway regulates the oxidative stress response via the CNC transcription factor SKN-1. In response to oxidative stress, PMK-1 phosphorylates SKN-1, leading to its accumulation in intestine nuclei, where SKN-1 activates transcription of gcs-1, a phase II detoxification enzyme gene. These results delineate the C. elegans p38 MAPK signaling pathway leading to the nucleus that responds to oxidative stress.
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Footnotes
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Supplemental material is available at http://www.genesdev.org.
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Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.1324805.
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↵4 Corresponding author.
↵4 E-MAIL g44177a{at}nucc.cc.nagoya-u.ac.jp; FAX 011-81-52-789-2589.
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- Accepted August 3, 2005.
- Received April 19, 2005.
- Cold Spring Harbor Laboratory Press
