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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Active Transport, Cell Nucleus / physiology
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Animals
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Caenorhabditis elegans / cytology
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Caenorhabditis elegans / physiology*
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Caenorhabditis elegans Proteins / metabolism*
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Cell Nucleus / metabolism*
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DNA-Binding Proteins / metabolism*
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Gene Expression Regulation / physiology
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Intestines / cytology
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Intestines / physiology
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MAP Kinase Signaling System / physiology*
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Mitogen-Activated Protein Kinases / metabolism*
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Oxidative Stress / physiology*
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Transcription Factors / metabolism*
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Transcription, Genetic / physiology
Substances
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Caenorhabditis elegans Proteins
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DNA-Binding Proteins
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Transcription Factors
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skn-1 protein, C elegans
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Mitogen-Activated Protein Kinases
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Pmk-1 protein, C elegans