Abstract
The Schizosaccharomyces pombe stress-activated Sty1p/Spc1p mitogen-activated protein (MAP) kinase regulates gene expression through the Atf1p and Pap1p transcription factors, homologs of human ATF2 and c-Jun, respectively. Mcs4p, a response regulator protein, acts upstream of Sty1p by binding the Wak1p/Wis4p MAP kinase kinase kinase. We show that phosphorylation of Mcs4p on a conserved aspartic acid residue is required for activation of Sty1p only in response to peroxide stress. Mcs4p acts in a conserved phospho-relay system initiated by two PAS/PAC domain-containing histidine kinases, Mak2p and Mak3p. In the absence of Mak2p or Mak3p, Sty1p fails to phosphorylate the Atf1p transcription factor or induce Atf1p-dependent gene expression. As a consequence, cells lacking Mak2p and Mak3p are sensitive to peroxide attack in the absence of Prr1p, a distinct response regulator protein that functions in association with Pap1p. The Mak1p histidine kinase, which also contains PAS/PAC repeats, does not regulate Sty1p or Atf1p but is partially required for Pap1p- and Prr1p-dependent transcription. We conclude that the transcriptional response to free radical attack is initiated by at least two distinct phospho-relay pathways in fission yeast.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Activating Transcription Factor 1
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Amino Acid Sequence
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Base Sequence
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Basic-Leucine Zipper Transcription Factors
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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DNA-Binding Proteins / metabolism
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Enzyme Activation / drug effects
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Free Radicals / metabolism
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Fungal Proteins / genetics
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Fungal Proteins / metabolism
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Histidine Kinase
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MAP Kinase Kinase Kinases / metabolism
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Mitogen-Activated Protein Kinases / drug effects
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Mitogen-Activated Protein Kinases / metabolism*
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Molecular Sequence Data
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Mutation
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Peroxides / pharmacology*
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Phosphorylation
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Protein Kinases / genetics
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Protein Kinases / metabolism
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Schizosaccharomyces / drug effects*
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Schizosaccharomyces / metabolism*
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Schizosaccharomyces pombe Proteins*
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Transcription Factors / genetics
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Transcription Factors / metabolism
Substances
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Activating Transcription Factor 1
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Basic-Leucine Zipper Transcription Factors
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Cell Cycle Proteins
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DNA-Binding Proteins
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Free Radicals
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Fungal Proteins
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Mcs4 protein, S pombe
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PALF protein, Emericella nidulans
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Pap1 protein, S pombe
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Peroxides
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Schizosaccharomyces pombe Proteins
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Transcription Factors
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Protein Kinases
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Mitogen-Activated Protein Kinases
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sty1 protein, S pombe
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MAP Kinase Kinase Kinases
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wis4 protein, S pombe
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Histidine Kinase