Peroxide sensors for the fission yeast stress-activated mitogen-activated protein kinase pathway

Mol Biol Cell. 2001 Feb;12(2):407-19. doi: 10.1091/mbc.12.2.407.


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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 1
  • Amino Acid Sequence
  • Base Sequence
  • Basic-Leucine Zipper Transcription Factors
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • DNA-Binding Proteins / metabolism
  • Enzyme Activation / drug effects
  • Free Radicals / metabolism
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Histidine Kinase
  • MAP Kinase Kinase Kinases / metabolism
  • Mitogen-Activated Protein Kinases / drug effects
  • Mitogen-Activated Protein Kinases / metabolism*
  • Molecular Sequence Data
  • Mutation
  • Peroxides / pharmacology*
  • Phosphorylation
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Schizosaccharomyces / drug effects*
  • Schizosaccharomyces / metabolism*
  • Schizosaccharomyces pombe Proteins*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • Activating Transcription Factor 1
  • Basic-Leucine Zipper Transcription Factors
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Free Radicals
  • Fungal Proteins
  • Mcs4 protein, S pombe
  • PALF protein, Emericella nidulans
  • Pap1 protein, S pombe
  • Peroxides
  • Schizosaccharomyces pombe Proteins
  • Transcription Factors
  • Protein Kinases
  • Mitogen-Activated Protein Kinases
  • sty1 protein, S pombe
  • MAP Kinase Kinase Kinases
  • wis4 protein, S pombe
  • Histidine Kinase