Peroxide sensors for the fission yeast stress-activated mitogen-activated protein kinase pathway.
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.
Buck
V
V
Division of Yeast Genetics, National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA United Kingdom.
Quinn
J
J
Soto Pino
T
T
Martin
H
H
Saldanha
J
J
Makino
K
K
Morgan
B A
BA
Millar
J B
JB
D051697:Activating Transcription Factor 1; D000595:Amino Acid Sequence; D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005609:Free Radicals / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D000071677:Histidine Kinase; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D010545:Peroxides / Q000494:pharmacology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000187:drug effects* / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D051697:Activating Transcription Factor 1; D050976:Basic-Leucine Zipper Transcription Factors; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005609:Free Radicals; D005656:Fungal Proteins; C105788:Mcs4 protein, S pombe; C107929:PALF protein, Emericella nidulans; C105096:Pap1 protein, S pombe; D010545:Peroxides; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; D011494:Protein Kinases; D020928:Mitogen-Activated Protein Kinases; C095409:sty1 protein, S pombe; D020930:MAP Kinase Kinase Kinases; C109169:wis4 protein, S pombe; D000071677:Histidine Kinase