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

Lookup NU author(s): Professor Janet Quinn, Professor Brian Morgan

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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 Maklp histidine kinase, which also contains PAS/PAC repeats, does not regulate Stylp 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 metadata

Author(s): Buck V, Quinn J, Pino TS, Martin H, Saldanha J, Makino K, Morgan BA, Millar JBA

Publication type: Article

Publication status: Published

Journal: Molecular Biology of the Cell

Year: 2001

Volume: 12

Issue: 2

Pages: 407-419

Print publication date: 01/01/2001

ISSN (print): 1059-1524

ISSN (electronic): 1939-4586

Publisher: American Society for Cell Biology

PubMed id: 11179424


Funding

Funder referenceFunder name
MC_U117531948Medical Research Council

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