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

V Buck1, J Quinn, T Soto Pino

  • 1Division of Yeast Genetics, National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA United Kingdom.

Insights

Fission yeast utilize distinct phospho-relay pathways to manage free radical stress. Mak2p/Mak3p histidine kinases activate Sty1p, while Mak1p influences Pap1p/Prr1p pathways for robust defense.

Area of Science:

  • Cellular stress response mechanisms
  • Signal transduction pathways in yeast

Background:

  • The Sty1p/Spc1p MAP kinase pathway in Schizosaccharomyces pombe regulates gene expression via Atf1p and Pap1p transcription factors.
  • Mcs4p, a response regulator, functions upstream of Sty1p, interacting with Wak1p/Wis4p MAP kinase kinase kinase.

Purpose of the Study:

  • To investigate the role of Mcs4p phosphorylation in Sty1p activation during peroxide stress.
  • To elucidate the involvement of histidine kinases Mak2p, Mak3p, and Mak1p in fission yeast stress response pathways.

Main Methods:

  • Phosphorylation analysis of Mcs4p.
  • Genetic analysis of histidine kinase mutants (Mak2p, Mak3p, Mak1p) and their impact on Sty1p, Atf1p, Pap1p, and Prr1p activity.
  • Assessment of cellular sensitivity to peroxide stress.

Main Results:

  • Mcs4p phosphorylation on a specific aspartic acid residue is crucial for Sty1p activation solely under peroxide stress.
  • Mak2p and Mak3p initiate a phospho-relay system essential for Sty1p activation and Atf1p-dependent gene expression.
  • Cells lacking Mak2p or Mak3p exhibit peroxide sensitivity, particularly in the absence of Prr1p.
  • Mak1p, while not regulating Sty1p/Atf1p, partially contributes to Pap1p/Prr1p-dependent transcription.

Conclusions:

  • The transcriptional response to free radical attack in fission yeast is orchestrated by at least two independent phospho-relay pathways.
  • Distinct histidine kinase pathways differentially regulate transcription factors involved in oxidative stress defense.