title: Multiple pathways differentially regulate global oxidative stress responses in fission yeast.
abstract: Cellular protection against oxidative damage is relevant to ageing and numerous diseases. We analyzed the diversity of genome-wide gene expression programs and their regulation in response to various types and doses of oxidants in Schizosaccharomyces pombe. A small core gene set, regulated by the AP-1-like factor Pap1p and the two-component regulator Prr1p, was universally induced irrespective of oxidant and dose. Strong oxidative stresses led to a much larger transcriptional response. The mitogen-activated protein kinase (MAPK) Sty1p and the bZIP factor Atf1p were critical for the response to hydrogen peroxide. A newly identified zinc-finger protein, Hsr1p, is uniquely regulated by all three major regulatory systems (Sty1p-Atf1p, Pap1p, and Prr1p) and in turn globally supports gene expression in response to hydrogen peroxide. Although the overall transcriptional responses to hydrogen peroxide and t-butylhydroperoxide were similar, to our surprise, Sty1p and Atf1p were less critical for the response to the latter. Instead, another MAPK, Pmk1p, was involved in surviving this stress, although Pmk1p played only a minor role in regulating the transcriptional response. These data reveal a considerable plasticity and differential control of regulatory pathways in distinct oxidative stress conditions, providing both specificity and backup for protection from oxidative damage.
authors.affiliation: Cancer Research UK Fission Yeast Functional Genomics Group, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, United Kingdom.
authors.forename: Dongrong
authors.initials: D
authors.lastname: Chen
authors.forename: Caroline R M
authors.initials: CR
authors.lastname: Wilkinson
authors.forename: Stephen
authors.initials: S
authors.lastname: Watt
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Penkett
authors.forename: W Mark
authors.initials: WM
authors.lastname: Toone
authors.forename: Nic
authors.initials: N
authors.lastname: Jones
authors.forename: Jürg
authors.initials: J
authors.lastname: Bähler
mesh_terms: D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D005800:Genes, Fungal; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics*; D012568:Schizosaccharomyces / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*; D024483:Vitamin K 3 / Q000494:pharmacology; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
chemical_list: D016877:Oxidants; D029702:Schizosaccharomyces pombe Proteins; D024483:Vitamin K 3; D020122:tert-Butylhydroperoxide; D006861:Hydrogen Peroxide; D020929:Mitogen-Activated Protein Kinase Kinases