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Oxidative stress in Schizosaccharomyces pombe: different H2O2 levels, different response pathways

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Abstract

Schizosaccharomyces pombe triggers different signalling pathways depending on the severity of the oxidative stress exerted, the main ones being the Pap1 and the Sty1 pathways. The Pap1 transcription factor is more sensitive to hydrogen peroxide (H2O2) than the MAP kinase Sty1 pathway, and is designed to induce adaptation, rather than survival, responses. The peroxiredoxin Tpx1 acts as a H2O2 sensor and the upstream activator of the Pap1 pathway. Therefore, sensitivity to H2O2 depends on this thioredoxin peroxidase. In order to achieve maximal activation of the MAP kinase pathway, the concentration of H2O2 needs to be at least fivefold higher than that to fully activate Pap1. Tpx1 is a H2O2 scavenger, thus its peroxidase activity is essential for aerobic growth. As described for other eukaryotic peroxiredoxins, high doses of H2O2 temporarily inactivate Tpx1 and delay Pap1 activation, whereas the Sty1 pathway remains fully functional under these conditions. As part of the Sty1-dependent transcriptional response, the expression of Srx1 is induced and this reductase re-activates the over-oxidised Tpx1. Therefore, the antioxidant pathways of the fission yeast are perfectly designed so that the transcriptional programs triggered by the different signalling pathways never overlap.

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References

  • Aoyama K, Mitsubayashi Y, Aiba H, Mizuno T (2000) Spy1, a histidine-containing phosphotransfer signaling protein, regulates the fission yeast cell cycle through the Mcs4 response regulator. J Bacteriol 182:4868–4874

    Article  PubMed  CAS  Google Scholar 

  • Aoyama K, Aiba H, Mizuno T (2001) Genetic analysis of the His-to-Asp phosphorelay implicated in mitotic cell cycle control: involvement of histidine-kinase genes of Schizosaccharomyces pombe. Biosci Biotechnol Biochem 65:2347–2352

    Article  PubMed  CAS  Google Scholar 

  • Asp E, Sunnerhagen P (2003) Mkp1 and Mkp2, two MAPKAP-kinase homologues in Schizosaccharomyces pombe, interact with the MAP kinase Sty1. Mol Genet Genomics 268:585–597

    PubMed  CAS  Google Scholar 

  • Biteau B, Labarre J, Toledano MB (2003) ATP-dependent reduction of cysteine–sulphinic acid by S. cerevisiae sulphiredoxin. Nature 425:980–984

    Article  PubMed  CAS  Google Scholar 

  • Bozonet SM, Findlay VJ, Day AM, Cameron J, Veal EA, Morgan BA (2005) Oxidation of a eukaryotic 2-Cys peroxiredoxin is a molecular switch controlling the transcriptional response to increasing levels of hydrogen peroxide. J Biol Chem 280:23319–23327

    Article  PubMed  CAS  Google Scholar 

  • Buck V et al (2001) Peroxide sensors for the fission yeast stress-activated mitogen-activated protein kinase pathway. Mol Biol Cell 12:407–419

    PubMed  CAS  Google Scholar 

  • Budanov AV, Sablina AA, Feinstein E, Koonin EV, Chumakov PM (2004) Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpD. Science 304:596–600

    Article  PubMed  CAS  Google Scholar 

  • Casso D, Beach D (1996) A mutation in a thioredoxin reductase homolog suppresses p53-induced growth inhibition in the fission yeast Schizosaccharomyces pombe. Mol Gen Genet 252:518–529

    PubMed  CAS  Google Scholar 

  • Castillo EA et al (2002) Diethylmaleate activates the transcription factor Pap1 by covalent modification of critical cysteine residues. Mol Microbiol 45:243–254

    Article  PubMed  CAS  Google Scholar 

  • Castillo EA, Vivancos AP, Hidalgo E (2003a) Pap1, a sensor of oxidative stress in Schizosaccharomyces pombe. In: Pandalai SG (ed) Recent developments in cell research. Research Signpost, Trivandrum, pp 217–230

    Google Scholar 

  • Castillo EA, Vivancos AP, Jones N, Ayte J, Hidalgo E (2003b) Schizosaccharomyces pombe cells lacking the Ran-binding protein Hba1 show a multidrug resistance phenotype due to constitutive nuclear accumulation of Pap1. J Biol Chem 278:40565–40572

    Article  CAS  Google Scholar 

  • Chen D et al (2003) Global transcriptional responses of fission yeast to environmental stress. Mol Biol Cell 14:214–229

    Article  PubMed  CAS  Google Scholar 

  • Chuang MH, Wu MS, Lo WL, Lin JT, Wong CH, Chiou SH (2006) The antioxidant protein alkylhydroperoxide reductase of Helicobacter pylori switches from a peroxide reductase to a molecular chaperone function. Proc Natl Acad Sci USA 103:2552–2557

    Article  PubMed  CAS  Google Scholar 

  • Degols G, Russell P (1997) Discrete roles of the Spc1 kinase and the Atf1 transcription factor in the UV response of Schizosaccharomyces pombe. Mol Cell Biol 17:3356–3363

    PubMed  CAS  Google Scholar 

  • Degols G, Shiozaki K, Russell P (1996) Activation and regulation of the Spc1 stress-activated protein kinase in Schizosaccharomyces pombe. Mol Cell Biol 16:2870–2877

    PubMed  CAS  Google Scholar 

  • Delaunay A, Isnard AD, Toledano MB (2000) H(2)O(2) sensing through oxidation of the Yap1 transcription factor. EMBO J 19:5157–5166

    Article  PubMed  CAS  Google Scholar 

  • Delaunay A, Pflieger D, Barrault MB, Vinh J, Toledano MB (2002) A thiol peroxidase is an h(2)o(2) receptor and redox-transducer in gene activation. Cell 111:471–481

    Article  PubMed  CAS  Google Scholar 

  • Gaits F, Russell P (1999) Active nucleocytoplasmic shuttling required for function and regulation of stress-activated kinase Spc1/StyI in fission yeast. Mol Biol Cell 10:1395–1407

    PubMed  CAS  Google Scholar 

  • Gaits F, Degols G, Shiozaki K, Russell P (1998) Phosphorylation and association with the transcription factor Atf1 regulate localization of Spc1/Sty1 stress-activated kinase in fission yeast [see comments]. Genes Dev. 12:1464–1473

    PubMed  CAS  Google Scholar 

  • Greenall A et al (2002) Role of fission yeast Tup1-like repressors and Prr1 transcription factor in response to salt stress. Mol Biol Cell 13:2977–2989

    Article  PubMed  CAS  Google Scholar 

  • Ikner A, Shiozaki K (2005) Yeast signaling pathways in the oxidative stress response. Mutat Res 569:13–27

    PubMed  CAS  Google Scholar 

  • Jang HH et al (2004) Two enzymes in one; two yeast peroxiredoxins display oxidative stress-dependent switching from a peroxidase to a molecular chaperone function. Cell 117:625–635

    Article  PubMed  CAS  Google Scholar 

  • Kanoh J, Watanabe Y, Ohsugi M, Iino Y, Yamamoto M (1996) Schizosaccharomyces pombe gad7+ encodes a phosphoprotein with a bZIP domain, which is required for proper G1 arrest and gene expression under nitrogen starvation. Genes Cells 1:391–408

    Article  PubMed  CAS  Google Scholar 

  • Kon N, Schroeder SC, Krawchuk MD, Wahls WP (1998) Regulation of the Mts1–Mts2-dependent ade6-M26 meiotic recombination hot spot and developmental decisions by the Spc1 mitogen-activated protein kinase of fission yeast. Mol Cell Biol 18:7575–7583

    PubMed  CAS  Google Scholar 

  • Kudo N, Taoka H, Toda T, Yoshida M, Horinouchi S (1999) A novel nuclear export signal sensitive to oxidative stress in the fission yeast transcription factor Pap1. J Biol Chem 274:15151–15158

    Article  PubMed  CAS  Google Scholar 

  • Kumada K, Yanagida M, Toda T (1996) Caffeine-resistance in fission yeast is caused by mutations in a single essential gene, crm1+. Mol Gen Genet 250:59–68

    PubMed  CAS  Google Scholar 

  • Lee J, Dawes IW, Roe JH (1997) Isolation, expression, and regulation of the pgr1(+) gene encoding glutathione reductase absolutely required for the growth of Schizosaccharomyces pombe. J Biol Chem 272:23042–23049

    Article  PubMed  CAS  Google Scholar 

  • Lopez-Aviles S et al (2005) Inactivation of the Cdc25 phosphatase by the stress-activated Srk1 kinase in fission yeast. Mol Cell 17:49–59

    Article  PubMed  CAS  Google Scholar 

  • Madrid M et al (2004) A cooperative role for Atf1 and Pap1 in the detoxification of the oxidative stress induced by glucose deprivation in Schizosaccharomyces pombe. J Biol Chem 279:41594–41602

    Article  PubMed  CAS  Google Scholar 

  • Millar JB, Buck V, Wilkinson MG (1995) Pyp1 and Pyp2 PTPases dephosphorylate an osmosensing MAP kinase controlling cell size at division in fission yeast. Genes Dev 9:2117–2130

    PubMed  CAS  Google Scholar 

  • Morgan BA, Banks GR, Toone WM, Raitt D, Kuge S, Johnston LH (1997) The Skn7 response regulator controls gene expression in the oxidative stress response of the budding yeast Saccharomyces cerevisiae. EMBO J 16:1035–1044

    Article  PubMed  CAS  Google Scholar 

  • Nakagawa CW, Mutoh N, Hayashi Y (1995) Transcriptional regulation of catalase gene in the fission yeast Schizosaccharomyces pombe: molecular cloning of the catalase gene and northern blot analyses of the transcript. J Biochem (Tokyo) 118:109–116

    CAS  Google Scholar 

  • Nakamichi N, Yamada H, Aoyama K, Ohmiya R, Aiba H, Mizuno T (2002) His-to-Asp phosphorelay circuitry for regulation of sexual development in Schizosaccharomyces pombe. Biosci Biotechnol Biochem 66:2663–2672

    Article  PubMed  CAS  Google Scholar 

  • Nakamichi N, Yanada H, Aiba H, Aoyama K, Ohmiya R, Mizuno T (2003) Characterization of the Prr1 response regulator with special reference to sexual development in Schizosaccharomyces pombe. Biosci Biotechnol Biochem 67:547–555

    Article  PubMed  CAS  Google Scholar 

  • Nguyen AN, Shiozaki K (1999) Heat-shock-induced activation of stress MAP kinase is regulated by threonine- and tyrosine-specific phosphatases. Genes Dev 13:1653–1663

    PubMed  CAS  Google Scholar 

  • Nguyen AN, Lee A, Place W, Shiozaki K (2000) Multistep phosphorelay proteins transmit oxidative stress signals to the fission yeast stress-activated protein kinase. Mol Biol Cell 11:1169–1181

    PubMed  CAS  Google Scholar 

  • Ohmiya R, Kato C, Yamada H, Aiba H, Mizuno T (1999) A fission yeast gene (prr1(+)) that encodes a response regulator implicated in oxidative stress response. J Biochem (Tokyo) 125:1061–1066

    CAS  Google Scholar 

  • Ohmiya R, Yamada H, Kato C, Aiba H, Mizuno T (2000) The Prr1 response regulator is essential for transcription of ste11+ and for sexual development in fission yeast. Mol Gen Genet 264:441–451

    Article  PubMed  CAS  Google Scholar 

  • Okazaki S, Naganuma A, Kuge S (2005) Peroxiredoxin-mediated redox regulation of the nuclear localization of Yap1, a transcription factor in budding yeast. Antioxid Redox Signal 7:327–334

    Article  PubMed  CAS  Google Scholar 

  • O’Rourke SM, Herskowitz I, O’Shea EK (2002) Yeast go the whole HOG for the hyperosmotic response. Trends Genet 18:405–412

    Article  PubMed  CAS  Google Scholar 

  • Quinn J et al (2002) Distinct regulatory proteins control the graded transcriptional response to increasing H(2)O(2) levels in fission yeast schizosaccharomyces pombe. Mol Biol Cell 13:805–816

    Article  PubMed  CAS  Google Scholar 

  • Rhee SG, Kang SW, Netto LE, Seo MS, Stadtman ER (1999) A family of novel peroxidases, peroxiredoxins. Biofactors 10:207–209

    PubMed  CAS  Google Scholar 

  • Rhee SG, Chae HZ, Kim K (2005) Peroxiredoxins: a historical overview and speculative preview of novel mechanisms and emerging concepts in cell signaling. Free Radic Biol Med 38:1543–1552

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez-Gabriel MA, Russell P (2005) Distinct signaling pathways respond to arsenite and reactive oxygen species in Schizosaccharomyces pombe. Eukaryot Cell 4:1396–1402

    Article  PubMed  CAS  Google Scholar 

  • Samejima I, Mackie S, Fantes PA (1997) Multiple modes of activation of the stress-responsive MAP kinase pathway in fission yeast. EMBO J 16:6162–6170

    Article  PubMed  CAS  Google Scholar 

  • Sanchez-Piris M et al (2002) The serine/threonine kinase Cmk2 is required for oxidative stress response in fission yeast. J Biol Chem 277:17722–17727

    Article  PubMed  CAS  Google Scholar 

  • Shieh JC, Wilkinson MG, Buck V, Morgan BA, Makino K, Millar JB (1997) The Mcs4 response regulator coordinately controls the stress-activated Wak1-Wis1-Sty1 MAP kinase pathway and fission yeast cell cycle. Genes Dev 11:1008–1022

    PubMed  CAS  Google Scholar 

  • Shiozaki K, Russell P (1995) Cell-cycle control linked to extracellular environment by MAP kinase pathway in fission yeast. Nature 378:739–743

    Article  PubMed  CAS  Google Scholar 

  • Shiozaki K, Russell P (1996) Conjugation, meiosis, and the osmotic stress response are regulated by Spc1 kinase through Atf1 transcription factor in fission yeast. Genes Dev 10:2276–2288

    PubMed  CAS  Google Scholar 

  • Shiozaki K, Shiozaki M, Russell P (1997) Mcs4 mitotic catastrophe suppressor regulates the fission yeast cell cycle through the Wik1-Wis1-Spc1 kinase cascade. Mol Biol Cell 8:409–419

    PubMed  CAS  Google Scholar 

  • Smith DA et al (2002) The Srk1 protein kinase is a target for the Sty1 stress-activated MAPK in fission yeast. J Biol Chem 277:33411–33421

    Article  PubMed  CAS  Google Scholar 

  • Soto T et al (2002) Cold induces stress-activated protein kinase-mediated response in the fission yeast Schizosaccharomyces pombe. Eur J Biochem 269:5056–5065

    Article  PubMed  CAS  Google Scholar 

  • Takeda T, Toda T, Kominami K, Kohnosu A, Yanagida M, Jones N (1995) Schizosaccharomyces pombe atf1+ encodes a transcription factor required for sexual development and entry into stationary phase. EMBO J 14:6193–6208

    PubMed  CAS  Google Scholar 

  • Toda T, Shimanuki M, Yanagida M (1991) Fission yeast genes that confer resistance to staurosporine encode an AP-1-like transcription factor and a protein kinase related to the mammalian ERK1/MAP2 and budding yeast FUS3 and KSS1 kinases. Genes Dev 5:60–73

    PubMed  CAS  Google Scholar 

  • Toone WM, Kuge S, Samuels M, Morgan BA, Toda T, Jones N (1998) Regulation of the fission yeast transcription factor Pap1 by oxidative stress: requirement for the nuclear export factor Crm1 (Exportin) and the stress-activated MAP kinase Sty1/Spc1 [published erratum appears in Genes Dev 1998 Aug 15;12(16):2650] [see comments]. Genes Dev 12:1453–1463

    Google Scholar 

  • Turi TG, Webster P, Rose JK (1994) Brefeldin A sensitivity and resistance in Schizosaccharomyces pombe. Isolation of multiple genes conferring resistance. J Biol Chem 269:24229–24236

    PubMed  CAS  Google Scholar 

  • Veal EA et al (2004) A 2-Cys peroxiredoxin regulates peroxide-induced oxidation and activation of a stress-activated MAP Kinase. Mol Cell 15:129–139

    Article  PubMed  CAS  Google Scholar 

  • Veal EA, Ross SJ, Malakasi P, Peacock E, Morgan BA (2003) Ybp1 is required for the hydrogen peroxide-induced oxidation of the Yap1 transcription factor. J Biol Chem 278:30896–30904

    Article  PubMed  CAS  Google Scholar 

  • Vivancos AP et al (2005) A cysteine-sulfinic acid in peroxiredoxin regulates H2O2-sensing by the antioxidant Pap1 pathway. Proc Natl Acad Sci USA 102:8875–8880

    Article  PubMed  CAS  Google Scholar 

  • Vivancos AP, Castillo EA, Jones N, Ayte J, Hidalgo E (2004) Activation of the redox sensor Pap1 by hydrogen peroxide requires modulation of the intracellular oxidant concentration. Mol Microbiol 52:1427–1435

    Article  PubMed  CAS  Google Scholar 

  • Wahls WP, Smith GR (1994) A heteromeric protein that binds to a meiotic homologous recombination hot spot: correlation of binding and hot spot activity. Genes Dev 8:1693–1702

    PubMed  CAS  Google Scholar 

  • Wang LY, Shimada K, Morishita M, Shiozaki K (2005) Response of fission yeast to toxic cations involves cooperative action of the stress-activated protein kinase Spc1/Sty1 and the Hal4 protein kinase. Mol Cell Biol 25:3945–3955

    Article  PubMed  CAS  Google Scholar 

  • Wilkinson MG et al (1996) The Atf1 transcription factor is a target for the Sty1 stress-activated MAP kinase pathway in fission yeast. Genes Dev 10:2289–2301

    PubMed  CAS  Google Scholar 

  • Woo HA, Kang SW, Kim HK, Yang KS, Chae HZ, Rhee SG (2003) Reversible oxidation of the active site cysteine of peroxiredoxins to cysteine sulfinic acid. Immunoblot detection with antibodies specific for the hyperoxidized cysteine-containing sequence. J Biol Chem 278:47361–47364

    Article  PubMed  CAS  Google Scholar 

  • Wood ZA, Poole LB, Karplus PA (2003a) Peroxiredoxin evolution and the regulation of hydrogen peroxide signaling. Science 300:650–653

    Article  CAS  Google Scholar 

  • Wood ZA, Schroder E, Robin Harris J, Poole LB (2003b) Structure, mechanism and regulation of peroxiredoxins. Trends Biochem Sci 28:32–40

    Article  CAS  Google Scholar 

  • Yang KS et al (2002) Inactivation of human peroxiredoxin I during catalysis as the result of the oxidation of the catalytic site cysteine to cysteine–sulfinic acid. J Biol Chem 277:38029–38036

    Article  PubMed  CAS  Google Scholar 

  • Zheng M, Storz G (2000) Redox sensing by prokaryotic transcription factors. Biochem Pharmacol 59:1–6

    Article  PubMed  CAS  Google Scholar 

  • Zuin A et al (2005) The glycolytic metabolite methylglyoxal activates Pap1 and Sty1 stress responses in Schizosaccharomyces pombe. J Biol Chem 280:36708–36713

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

A. P.V and M. S. are recipients of predoctoral fellowships from the Ministerio de Ciencia y Tecnología of Spain, and A. Z is the recipient of a predoctoral fellowship from Generalitat de Catalunya. This work was supported by Dirección General de Investigación, Spanish grants BMC2003-00220 and BFU2006-02610, and “Distinció de la Generalitat de Catalunya per a la Promoció de la Recerca Universitaria. Joves Investigadors” DURSI (Generalitat de Catalunya) to E. H.

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  1. Cell Signalling Unit, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, C/Dr. Aiguader 80, Barcelona, 08003, Spain

    Ana P. Vivancos, Mónica Jara, Alice Zuin, Miriam Sansó & Elena Hidalgo

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  1. Ana P. Vivancos
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  2. Mónica Jara
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  3. Alice Zuin
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Correspondence to Elena Hidalgo.

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Communicated by T. Nyström.

Ana P. Vivancos and Mónica Jara contributed equally to this work.

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Vivancos, A.P., Jara, M., Zuin, A. et al. Oxidative stress in Schizosaccharomyces pombe: different H2O2 levels, different response pathways. Mol Genet Genomics 276, 495–502 (2006). https://doi.org/10.1007/s00438-006-0175-z

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