A Cysteine-sulfinic Acid in Peroxiredoxin Regulates H2O2-sensing by the Antioxidant Pap1 Pathway

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2005 Jun 16

PMID 15956211

Citations 103

Authors

Ana P Vivancos

Esther A Castillo

Benoit Biteau

Carine Nicot

Jose Ayte

Michel B Toledano

Elena Hidalgo

Affiliations

Soon will be listed here.

Abstract

The Schizosaccharomyces pombe transcription factor Pap1 regulates antioxidant-gene transcription in response to H2O2. Pap1 activation occurs only at low, but not elevated, H2O2 concentrations that instead strongly trigger the mitogen-activated protein kinase Sty1 pathway. Here, we identify the peroxiredoxin Tpx1 as the upstream activator of Pap1. We show that, at low H2O2 concentrations, this oxidant scavenger can transfer a redox signal to Pap1, whereas higher concentrations of the oxidant inhibit the Tpx1-Pap1 redox relay through the temporal inactivation of Tpx1 by oxidation of its catalytic cysteine to a sulfinic acid. This cysteine modification can be reversed by the sulfiredoxin Srx1, its expression in response to high doses of H2O2 strictly depending on active Sty1. Thus, Tpx1 oxidation to the cysteine-sulfinic acid and its reversion by Srx1 constitutes a previously uncharacterized redox switch in H2O2 signaling, restricting Pap1 activation within a narrow range of H2O2 concentrations.

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References

Ikner A, Shiozaki K . Yeast signaling pathways in the oxidative stress response. Mutat Res. 2004; 569(1-2):13-27. DOI: 10.1016/j.mrfmmm.2004.09.006. View

Chang T, Jeong W, Woo H, Lee S, Park S, Rhee S . Characterization of mammalian sulfiredoxin and its reactivation of hyperoxidized peroxiredoxin through reduction of cysteine sulfinic acid in the active site to cysteine. J Biol Chem. 2004; 279(49):50994-1001. DOI: 10.1074/jbc.M409482200. View

Shiozaki K, Russell P . Cell-cycle control linked to extracellular environment by MAP kinase pathway in fission yeast. Nature. 1995; 378(6558):739-43. DOI: 10.1038/378739a0. View

Biteau B, Labarre J, Toledano M . ATP-dependent reduction of cysteine-sulphinic acid by S. cerevisiae sulphiredoxin. Nature. 2003; 425(6961):980-4. DOI: 10.1038/nature02075. View

Budanov A, Sablina A, Feinstein E, Koonin E, Chumakov P . Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpD. Science. 2004; 304(5670):596-600. DOI: 10.1126/science.1095569. View

Vivancos A, Castillo E, Jones N, Ayte J, Hidalgo E . Activation of the redox sensor Pap1 by hydrogen peroxide requires modulation of the intracellular oxidant concentration. Mol Microbiol. 2004; 52(5):1427-35. DOI: 10.1111/j.1365-2958.2004.04065.x. View

Veal E, Findlay V, Day A, Bozonet S, Evans J, Quinn J . A 2-Cys peroxiredoxin regulates peroxide-induced oxidation and activation of a stress-activated MAP kinase. Mol Cell. 2004; 15(1):129-39. DOI: 10.1016/j.molcel.2004.06.021. View

Toledano M, Delaunay A, Monceau L, Tacnet F . Microbial H2O2 sensors as archetypical redox signaling modules. Trends Biochem Sci. 2004; 29(7):351-7. DOI: 10.1016/j.tibs.2004.05.005. View

Toda T, Shimanuki M, Yanagida M . 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. 1991; 5(1):60-73. DOI: 10.1101/gad.5.1.60. View

10.

Moreno S, Klar A, Nurse P . Molecular genetic analysis of fission yeast Schizosaccharomyces pombe. Methods Enzymol. 1991; 194:795-823. DOI: 10.1016/0076-6879(91)94059-l. View

11.

Maundrell K . Thiamine-repressible expression vectors pREP and pRIP for fission yeast. Gene. 1993; 123(1):127-30. DOI: 10.1016/0378-1119(93)90551-d. View

12.

Keeney J, Boeke J . Efficient targeted integration at leu1-32 and ura4-294 in Schizosaccharomyces pombe. Genetics. 1994; 136(3):849-56. PMC: 1205890. DOI: 10.1093/genetics/136.3.849. View

13.

Millar J, Buck V, Wilkinson M . Pyp1 and Pyp2 PTPases dephosphorylate an osmosensing MAP kinase controlling cell size at division in fission yeast. Genes Dev. 1995; 9(17):2117-30. DOI: 10.1101/gad.9.17.2117. View

14.

Maillet I, Lagniel G, Perrot M, Boucherie H, LABARRE J . Rapid identification of yeast proteins on two-dimensional gels. J Biol Chem. 1996; 271(17):10263-70. DOI: 10.1074/jbc.271.17.10263. View

15.

Degols G, Shiozaki K, Russell P . Activation and regulation of the Spc1 stress-activated protein kinase in Schizosaccharomyces pombe. Mol Cell Biol. 1996; 16(6):2870-7. PMC: 231280. DOI: 10.1128/MCB.16.6.2870. View

16.

Shiozaki K, Russell P . Conjugation, meiosis, and the osmotic stress response are regulated by Spc1 kinase through Atf1 transcription factor in fission yeast. Genes Dev. 1996; 10(18):2276-88. DOI: 10.1101/gad.10.18.2276. View

17.

Nakagawa C, Yamada K, Mutoh N . Role of Atf1 and Pap1 in the induction of the catalase gene of fission yeast schizosaccharomyces pombe. J Biochem. 2000; 127(2):233-8. DOI: 10.1093/oxfordjournals.jbchem.a022599. View

18.

Koo K, Lee S, Jeong S, Kim E, Kim H, Kim K . Regulation of thioredoxin peroxidase activity by C-terminal truncation. Arch Biochem Biophys. 2002; 397(2):312-8. DOI: 10.1006/abbi.2001.2700. View

19.

Wood V, Gwilliam R, Rajandream M, LYNE M, Lyne R, Stewart A . The genome sequence of Schizosaccharomyces pombe. Nature. 2002; 415(6874):871-80. DOI: 10.1038/nature724. View

20.

Quinn J, Findlay V, Dawson K, Millar J, Jones N, Morgan B . Distinct regulatory proteins control the graded transcriptional response to increasing H(2)O(2) levels in fission yeast Schizosaccharomyces pombe. Mol Biol Cell. 2002; 13(3):805-16. PMC: 99600. DOI: 10.1091/mbc.01-06-0288. View