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Reversible thiol oxidation in the H2O2-dependent activation of the transcription factor Pap1

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dc.contributor.author Calvo, Isabel A.
dc.contributor.author Ayté del Olmo, José
dc.contributor.author Hidalgo Hernando, Elena
dc.date.accessioned 2015-12-02T15:07:29Z
dc.date.available 2015-12-02T15:07:29Z
dc.date.issued 2013
dc.identifier.citation Calvo IA, Ayté J, Hidalgo E. Reversible thiol oxidation in the H2O2-dependent activation of the transcription factor Pap1. Journal of cell science. 2013;126(Pt 10):2279-84. DOI: 10.1242/jcs.124370
dc.identifier.issn 0021-9533
dc.identifier.uri http://hdl.handle.net/10230/25312
dc.description.abstract Reversible thiol oxidation is both a mark of hydrogen peroxide (H2O2) toxicity and an initiator of signalling events. H2O2 sensors contain exposed and reactive cysteine residues, which become transiently oxidized as an activation mechanism. In fission yeast, the Pap1 (pombe AP-1) transcription factor is normally cytosolic, and upon H2O2 stress it undergoes post-translational modifications impairing its nuclear export; genetic evidences suggested the formation of a disulphide bond in Pap1 as a triggering activation event. Nuclear Pap1 is then recruited to about 50-80 promoters and induces an adaptation response. We have now dissected the role of all seven cysteine residues in Pap1 using genetic and proteomic techniques, and we show that four of them are required for Pap1 to be activated by H2O2 stress. Thus, mutants lacking each one of these cysteine residues display sensitivity to peroxides. Furthermore, these mutant proteins do not become oxidized by H2O2 and cannot bind to promoters or trigger the Pap1-dependent gene expression program. We also demonstrate, by proteomic analysis of reduced and oxidized Pap1, that these four cysteine residues are reversibly oxidized upon H2O2 stress. Our study suggests that not just one but probably two disulphide bonds are required to promote the important conformational changes that trigger Pap1 activation and nuclear accumulation.
dc.description.sponsorship This work was supported by the Spanish Ministry of Science and Innovation, PLAN E and FEDER [grant numbers BFU2009-06933, BFU2012-32045 to E.H.]; the Spanish program Consolider-Ingenio 2010 [grant number CSD 2007-0020 to E.H.]; the Generalitat de Catalunya (Spain) [grant number SGR2009-196 to E.H.]; andInstitució Catalana de Recerca i Estudis Avançats Academia Awards (Generalitat de Catalunya) to E.H. and J.A.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Company of Biologists
dc.relation.ispartof Journal of cell science. 2013;126(Pt 10):2279-84
dc.rights © Company of Biologists http://jcs.biologists.org/content/126/10/2279.long DOI 10.1242/jcs.124370
dc.subject.other Regulació genètica
dc.subject.other Schizosaccharomyces pombe -- Metabolisme
dc.subject.other Proteïnes Ras
dc.title Reversible thiol oxidation in the H2O2-dependent activation of the transcription factor Pap1
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1242/jcs.124370
dc.subject.keyword Disulphide bond
dc.subject.keyword Fission yeast
dc.subject.keyword H2O2 sensor
dc.subject.keyword Pap1
dc.subject.keyword Redox cascade
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2009-06933
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2012-32045
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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