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

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• dc.contributor.author Calvo, Isabel A.ca
• dc.contributor.author Ayté del Olmo, Joséca
• dc.contributor.author Hidalgo Hernando, Elenaca
• dc.date.accessioned 2015-12-02T15:07:29Z
• dc.date.available 2015-12-02T15:07:29Z
• dc.date.issued 2013
• 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.ca
• 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/pdfca
• 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.124370ca
• dc.identifier.doi http://dx.doi.org/10.1242/jcs.124370
• dc.identifier.issn 0021-9533
• dc.identifier.uri http://hdl.handle.net/10230/25312
• dc.language.iso engca
• dc.publisher Company of Biologistsca
• dc.relation.ispartof Journal of cell science. 2013;126(Pt 10):2279-84
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2009-06933
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2012-32045
• dc.rights © Company of Biologists http://jcs.biologists.org/content/126/10/2279.long DOI 10.1242/jcs.124370ca
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• 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.subject.other Regulació genèticaca
• dc.subject.other Schizosaccharomyces pombe -- Metabolismeca
• dc.subject.other Proteïnes Rasca
• dc.title Reversible thiol oxidation in the H2O2-dependent activation of the transcription factor Pap1ca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/publishedVersionca