Physical interaction between the MAPK Slt2 of the PKC1-MAPK pathway and Grx3/Grx4 glutaredoxins is required for the oxidative stress response in budding yeast

dc.contributor.authorPujol Carrión, Núria
dc.contributor.authorTorre Ruiz, M. A. de la
dc.date.accessioned2017-01-20T10:46:59Z
dc.date.embargoEndDate2025-01-01
dc.date.issued2017
dc.description.abstractThis study demonstrates that both monothiol glutaredoxins Grx3 and Grx4 physically interact with the MAPK Slt2 forming a complex involved in the cellular response to oxidative stress. The simultaneous absence of Grx3 and Grx4 provokes a serious impairment in cell viability, Slt2 activation and Rlm1 transcription in response to oxidative stress. Both in vivo and in vitro results clearly show that Slt2 can independently bind either Grx3 or Grx4 proteins. Our results suggest that Slt2 form iron/sulphur bridged clusters with Grx3 and Grx4. For the assembly of this complex, cysteines of the active site of each Grx3/4 glutaredoxins, glutathione and specific cysteine residues from Slt2 provide the ligands. One of the ligands of Slt2 is required for its dimerisation upon oxidative treatment and iron repletion. These interactions are relevant for the oxidative response, given that mutants in the cysteine ligands identified in the complex show a severe impairment of both cell viability and Slt2 phosphorylation upon oxidative stress. Grx4 is the relevant glutaredoxin that regulates Slt2 phosphorylation under oxidative conditions precluding cell survival. Our studies contribute to extend the functions of both monothiol glutaredoxins to the regulation of a MAPK in the context of the oxidative stress response.ca_ES
dc.description.sponsorshipWe thank Dr Angel Mozo Villarías for his help in modelling Slt2, Grx3 and Grx4. We are very grateful to Dr Maria Molina for providing us with the plasmid pHR3 containing Slt2K54F and to Dr Enrique Herrero for giving us the strain grx5. We also wish to thank Xavier Calomarde for technical support with electron microscopy studies and to Silvia Areste for helpful technical assistance. This work was supported by the Spanish Ministerio de Economia y Competitividad through Grant BFU2012-31407.ca_ES
dc.identifier.doihttps://doi.org/10.1016/j.freeradbiomed.2016.12.023
dc.identifier.idgrec025515
dc.identifier.issn0891-5849
dc.identifier.urihttp://hdl.handle.net/10459.1/59058
dc.language.isoengca_ES
dc.publisherElsevierca_ES
dc.relationMICINN/PN2008-2011/BFU2012-31407
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.1016/j.freeradbiomed.2016.12.023ca_ES
dc.relation.ispartofFree Radical Biology and Medicine, 2017, vol. 103, p. 107-120ca_ES
dc.rights(c) Elsevier Inc, 2016ca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccessca_ES
dc.subjectSignallingca_ES
dc.subjectGlutaredoxinsca_ES
dc.subjectMAPKca_ES
dc.subjectOxidative stressca_ES
dc.subjectPKC1 pathwayca_ES
dc.subjectBudding yeastca_ES
dc.subjectIronca_ES
dc.subjectCell survivalca_ES
dc.titlePhysical interaction between the MAPK Slt2 of the PKC1-MAPK pathway and Grx3/Grx4 glutaredoxins is required for the oxidative stress response in budding yeastca_ES
dc.typearticleca_ES
dc.type.versionpublishedVersionca_ES
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