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Título:
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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
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Autor/a:
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Pujol Carrión, Núria; Torre Ruiz, M. A. de la
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Notas:
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This 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.
We 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. |
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Materia(s):
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-Signalling
-Glutaredoxins
-MAPK
-Oxidative stress
-PKC1 pathway
-Budding yeast
-Iron
-Cell survival |
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Derechos:
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(c) Elsevier Inc, 2016
info:eu-repo/semantics/restrictedAccess |
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Tipo de documento:
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article
publishedVersion |
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Editor:
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Elsevier
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Compartir:
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