Glutaredoxins Grx3 and Grx4 regulate nuclear localisation of Aft1 and the oxidative stress response in Saccharomyces cerevisiae

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2006Author
Nogues, Antoni
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Pujol Carrión, Núria;
Bellí i Martínez, Gemma;
Herrero Perpiñán, Enrique;
Nogues, Antoni;
Torre Ruiz, M. A. de la;
.
(2006)
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Glutaredoxins Grx3 and Grx4 regulate nuclear localisation of Aft1 and the oxidative stress response in Saccharomyces cerevisiae.
Journal of cell science, 2006, vol. 119, núm. 21, p. 4554-4564.
https://doi.org/10.1242/jcs.03229.
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Grx3 and Grx4, two monothiol glutaredoxins of
Saccharomyces cerevisiae, regulate Aft1 nuclear
localisation. We provide evidence of a negative regulation
of Aft1 activity by Grx3 and Grx4. The Grx domain of both
proteins played an important role in Aft1 translocation to
the cytoplasm. This function was not, however, dependent
on the availability of iron. Here we demonstrate that Grx3,
Grx4 and Aft1 interact each other both in vivo and in vitro,
which suggests the existence of a functional protein
complex. Interestingly, each interaction occurred
independently on the third member of the complex. The
absence of both Grx3 and Grx4 induced a clear enrichment
of G1 cells in asynchronous cultures, a slow growth
phenotype, the accumulation of intracellular iron and a
constitutive activation of the genes regulated by Aft1.
The grx3grx4 double mutant was highly sensitive to
the oxidising agents hydrogen peroxide and
t-butylhydroperoxide but not to diamide. The phenotypes
of the double mutant grx3grx4 characterised in this study
were mainly mediated by the Aft1 function, suggesting that
grx3grx4 could be a suitable cellular model for studying
endogenous oxidative stress induced by deregulation of the
iron homeostasis. However, our results also suggest that
Grx3 and Grx4 might play additional roles in the oxidative
stress response through proteins other than Aft1.
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Journal of cell science, 2006, vol. 119, núm. 21, p. 4554-4564European research projects
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