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Eukaryotic Cell, September 2009, p. 1429-1438, Vol. 8, No. 9
1535-9778/09/$08.00+0     doi:10.1128/EC.00106-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

H2O2 Activates the Nuclear Localization of Msn2 and Maf1 through Thioredoxins in Saccharomyces cerevisiae{triangledown}

Stéphanie Boisnard,1 Gilles Lagniel,1 Cecilia Garmendia-Torres,2 Mikael Molin,1 Emmanuelle Boy-Marcotte,2 Michel Jacquet,2 Michel B. Toledano,3 Jean Labarre,1 and Stéphane Chédin1*

CEA, IBITECS, SBIGEM, LBI, F-91191 Gif-sur-Yvette Cedex, France,1 CNRS, Université Paris-Sud, UMR 8621, F-91405 Orsay Cedex, France,2 CEA, IBITECS, SBIGEM, LSOC, F-91191 Gif-sur-Yvette Cedex, France3

Received 10 April 2009/ Accepted 26 June 2009

The cellular response to hydrogen peroxide (H2O2) is characterized by a repression of growth-related processes and an enhanced expression of genes important for cell defense. In budding yeast, this response requires the activation of a set of transcriptional effectors. Some of them, such as the transcriptional activator Yap1, are specific to oxidative stress, and others, such as the transcriptional activators Msn2/4 and the negative regulator Maf1, are activated by a wide spectrum of stress conditions. How these general effectors are activated in response to oxidative stress remains an open question. In this study, we demonstrate that the two cytoplasmic thioredoxins, Trx1 and Trx2, are essential to trigger the nuclear accumulation of Msn2/4 and Maf1, specifically under H2O2 treatment. Contrary to the case with many stress conditions previously described for yeast, the H2O2-induced nuclear accumulation of Msn2 and Maf1 does not correlate with the downregulation of PKA kinase activity. Nevertheless, we show that PP2A phosphatase activity is essential for driving Maf1 dephosphorylation and its subsequent nuclear accumulation in response to H2O2 treatment. Interestingly, under this condition, the lack of PP2A activity has no impact on the subcellular localization of Msn2, demonstrating that the H2O2 signaling pathways share a common route through the thioredoxin system and then diverge to activate Msn2 and Maf1, the final integrators of these pathways.

* Corresponding author. Mailing address: CEA, IBITECS, SBIGEM, LBI, Bâtiment 142, F-91191 Gif-sur-Yvette Cedex, France. Phone: (33) 1 6908 9718. Fax: (33) 1 6908 8046. E-mail: stephane.chedin{at}cea.fr

{triangledown} Published ahead of print on 6 July 2009.

Eukaryotic Cell, September 2009, p. 1429-1438, Vol. 8, No. 9
1535-9778/09/$08.00+0     doi:10.1128/EC.00106-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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