H2O2 Activates the Nuclear Localization of Msn2 and Maf1 through Thioredoxins in Saccharomyces cerevisiae
H2O2 Activates the Nuclear Localization of Msn2 and Maf1 through Thioredoxins in Saccharomyces cerevisiae
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DOI：
10.1128/ec.00106-09
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发表时间：
2009-09-01
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影响因子：
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通讯作者：
Chedin, Stephane
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作者：
Boisnard, Stephanie;Lagniel, Gilles;Chedin, Stephane
细胞对过氧化氢(H_2O_2)的反应以抑制与生长相关的过程和增强细胞防御重要基因的表达为特征。在萌芽酵母中，这种反应需要一组转录效应器的激活。其中一些基因，如转录激活子YAP1，是氧化应激所特有的；另一些，如转录激活子MSN2/4和负调控因子Maf1，可被广泛的应激条件激活。这些一般效应器如何被激活以应对氧化应激仍然是一个悬而未决的问题。在本研究中，我们证明了两个细胞质硫氧还蛋白Trx1和Trx2对于触发MSN2/4和Maf1的核积累是必不可少的，特别是在H_2O_2处理下。与之前对酵母所描述的许多胁迫条件相反，过氧化氢诱导的MSN2和Maf1的核积累与PKA激酶活性的下调无关。然而，我们发现PP2A磷酸酶活性对于推动Maf1去磷酸化及其随后的核积累是必不可少的，以响应H_2O_2处理。有趣的是，在这种情况下，PP2A活性的缺乏对MSN2的亚细胞定位没有影响，这表明H_2O_2信号通路通过硫氧还蛋白系统共享一条共同的路线，然后分叉激活这些通路的最终整合子MSN_2和Maf1。
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.