Thiol peroxidases mediate specific genome-wide regulation of gene expression in response to hydrogen peroxide
Thiol peroxidases mediate specific genome-wide regulation of gene expression in response to hydrogen peroxide
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DOI：
10.1073/pnas.1010721108
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发表时间：
2011-02-15
影响因子：
11.1
通讯作者：
Gladyshev, Vadim N.
中科院分区：
文献类型：
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作者：
Fomenko, Dmitri E.;Koc, Ahmet;Gladyshev, Vadim N.
过氧化氢被认为通过直接氧化许多细胞蛋白质来调节细胞过程，而抗氧化剂，最显著的是硫醇过氧化物酶，被认为可以减少过氧化物并抑制H2O2反应。然而，巯基过氧化物酶也参与了转录因子和信号传导的激活。目前尚不清楚这些酶是否刺激或抑制氧化还原调节，以及这种调节是否广泛或仅限于少数细胞组分。在此，我们发现，酿酒酵母细胞缺乏所有八个巯基过氧化物酶是可行的，并承受氧化还原应力。它们在转录上对各种氧化还原处理作出反应，但不能激活和抑制H2O2引起的基因表达。涉及氧化还原转录因子的进一步研究表明，巯基过氧化物酶是响应H2O2的全球基因表达的主要调节因子。这些数据表明，巯基过氧化物酶的感觉和转移氧化信号的信号传导蛋白和调节转录，而H2O2和其他细胞蛋白质之间的直接相互作用起着次要的作用。
Hydrogen peroxide is thought to regulate cellular processes by direct oxidation of numerous cellular proteins, whereas antioxidants, most notably thiol peroxidases, are thought to reduce peroxides and inhibit H2O2 response. However, thiol peroxidases have also been implicated in activation of transcription factors and signaling. It remains unclear if these enzymes stimulate or inhibit redox regulation and whether this regulation is widespread or limited to a few cellular components. Herein, we found that Saccharomyces cerevisiae cells lacking all eight thiol peroxidases were viable and withstood redox stresses. They transcriptionally responded to various redox treatments, but were unable to activate and repress gene expression in response to H2O2. Further studies involving redox transcription factors suggested that thiol peroxidases are major regulators of global gene expression in response to H2O2. The data suggest that thiol peroxidases sense and transfer oxidative signals to the signaling proteins and regulate transcription, whereas a direct interaction between H2O2 and other cellular proteins plays a secondary role.