Master redox regulator Trx1 upregulates SMYD1 & modulates lysine methylation.
Master redox regulator Trx1 upregulates SMYD1 & modulates lysine methylation.
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DOI：
10.1016/j.bbapap.2015.09.006
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发表时间：
2015-12
期刊：
影响因子：
--
通讯作者：
Li H
中科院分区：
文献类型：
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作者：
Liu T;Wu C;Jain MR;Nagarajan N;Yan L;Dai H;Cui C;Baykal A;Pan S;Ago T;Sadoshima J;Li H
硫氧还蛋白1（Trx1）是一种抗氧化蛋白，其调节蛋白质二硫键还原、转亚硝基化、去亚硝基化和其他氧化还原翻译后修饰。为了更好地了解Trx 1如何调节心肌缺血后的下游保护性细胞信号传导事件，我们对心脏特异性过表达Trx 1的转基因小鼠胸主动脉缩窄应激处理后的左心室（LV）进行了表达蛋白质组学研究，该动物模型已被证明比非转基因小鼠承受更多的压力。虽然以前的氧化还原翻译后修饰蛋白质组学研究发现，一些细胞蛋白质网络的调控Trx1介导的二硫键还原和转亚硝基化，我们发现，Trx1调节的蛋白质的表达数量有限。在这项研究中发现上调的蛋白质包括SET和MYND结构域蛋白1（SMYD1），这是一种在心脏和其他肌肉组织中高度表达的赖氨酸甲基转移酶，是心脏发育的重要调节因子。胸主动脉缩窄应激后Trx 1诱导SMYD 1的观察结果与逆行胎儿基因心脏保护假说一致。这里呈现的结果首次表明，除了作为蛋白质二硫键和亚硝化的主要氧化还原调节剂之外，Trx 1还可能通过调节SMYD 1表达来调节赖氨酸甲基化（一种非氧化还原翻译后修饰）。氧化还原信号和非氧化还原PTM调节之间的这种串扰可以提供新的见解Trx1的功能，独立于其作为蛋白质还原酶的直接功能。
Thioredoxin 1 (Trx1) is a antioxidant protein that regulates protein disulfide bond reduction, transnitrosylation, denitrosylation and other redox post-translational modifications. In order to better understand how Trx1 modulates downstream protective cellular signaling events following cardiac ischemia, we conducted an expression proteomics study of left ventricles (LVs) after thoracic aortic constriction stress treatment of transgenic mice with cardiac-specific over-expression of Trx1, an animal model that has been proven to withstand more stress than its non-transgenic littermates. Although previous redox post-translational modifications proteomics studies found that several cellular protein networks are regulated by Trx1-mediated disulfide reduction and transnitrosylation, we found that Trx1 regulates the expression of a limited number of proteins. Among the proteins found to be upregulated in this study was SET and MYND domain-containing protein 1 (SMYD1), a lysine methyltransferase highly expressed in cardiac and other muscle tissues and an important regulator of cardiac development. The observation of SMYD1 induction by Trx1 following thoracic aortic constriction stress is consistent with the retrograde fetal gene cardiac protection hypothesis. The results presented here suggest for the first time that, in addition to being a master redox regulator of protein disulfide bonds and nitrosation, Trx1 may also modulate lysine methylation, a non-redox post-translational modification, via the regulation of SMYD1 expression. Such crosstalk between redox signaling and a non-redox PTM regulation may provide novel insights into the functions of Trx1 that are independent from its immediate function as a protein reductase.