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首页> 外文期刊>Cellular Signalling >Class I HDAC inhibition stimulates cardiac protein SUMOylation through a post-translational mechanism
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Class I HDAC inhibition stimulates cardiac protein SUMOylation through a post-translational mechanism

机译：I类HDAC抑制通过翻译后机制刺激心脏蛋白SUMO酰化

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Lysine residues are subject to amultitude of reversible post-translationalmodifications, including acetylation and SUMOylation. In the heart, enhancement of lysine acetylation or SUMOylation using histone deacetylase (HDAC) inhibitors or SUMO-1 gene transfer, respectively, has been shown to be cardioprotective. Here, we addressed whether there is crosstalk between lysine acetylation and SUMOylation in the heart. Treatment of cardiomyocytes and cardiac fibroblasts with pharmacological inhibitors of HDAC catalytic activity robustly increased conjugation of SUMO-1, but not SUMO-2/3, to several high molecular weight proteins in both cell types. The use of a battery of selective HDAC inhibitors and short hairpin RNAs demonstrated that HDAC2, which is a class I HDAC, is the primary HDAC isoformthat controls cardiac protein SUMOylation. HDAC inhibitors stimulated protein SUMOylation in the absence of de novo gene transcription or protein synthesis, revealing a post-translational mechanism of HDAC inhibitor action. HDAC inhibition did not suppress the activity of de- SUMOylating enzymes, suggesting that increased protein SUMOylation in HDAC inhibitor-treated cells is due to stimulation of SUMO-1 conjugation rather than blockade of SUMO-1 cleavage. Consistent with this, multiple components of the SUMO conjugation machinerywere capable of being acetylated in vitro. These findings reveal a novel role for reversible lysine acetylation in the control of SUMOylation in the heart, and suggest that cardioprotective actions of HDAC inhibitors are in part due to stimulation of protein SUMO-1-ylation inmyocytes and fibroblasts.
机译：赖氨酸残基经受多种可逆的翻译后修饰，包括乙酰化和SUMO化。在心脏中，使用组蛋白脱乙酰基酶（HDAC）抑制剂或SUMO-1基因转移分别增强赖氨酸乙酰化或SUMOylation具有心脏保护作用。在这里，我们探讨了心脏中赖氨酸乙酰化和SUMOylation之间是否存在串扰。用HDAC催化活性的药理学抑制剂处理心肌细胞和心脏成纤维细胞，在两种细胞类型中均能强烈增强SUMO-1（而非SUMO-2 / 3）与几种高分子量蛋白的结合。使用一系列选择性HDAC抑制剂和短发夹RNA证明，HDAC2是I类HDAC，是控制心脏蛋白质SUMOylation的主要HDAC亚型。在没有从头基因转录或蛋白质合成的情况下，HDAC抑制剂刺激了蛋白质的SUMOylation，揭示了HDAC抑制剂作用的翻译后机制。 HDAC抑制不能抑制去SUMO化酶的活性，这表明在HDAC抑制剂处理的细胞中蛋白质SUMO化的增加是由于SUMO-1结合的刺激而不是SUMO-1裂解的阻断。与此相一致，SUMO偶联机器的多个组件都能够在体外被乙酰化。这些发现揭示了可逆赖氨酸乙酰化在控制心脏SUMOylation中的新作用，并表明HDAC抑制剂的心脏保护作用部分是由于刺激了肌细胞和成纤维细胞中的SUMO-1-ylation蛋白。

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