SUMOylation is a reversible posttranslational modification pathway catalyzing the conjugation of small ubiquitin-related modifier (SUMO) proteins to lysine residues of distinct target proteins. SUMOylation modifies a wide variety of cellular regulators thereby affecting a multitude of key processes in a highly dynamic manner. The SUMOylation pathway displays a hallmark in cellular stress-adaption, such as heat or redox stress. It has been proposed that enhanced cellular SUMOylation protects the brain during ischemia, however, little is known about the specific regulation of the SUMO system and the potential target proteins during cardiac ischemia and reperfusion injury (I/R). By applying left anterior descending (LAD) coronary artery ligation and reperfusion in mice, we detect dynamic changes in the overall cellular SUMOylation pattern correlating with decreased SUMO deconjugase activity during I/R injury. Further, unbiased system-wide quantitative SUMO-proteomics identified a sub-group of SUMO targets exhibiting significant alterations in response to cardiac I/R. Notably, transcription factors that control hypoxia- and angiogenesis-related gene expression programs, exhibit altered SUMOylation during ischemic stress adaptation. Moreover, several components of the ubiquitin proteasome system undergo dynamic changes in SUMO conjugation during cardiac I/R suggesting an involvement of SUMO signaling in protein quality control and proteostasis in the ischemic heart. Altogether, our study reveals regulated candidate SUMO target proteins in the mouse heart, which might be important in coping with hypoxic/proteotoxic stress during cardiac I/R injury.

中文翻译：

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分析小鼠 SUMO 蛋白质组对心脏缺血和再灌注损伤的反应


SUMO化是一种可逆的翻译后修饰途径，催化小泛素相关修饰剂 (SUMO) 蛋白与不同靶蛋白的赖氨酸残基的缀合。 SUMO化修饰多种细胞调节因子，从而以高度动态的方式影响多个关键过程。 SUMOylation 途径显示了细胞应激适应的标志，例如热或氧化还原应激。有人提出，增强的细胞 SUMO 化可以在缺血期间保护大脑，然而，人们对 SUMO 系统的具体调节以及心脏缺血和再灌注损伤 (I/R) 期间潜在的靶蛋白知之甚少。通过对小鼠进行左前降支 (LAD) 冠状动脉结扎和再灌注，我们检测到与 I/R 损伤期间 SUMO 解偶联酶活性降低相关的整体细胞 SUMO 化模式的动态变化。此外，无偏倚的全系统定量 SUMO 蛋白质组学确定了 SUMO 靶标的一个亚组，这些靶标在对心脏 I/R 的反应中表现出显着的变化。值得注意的是，控制缺氧和血管生成相关基因表达程序的转录因子在缺血应激适应过程中表现出改变的 SUMOylation。此外，在心脏缺血再灌注期间，泛素蛋白酶体系统的几个组件在 SUMO 结合中经历动态变化，表明 SUMO 信号传导参与缺血心脏的蛋白质质量控​​制和蛋白质稳态。总而言之，我们的研究揭示了小鼠心脏中受调节的候选 SUMO 靶蛋白，这对于应对心脏 I/R 损伤期间的缺氧/蛋白毒性应激可能很重要。