MG53蛋白的翻译后修饰调节及其应用研究

MG53在多种重要的生理学功能中发挥作用，是多种疾病的关键致病因子。作为组织保护因子，无论在内源或外源过表达MG53对于心脏、骨骼肌、肺脏、肾脏、大脑和皮肤等组织都有显著保护作用；同时MG53泛素E3连接酶活性在胰岛素抵抗中发挥关键作用；申请者作为通讯作者的最新Circulation文章揭示：MG53作为肌肉因子，分泌到循环中调节机体许多重要器官的胰岛素敏感性，而提高血液MG53水平就会抑制多种组织的胰岛素敏感性。为此，寻找没有胰岛素抵抗副作用而保留细胞保护好功能的MG53蛋白衍生物，是MG53临床应用的重要方向。本研究通过研究MG53翻译后修饰，深入了解MG53的调节机制，加深对MG53这一治疗靶标的了解，更重要的是找到MG53突变体，来实现本研究的设想，为下一步临床转化奠定基础。

Mitsugumin 53 (MG53) is a multi-functional TRIM-family protein, which has been shown that MG53 not only plays important physiological roles but also acts as a crucial pathogenic factor of various disease. MG53 preserves multiple organs during ischemia-reperfusion injury, including heart, skeletal muscle, lung, kidney, skin and brain. But importantly, MG53 is identified as a novel myokine which mediates the insulin-resistance of multiple-organs in our paper recently published in Circulation. Here we try to find the post-translational modification of MG53, and one functional phosphorylation site (Serine 255) is identified. The MG53 mutation of this site shows low insulin-resistance effect and maintain protection effects. This study will let us deeply understand MG53 and find a new angle to MG53 translational application.