蛋白质丙二酰化修饰是2011年发现的新型蛋白质翻译后修饰。申请人首次发现蛋白质丙二酰化修饰与2型糖尿病相关，并发现丙二酰辅酶A通过修饰果糖二磷酸醛缩酶B的关键位点（107位赖氨酸残基）而抑制糖酵解（Mol Cell Proteomics，2015），提示这一新型蛋白质翻译后修饰具有潜在生理病理作用。后续研究表明肝癌组织中蛋白质丙二酰化修饰水平降低、糖酵解速率升高。拟聚焦蛋白质丙二酰化修饰与肿瘤细胞糖酵解（Warburg效应）之间的潜在关联，开展以下研究：1. 构建并扩展蛋白质丙二酰化修饰组；2. 分析发生丙二酰化修饰的蛋白质及其相互作用网络；3. 确定蛋白质丙二酰化修饰影响肿瘤细胞糖酵解的作用机制；4. 解析肿瘤细胞调控蛋白质丙二酰化修饰水平以维持高速糖酵解的分子机理。研究结果有助于深入理解蛋白质丙二酰化修饰调控细胞能量代谢、参与重要生命活动过程及重大疾病发生发展的分子机理。

Protein lysine malonylation is a new protein posttranslational modification (PTM) identified in 2011. However, its potential roles associated with human diseases remain largely unknown. The applicant detected an elevated lysine malonylation in liver of type 2 diabetes mice models, and revealed that malonylation of fructose bisphosphate aldolase B at K107 site decreased its enzymatic activity and downregulated glycolysis (Mol Cell Proteomics, 2015). Further study indicated that protein malonylation levels in hepatoma tissues were lower, and the glycolytic capacities were higher, suggesting the relationship between the protein malonylation and enhanced glycolysis in cancer cells (The Warburg effect). The present application will be focused on: 1, The construction and expandation of protein malonylome. 2, The core malonylated protein(s) and their interaction networks. 3, The molecular mechanism underlying the regulation of glycolysis by protein malonylation. 3, The mechanism by which cancer cells maintain high glycolytic capacity via dynamic regulation of protein malonylation. The results of present investigation will be helpful for the understanding of the involvement of protein malonylation in the pathophysiology of diseases.