蛋白质甲基化修饰是一类十分重要的蛋白质翻译后修饰，这一过程在多种生命活动中发挥至关重要的作用，特定的蛋白质甲基化修饰异常往往会导致多种疾病和癌症产生。MLL家族蛋白作为一类组蛋白H3K4甲基转移酶而被人们熟知，但近年来越来越多的研究表明其存在一些非组蛋白底物。此外，虽然MLL家族蛋白被报道可以调控p53的功能，但具体分子机制尚不明确，p53是否可以作为MLL的甲基化底物也未得以阐明。本项目将致力于探究MLL家族蛋白和p53蛋白的新关联和新功能。将联合运用结构生物学、分子生物学、生物化学、细胞生物学等多种手段开展以下几方面的研究（1）MLL家族蛋白是否可以介导p53的甲基化,（2）MLL催化p53甲基化的分子机制,（3）MLL介导的p53甲基化的体内功能。上述研究成果将为人们理解MLL和p53的体内功能和病理作用提供重要的理论依据，并为一系列遗传疾病或癌症的治疗提供潜在的新靶点。

Protein methylation is a critical protein post-translational modification which plays important roles in multiple cellular processes. Abnormal protein methylation has been linked to many human diseases and cancers. MLL family proteins are well known as H3K4 methyltransferases while a growing number of non-histone substrates has been found to be methylated by MLL-family proteins. In addition, although MLL family proteins have been reported to regulate p53 function, the molecular mechanism remains unclear and whether p53 can be methylated by MLL family proteins remains elusive. In this project, we will focus on exploring new correlations and functions between MLL family proteins and p53. We will employ a combination of structural biology, molecular biology, biochemistry, cell biology techniques to study whether p53 can be methylated by MLL family proteins, and reveal the molecular mechanisms and functions of MLL-mediated p53 methylation. The proposed study will provide a solid foundation for our understanding of the structure and function of these proteins, and also provide clues for drug design and novel therapeutic approaches for some human diseases.