SETD2是哺乳动物体内组蛋白H3K36的三甲基化酶，从酵母到哺乳动物都高度保守。SETD2参与调控mRNA的成熟和可变剪切，其突变与肿瘤发生相关。本实验室通过酵母双杂交实验，找到与SETD2相互作用的泛素E3连接酶SAP1以及其它多个蛋白，并初步证明SAP1调控SETD2的多聚泛素化和蛋白稳定性。本项目计划在此基础上，利用生化实验，高通量测序技术和小鼠模型等方法，在体内和体外证明SETD2及其相互作用蛋白，对组蛋白修饰、RNA可变剪切、基因转录和肿瘤发生的作用及其分子机制，为恶性肿瘤的诊断治疗提供新的理论基础和分子靶标。

In mammals, SETD2 is the major trimethyltransferase for histone H3 at lysine 36. It is highly conserved from yeast to human. SETD2 involves in the regulation of mRNA maturation and alternative splicing. Its mutations are also frequently associated with cancer. By using yeast two-hybrid screen, we identified multiple SETD2 associated proteins including a ubiquitin E3 ligase, SAP1. The initial data proved SAP1 regulates SETD2 ubiquitination and protein stability. We are planning to study the roles of SETD2 and its associated protein in regulating histone modification, RNA alternative splicing, transcription and tumorigenesis, by combining biochemistry techniques, high throughput sequencing and animal model. Our study will provide new theoretical foundation and new drug targets for the diagnosis and treatment of malignant tumors.