蛋白质甲基化在NF-κB信号途径中的作用及其分子调控机制

NF-κB信号通路是免疫和炎症反应中最关键的信号通路之一。蛋白质翻译后修饰在该信号通路的激活中起着关键作用，包括磷酸化、乙酰化和泛素化等等。近年来我们实验室和国际上其它研究小组发现MLL1等蛋白质甲基化酶在NF-κB信号通路中也起着重要的调节作用。本项目计划在前期工作的基础上，利用本实验室构建的人类蛋白质甲基化酶的表达克隆文库和siRNA文库，筛选调节NF-κB信号通路激活的重要甲基化酶，并研究其分子机制。我们已经完成首次筛选。初步研究结果显示甲基化酶PMT5与TRADD相互作用，并调节TRAF2的功能。本项目将较系统地研究和揭示蛋白质甲基化在NF-κB信号通路中的作用，为炎症相关疾病的诊断和治疗提供新的理论基础，为药物研制提供新靶标。

NF-κB signaling pathway is one of the most important pathways in inflammation response and immunity. The post translational modifications of proteins play key roles in the activation of NF-κB pathway, including phosphorylation, acetylation and ubiquitination. Recently, we and other groups found that protein methyltransferases, such as MLL1, has important functions in regulating the pathway. Based on the previous results, our project is going to screen for novel methyltransferases regulating NF-κB activation, by using the expression clone library and siRNA library of human protein methyltransferases. We have finished the first round of screen and got several candidate genes. Our preliminary data showed that PMT5, one of the candidates, is associated with TRADD and regulates the function of TRAF2. Our project will study and reveal the roles of protein methyltransferases in NF-κB signaling pathways systematically. It will provide new theoretical bases for the diagnosis and treatment of inflammation related diseases, as well as new targets for drug design.