IL-6受体泛素化调控机制

IL-6参与免疫、组织再生和代谢等生命活动，是重要的炎症因子。对IL-6诱导的信号转导的分子机制研究是近年来生物医学研究的热点之一。我们在前期工作中，发现MARCH3依赖泛素酶活性介导IL-6Ra发生泛素化修饰并降解。MARCH3能够剂量依赖的抑制IL-6诱导的STAT3激活；March3的缺失将导致小鼠更为剧烈的肠炎反应。根据这些结果我们提出假说：MARCH3是IL-6受体的E3泛素连接酶。本项目将充分利用分子、细胞生物学、生物化学及动物疾病模型，研究MARCH3在IL-6受体复合物介导的信号转导中功能，揭示IL-6受体泛素化修饰的分子机理，为寻找相关疾病的药物靶标、发展新型免疫干预策略提供科学基础。

IL-6 is an important inflammatory factor, which is involved in immune, tissue regeneration and metabolism. The molecular mechanism of IL-6-induced signaling is a key question in the past years. In our preliminary studies, we found that March3 mediates the ubiquitination and degradation of IL-6Ra in a ligase activity-dependent manner. March3 inhibits IL-6-induced ativivation of STAT3 in a dose-dependent manner. Deficiency of March3 promotes DSS-induced colitis. Based on these results, we hypothesize that March3 is the E3 ubiquitin ligase of IL-6 receptor. In this projects, we will investigate molecular mechanisms responsible for IL-6 recetor ubiquitination by MARCH3. This project will provide candidate targets of related diseases and scientific evidence for developing new immune intervention strategies.