题目： Molecular mechanisms of tumor necrosis factor-induced necrosis (necroptosis)

报告人：Prof. Jiahuai Han

时间 : 12月3日(周三) 14:00-16:00pm

地点 : 金光生命科学大楼101报告厅

邀请人：蒋争凡教授，北京大学生命科学学院, 生命科学联合中心

电话：62757923

Abstract：

Tumor necrosis factor-a (TNF) is a proinflammatory cytokine that play an essential role in systematic inflammation. However, under certain conditions, the TNF signaling can be re-directed to cell death. TNF can induce either apoptotic or necrotic cell death depending on cell type and cellular conditions. TNF-induced cell death serves as a prototypic model system to study the molecular mechanisms of both apoptosis and necrosis. Necroptosis is a type of programmed necrosis which is mediated by RIP1 and RIP3. TNF-induced necrosis is necroptosis. Whether the cells undergo apoptosis or necroptosis depends on the level of receptor interacting protein (RIP) 3 in the given cell. High level of RIP3 can convert the type of cell death from apoptosis to necroptosis, which involves RIP1-RIP3 heterodimerization, RIP3-RIP3 homodimerization, amyloid complex formation and phosphorylation of caspase-8 by RSK. RIP3 auto-phosphorylation is essential for the recruitment of MLKL, a major downstream target of RIP3 whose translocation to plasma membrane is essential for the execution of necroptosis. The phosphorylation of RIP3 is a reversible process and we have recently identified Ppm1b is a RIP3 phosphatase and a negative regulator of RIP3 dependent necroptosis in vitro and in vivo. This presentation will summarize current knowledge of the mechanisms of necroptosis and provide our new data in understanding the mechanism of necroptosis.