RIP1泛素化修饰调控程序性坏死的研究进展  

Research progress on RIP1 ubiquitination in regulating necroptosis

作　　者：董灵军 吴明[1] DONG Lingjun;WU Ming(Department of Thoracic Surgery,The Second Affiliated Hospital Zhejiang University School of Medicine,Hangzhou 310009,China)

机构地区：[1]浙江大学医学院附属第二医院胸外科,杭州310009

出　　处：《生命的化学》2021年第9期1900-1907,共8页Chemistry of Life

基　　金：浙江省自然科学基金重点项目(LZ20H010001)。

摘　　要：在过去的二十年中,随着对程序性坏死(necroptosis)研究的不断深入,学者们发现多种死亡受体激活可引起程序性坏死,其中研究最为透彻的是肿瘤坏死因子受体1(TNFR1)。在TNFR1激活引起细胞发生程序性坏死的信号转导过程中,细胞内先后形成复合物Ⅰ(complexⅠ)和坏死小体(necrosome)。这2个复合物中都含有一个关键蛋白——受体相互作用蛋白激酶1(RIP1)。复合物Ⅰ中的RIP1存在多种多聚泛素化修饰,且多聚泛素化修饰种类和水平的变化能决定细胞的命运——炎症、凋亡或坏死。此外,坏死小体中的RIP1也存在多聚泛素化修饰。然而,RIP1的泛素化修饰如何调控细胞信号转导和促进坏死小体的形成尚未被完全阐明。该文对RIP1泛素化修饰调控细胞程序性坏死的研究进展进行综述。In the past two decades, with the deepening of research on necroptosis, scholars found that necroptosis could be caused by activation of several death receptors, of which tumor necrosis factor receptor 1(TNFR1) was the most studied. Activation of TNFR1 induces the formation of two transient complexes, named complex Ⅰ and necrosome, and both of them contain a key protein, receptor-interacting protein kinase 1(RIP1).RIP1 in complex Ⅰ is extensively modified by different types of ubiquitination, and changes in the type and level of ubiquitination can determine the fate of a cell, including inflammation, apoptosis or necroptosis. Besides,it has been found that ubiquitination also exists in necrosome. However, it is still unclear how the ubiquitination of RIP1 regulates signal transduction and promotes the formation of necrosome. Here, the research progress of RIP1 ubiquitination on the regulation of necroptosis is reviewed based on existing evidence.

关 键 词：程序性坏死 受体相互作用蛋白激酶1 泛素化修饰 去泛素化酶 肿瘤坏死因子受体1 

分 类 号：Q343[生物学—遗传学]