RIPK3翻译后修饰调控细胞程序性坏死的研究进展

The Regulation of Necroptosis by Post-Translational Modifications of RIPK3

细胞程序性坏死是一种不依赖于Caspase、可调控的细胞死亡方式,参与多种疾病的病理过程,如病毒或病原菌感染、动脉硬化、心脏缺血再灌注和肿瘤等。受体相互作用蛋白激酶3(receptor-interacting protein kinase 3,RIPK3)是细胞程序性坏死的关键调控分子,可与受体相互作用蛋白激酶1(receptor-interacting protein kinase 1,RIPK1)形成坏死小体,激活混合谱系激酶结构域样蛋白(mixed lineage kinase domain-like pseudokinase,MLKL),导致细胞膜破裂和细胞死亡。近年来,越来越多研究发现RIPK3活性可受多种翻译后修饰如磷酸化、泛素化、糖基化和蛋白水解切割等调控。该文就RIPK3翻译后修饰在调控细胞程序性坏死信号转导中的作用进行综述,期望为靶向RIPK3的药物设计及细胞程序性坏死相关疾病的治疗提供理论依据。

Necroptosis is a caspase-independent programmed cell death which has been widely implicated in many pathologies,such as viral or pathogen infection,atherosclerosis,cardiac ischemia-reperfusion and cancer.RIPK3(receptor-interacting protein kinase 3)has emerged as a critical regulator of necroptosis,which can interact with RIPK1(receptor-interacting protein kinase 1)to form a protein complex called necrosome and then active MLKL(mixed lineage kinase domain-like pseudokinase)to cause plasma membrane rupture and cell death.In recent years,increasing studies have found that the activity of RIPK3 is regulated by multiple post-translational modifications,including phosphorylation,ubiquitylation,GlcNAcylation and proteolytic cleavage.This article reviews the role of post-translational modifications of RIPK3 in necroptosis,which may provide theoretical basis for drug design targeting RIPK3 and treatment of necroptosis-related diseases.