Parkin的结构与功能及其相关致病机制的研究进展

Research progress on the structure and function of Parkin and its related mechanism in diseases

Parkin(E3 Ubiquitin Ligase)具有E3泛素连接酶活性,其活性的减弱或丧失不仅会导致帕金森氏症,同时与多种癌症密切相关。该文首先对Parkin(E3 Ubiquitin Ligase)的结构以及活化的过程进行详细阐述,表明Parkin在生理状态下为自抑制构象,需要在PINK1的辅助下进行活化。通过综述Parkin相关致病机制,发现其蛋白功能的异常在帕金森氏症(Parkinson′s Disease,PD)中引起神经细胞的凋亡,而在肿瘤中引起细胞增殖失控,同一基因突变导致两种截然相反的细胞命运引发思考。因此,探究Parkin在两种疾病中的致病机理意义重大,一种疾病的治疗方法可为另一种疾病的靶向治疗开辟新途径。

Parkin,an E3 ubiquitin ligase.The weakening or loss of its activity will not only lead to Parkinson′s disease,but is also closely related to a variety of cancers.This article elaborates on the structure and activation process of Parkin,showing that Parkin is a self-inhibitory conformation under physiological conditions and needs to be activated with the assistance of PINK1.By reviewing the related pathogenic mechanisms of Parkin,it is hard to imagine that a single gene mutation can exert entirely opposite effects i.e.,neurons apoptosis in Parkinson′s Disease(PD)and cell proliferation in cancers.Therefore,it is of great significance to explore the pathogenic mechanism of Parkin in two diseases.The treatment of one disease can open up a new way for the targeted therapy of another disease.