选择性自噬受体TAX1BP1的研究进展及意义

Research Progress and Significance of Selective Autophagy Receptor TAX1BP1

自噬是真核细胞内主要的降解系统之一,在清除细胞内受损物质方面发挥着重要作用。近年来,自噬与疾病的关系成为研究的热门话题。自噬功能的异常往往影响着疾病的发生、发展及预后。细胞通过自噬途径选择性地清除某些细胞质成分的过程称为选择性自噬。选择性自噬的发生通常需要自噬受体的参与,不同的自噬受体发挥的具体功能也不尽相同。其中,Tax1结合蛋白1(Tax1-binding protein 1,TAX1BP1)作为选择性自噬接头蛋白的一员,主要由一个SKIP羧基同源性域(SKIP carboxyl homology,SKICH)、一个微管相关蛋白I轻链3结合结构域(LC3-interacting region,LIR)、三个卷曲螺旋和一个羧基末端泛素锌指结合(ubiquitin-binding zinc finger,UBZ)结构域构成。这些结构域介导了TAX1BP1与其他蛋白质的相互作用,并在一定程度上对TAX1BP1在细胞中的功能产生影响。TAX1BP1同时调节NF-κB、JNK等信号通路;它广泛地参与到线粒体自噬、异体自噬以及溶酶体自噬等自噬进程中去;TAX1BP1的异常表达与炎症反应、恶性肿瘤及循环系统疾病的发生密切相关。该文主要对TAX1BP1的结构功能、调节的信号通路、与自噬的关系,以及其生理意义进行系统的总结,为今后TAX1BP1的研究提供新思路。

Autophagy is one of the main degradation systems in eukaryotic cells and plays an important role in removing damaged substances in cells.In recent years,the relationship between autophagy and disease has become a hot topic.Abnormal autophagy often affects the occurrence,development and prognosis of diseases.The process of selectively clearing some cytoplasmic components through autophagy is called selective autophagy.The occurrence of selective autophagy usually requires the participation of autophagy receptors,and different autophagy receptors play different functions.Among them,TAX1BP1 (Tax1-binding protein 1),as a member of selective autophagy adaptor protein,is mainly composed of a SKICH (SKIP carboxyl homology domain),a microtubule associated protein I light chain 3 binding region,three coiled coils and a C-terminal ubiquitin binding domain.These domains mediate the interaction between TAX1BP1 and other proteins,and affect the function of TAX1BP1 in cells to a certain extent.TAX1BP1 simultaneously regulates NF-κB,JNK and other signal pathways.It is widely involved in autophagy processes such as mitophagy,xenophagy and lysophagy.The abnormal expression of TAX1BP1 is closely related to inflammation,malignant tumors and circulatory diseases.This paper will systematically summarize the structure and function,regulated signal pathway,relationship with autophagy and the physiological significance of TAX1BP1,so as to provide new ideas for the research of TAX1BP1 in the future.