热休克同源蛋白70羧基端作用蛋白的功能及其与神经退行性疾病的关系  

Functions of carboxyl-terminus of Hsc70 interacting protein and its role in neurodegenerative disease

作　　者：严伟倩[1] 王俊岭[1] 唐北沙[1,2,3] 

机构地区：[1]中南大学湘雅医院神经内科,长沙410008 [2]医学遗传学国家重点实验室 [3]神经退行性疾病研究中心

出　　处：《中华医学遗传学杂志》2012年第4期426-430,共5页Chinese Journal of Medical Genetics

基　　金：国家科技支撑计划（十一五计划）（2006BA105A07）;国家重点基础研究发展计划（973计划）（2006cb500700）

摘　　要：神经退行性疾病是一组病因不明的慢性进行性神经损害。蛋白质的错误折叠和聚集是这类疾病共同的病理特征。热休克同源蛋白70羧基端作用蛋白（carboxyl—terminus of Hsc70 interacting protein，CHIP）具有双重功能，一方面可作为热休克蛋白的辅助因子，通过氨基端的34肽重复序列结构域与Hsp90和Hsc／HspT0相互作用，调节热休克蛋白介导的蛋白质异常折叠，同时又可作为E3泛素连接酶，通过羧基端的U—box结构域参与泛素一蛋白酶体系统（ubiqutin-proteasome system，UPS）介导的蛋白质降解过程。CHIP在分子伴侣系统和UPS的交互作用中扮演重要角色，对维持细胞内蛋白质稳态具有重要的作用。本文从CHIP蛋白的分子结构特点、生理功能、在细胞代谢中的作用、与神经退行性疾病的关系等方面进行综述。Neurodegenerative diseases are The cause is unclear, most of them share a same a group of chronic progressive neuronal damage disorders. pathological hallmark with misfold proteins accumulating in neurons. Carboxyl-terminus of Hsc70 interacting protein （CHIP） is a dual functional molecule, which has a N terminal tetratrico peptide repeat （TPR） domain that interacts with Hsc/Hsp70 complex and Hsp90 enabling CHIP to modulate the aberrant protein folding; and a C terminal U-box ubiquitin ligase domain that binds to the 26S subunit of the proteasome involved in protein degradation via ubiqutin-proteasome system. CHIP protein mediates interactions between the chaperone system and the ubiquitin-proteasome system, and plays an important role in maintaining the protein homeostasis in ceils. This article reviews the molecular characteristics and physiological functions of CHIP, and its role in cellular metabolism and discusses the relationship between CHIP dysfunction and neurodegenerative diseases.

关 键 词：热休克同源蛋白70羧基端作用蛋白 分子伴侣 E3泛素连接酶 蛋白质质量控制系统 泛索化 

分 类 号：R741[医药卫生—神经病学与精神病学]