自噬与泛素化蛋白降解途径的分子机制及其功能简介.PDF

HEREDITAS (Beijing) 2012 1 , 34(1): 5―18 ISSN 0253-9772 综 述 DOI: 10.3724/SP.J.1005.2012.00005 自噬与泛素化蛋白降解途径的分子机制及其功能 陈科, 程汉华, 周荣家 , 430072 细胞内所有的蛋白质和大多数的细胞外蛋白都在不断的进行更新, 即它们在不断地被降解, 并被新合成 的蛋白质取代。细胞内蛋白的降解主要通过两个途径, 即自噬和泛素蛋白酶体系统。自噬是一种由溶酶体介导 的细胞内过多或异常蛋白质的降解机制。在细胞内主要有3 种类型的自噬, 即分子伴侣介导的自噬、微自噬和 巨自噬。泛素蛋白酶体系统是由泛素介导的一种高度复杂的蛋白降解机制, 它参与降解细胞内许多蛋白质并且 这个过程具有高度特异性。细胞内蛋白质的降解参与调节许多细胞过程, 包括细胞周期、DNA 修复、细胞生长 和分化、细胞质量的控制、病原生物的感染反应和细胞凋亡等。许多严重的人类疾病被认为是由于蛋白质降解 系统的紊乱而引起的。文章综述了自噬和泛素化途径及其分子机制, 以及蛋白质降解系统紊乱的病理学意义。 蛋白质降解; 自噬; 泛素蛋白酶体系统 Molecular mechanisms and functions of autophagy and the ubiq- uitin-proteasome pathway CHEN Ke, CHENG Han-Hua, ZHOU Rong-Jia Life Science College , Wuhan University, Wuhan 430072, China Abstract: All proteins in eukaryotic cells are continually being degraded and replaced. Autophagy and the ubiq- uitin-proteasome system are two mechanisms for intracellular protein degradation. Autophagy is mediated by lysosome, and is further divided into chaperone-mediated autophagy, microautophagy and macroautophagy. The ubiquitin-proteasome system is highly complex and mediated by ubiquitin, which participates in intracellular protein degradation in a specific manner. It is now known that degradation of intracellular proteins is involved in regulation of a series of cellular processes, including cell-cycle division, DNA repair, cell growth and differentiation, quality control, pathogen infection, and apoptosis. The aberrations in the protein degradation systems are involved in many serious human diseases. The present review sum- marizes the mechanisms of protein degradation and related human diseases. Keywords: prot