Protein degradation in human disease.-猫眼课题宝

人类疾病中的蛋白质降解。

DOI：

10.1007/978-3-642-56373-7_5

发表时间：

2002

期刊：

Progress in molecular and subcellular biology

影响因子：

通讯作者：

中科院分区：

文献类型：

作者：

Richard K. Plemper;A. Hammond

蛋白质的细胞内降解构成了各种中央细胞过程中的重要调节开关。此外，它提供了氨基酸再生的蛋白质周转的基本机制。蛋白质降解的几种机制是已知的，但大多数调节蛋白通过泛素-蛋白酶体途径降解。因此，该途径涉及细胞凋亡、细胞周期进程、免疫应答、发育、转录调节、信号转导和受体下调的控制。这种和其他蛋白水解机制的复杂性质，以及它们在细胞过程中的关键作用，构成了与几种致病性疾病（获得性和遗传性）相关的许多畸变存在的基础。在本章中，蛋白质降解的两个主要机制，泛素蛋白酶体系统和溶酶体，将讨论与疾病有关的突变引起的特定步骤的途径，并从蛋白质突变，诱导其稳定或降解（总结在表1）。

Intracellular degradation of proteins constitutes a vital regulatory switch in a variety of central cellular processes. Additionally, it provides an essential mechanism in protein turnover for amino acid regeneration. Several mechanisms of protein degradation are known, but the majority of regulatory proteins are degraded through the ubiquitin-proteasome pathway. This pathway has thus been implicated in the control of apoptosis, cell cycle progression, immune response, development, transcriptional regulation, signal transduction, and receptor down-regulation. The complex nature of this, and other proteolysis mechanisms, and their critical roles in cellular processes underlies the existence of many aberrations related to several pathogenic diseases, both acquired and inherited. In this chapter, two major mechanisms of protein degradation, the ubiquitin proteasome system and the lysosome, will be discussed in relation to diseases resulting from mutations in a particular step of the pathways, and from mutations in proteins that induce their stabilization or degradation (summarized in Table 1).