Temasek Life Sciences Laboratory, National University of Singapore, Singapore 117604.
Cold Spring Harb Perspect Biol. 2012 Dec 1;4(12):a013193. doi: 10.1101/cshperspect.a013193.
Protein misfolding is a common cellular event that can produce intrinsically harmful products. To reduce the risk, quality control mechanisms are deployed to detect and eliminate misfolded, aggregated, and unassembled proteins. In the secretory pathway, it is mainly the endoplasmic reticulum-associated degradation (ERAD) pathways that perform this role. Here, specialized factors are organized to monitor and process the folded states of nascent polypeptides. Despite the complex structures, topologies, and posttranslational modifications of client molecules, the ER mechanisms are the best understood among all protein quality-control systems. This is the result of convergent and sometimes serendipitous discoveries by researchers from diverse fields. Although major advances in ER quality control and ERAD came from all model organisms, this review will focus on the discoveries culminating from the simple budding yeast.
蛋白质错误折叠是一种常见的细胞事件，可能产生内在有害产物。为了降低风险，质量控制机制被部署来检测和消除错误折叠、聚集和未组装的蛋白质。在分泌途径中，主要是内质网相关降解（ERAD）途径发挥这一作用。在这里，专门的因子被组织起来监测和处理新生多肽的折叠状态。尽管客户分子的结构、拓扑结构和翻译后修饰很复杂，但 ER 机制是所有蛋白质质量控制系统中最被理解的。这是来自不同领域的研究人员的趋同甚至有时是偶然发现的结果。尽管 ER 质量控制和 ERAD 的重大进展来自所有模式生物，但本综述将重点介绍从简单的出芽酵母中得出的发现。
