Department of Biochemistry and Molecular Biology, University of Massachusetts, 240 Thatcher Road, Amherst, MA, 01003, USA.
Program in Molecular and Cellular Biology, University of Massachusetts, Amherst, MA, 01003, USA.
Protein J. 2019 Jun;38(3):317-329. doi: 10.1007/s10930-019-09831-w.
The site of protein folding and maturation for the majority of proteins that are secreted, localized to the plasma membrane or targeted to endomembrane compartments is the endoplasmic reticulum (ER). It is essential that proteins targeted to the ER are properly folded in order to carry out their function, as well as maintain protein homeostasis, as accumulation of misfolded proteins could lead to the formation of cytotoxic aggregates. Because protein folding is an error-prone process, the ER contains protein quality control networks that act to optimize proper folding and trafficking of client proteins. If a protein is unable to reach its native state, it is targeted for ER retention and subsequent degradation. The protein quality control networks of the ER that oversee this evaluation or interrogation process that decides the fate of maturing nascent chains is comprised of three general types of families: the classical chaperones, the carbohydrate-dependent system, and the thiol-dependent system. The cooperative action of these families promotes protein quality control and protein homeostasis in the ER. This review will describe the families of the ER protein quality control network and discuss the functions of individual members.
大多数分泌型、定位于质膜或靶向内质网隔室的蛋白质的折叠和成熟位点是内质网（ER）。靶向内质网的蛋白质必须正确折叠才能发挥其功能，并维持蛋白质的内稳态，因为错误折叠的蛋白质积累可能导致细胞毒性聚集物的形成。由于蛋白质折叠是一个易错的过程，内质网包含蛋白质质量控制网络，这些网络的作用是优化客户蛋白质的正确折叠和运输。如果蛋白质无法达到其天然状态，它将被靶向内质网滞留并随后降解。内质网的蛋白质质量控制网络监督决定成熟新生链命运的评估或询问过程，该网络由三种一般类型的家族组成：经典伴侣蛋白、碳水化合物依赖系统和硫醇依赖系统。这些家族的协同作用促进了内质网中的蛋白质质量控制和蛋白质内稳态。这篇综述将描述内质网蛋白质质量控制网络的家族，并讨论各个成员的功能。
