Department of Developmental and Molecular Biology, Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Cold Spring Harb Perspect Biol. 2010 Dec;2(12):a006734. doi: 10.1101/cshperspect.a006734. Epub 2010 Nov 10.
Cells maintain a healthy proteome through continuous evaluation of the quality of each of their proteins. Quality control requires the coordinated action of chaperones and proteolytic systems. Chaperones identify abnormal or unstable conformations in proteins and often assist them to regain stability. However, if repair is not possible, the aberrant protein is eliminated from the cellular cytosol to prevent undesired interactions with other proteins or its organization into toxic multimeric complexes. Autophagy and the ubiquitin/proteasome system mediate the complete degradation of abnormal protein products. In this article, we describe each of these proteolytic systems and their contribution to cellular quality control. We also comment on the cellular consequences resulting from the dysfunction of these systems in common human protein conformational disorders and provide an overview on current therapeutic interventions based on the modulation of the proteolytic systems.
细胞通过不断评估其每个蛋白质的质量来维持健康的蛋白质组。质量控制需要伴侣蛋白和蛋白水解系统的协调作用。伴侣蛋白识别蛋白质中的异常或不稳定构象，并经常协助它们恢复稳定性。但是，如果无法修复，则会将异常蛋白从细胞胞质溶胶中清除，以防止与其他蛋白发生不良相互作用或其组装成有毒的多聚复合物。自噬和泛素/蛋白酶体系统介导异常蛋白产物的完全降解。本文描述了这些蛋白水解系统及其对细胞质量控制的贡献。我们还评论了这些系统功能障碍在常见人类蛋白质构象疾病中的细胞后果，并概述了基于蛋白水解系统调节的当前治疗干预措施。
