The ubiquitin-proteasome pathway has emerged as a central player in the regulation of several diverse cellular processes. Here, we describe the important components of this complex biochemical machinery as well as several important cellular substrates targeted by this pathway and examples of human diseases resulting from defects in various components of the ubiquitin-proteasome pathway. In addition, this review covers the chemistry of synthetic and natural proteasome inhibitors, emphasizing their mode of actions toward the 20S proteasome. Given the importance of proteasome-mediated protein degradation in various intracellular processes, inhibitors of this pathway will continue to serve as both molecular probes of major cellular networks as well as potential therapeutic agents for various human diseases.

中文翻译：

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泛素-蛋白酶体途径和蛋白酶体抑制剂。

泛素-蛋白酶体途径已经成为调节几种不同细胞过程的中心参与者。在这里，我们描述了这种复杂的生化机制的重要组成部分，以及该途径靶向的几种重要细胞底物，以及由泛素-蛋白酶体途径的各种组成部分缺陷导致的人类疾病的实例。此外，本综述涵盖了合成和天然蛋白酶体抑制剂的化学性质，强调了它们对20S蛋白酶体的作用方式。考虑到蛋白酶体介导的蛋白质降解在各种细胞内过程中的重要性，该途径的抑制剂将继续充当主要细胞网络的分子探针以及各种人类疾病的潜在治疗剂。