Protein degradation is critical for proteostasis, and the addition of polyubiquitin chains to a substrate is necessary for its recognition by the 26S proteasome. Therapeutic intervention in the ubiquitin proteasome system has implications ranging from cancer to neurodegeneration. Novel screening methods and chemical biology tools for targeting E1-activating, E2-conjugating and deubiquitinating enzymes will be discussed in this review. Approaches for targeting E3 ligase-substrate interactions as well as the proteasome will also be covered, with a focus on recently described approaches.

中文翻译：

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针对泛素蛋白酶体系统的潜在发现和化学生物学方法

蛋白质降解对于蛋白稳态至关重要，而将聚泛素链添加至底物对于被26S蛋白酶体识别是必需的。泛素蛋白酶体系统的治疗干预具有从癌症到神经退行性变的影响。本文将讨论针对E1活化，E2缀合和去泛素化酶的新型筛选方法和化学生物学工具。靶向E3连接酶-底物相互作用以及蛋白酶体的方法也将涵盖在内，重点是最近描述的方法。