Abstract

Protein ubiquitylation plays important roles in many biological activities. Protein ubiquitylation is a unique process that is mainly controlled by ubiquitin ligases. The ubiquitin-proteasome system (UPS) is the main process to degrade short-lived and unwanted proteins in eukaryotes. Many components in the UPS are attractive drug targets. Recent studies indicated that ubiquitin ligases can be employed as tools in proteolysis-targeting chimeras (PROTACs) for drug discovery. In this review article, we will discuss the recent progress of the application of ubiquitin ligases in the PROTAC drug design. We will also discuss advantages and existing problems of PROTACs. Moreover, we will propose a few principles for selecting ubiquitin ligases in PROTAC applications.

中文翻译：

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泛素连接酶在PROTAC药物设计中的应用。

摘要

蛋白质泛素化在许多生物学活动中起重要作用。蛋白质泛素化是一个独特的过程，主要受泛素连接酶控制。泛素-蛋白酶体系统（UPS）是降解真核生物中短暂和不需要的蛋白质的主要过程。UPS中的许多组件都是有吸引力的药物目标。最近的研究表明，泛素连接酶可用作蛋白水解靶向嵌合体（PROTAC）中的工具，用于发现药物。在这篇综述文章中，我们将讨论泛素连接酶在PROTAC药物设计中的最新应用进展。我们还将讨论PROTAC的优势和存在的问题。此外，我们将提出一些在PROTAC应用中选择泛素连接酶的原则。