Harris Timothy J, Trader Darci J
Department of Pharmaceutical Sciences, University of California Irvine California 92617 USA
Department of Chemistry, University of California Irvine California 92617 USA.
RSC Med Chem. 2025 Jan 1. doi: 10.1039/d4md00787e.
Degrons are short amino acid sequences that can facilitate the degradation of protein substrates. They can be classified as either ubiquitin-dependent or -independent based on their interactions with the ubiquitin proteasome system (UPS). These amino acid sequences are often found in exposed regions of proteins serving as either a tethering point for an interaction with an E3 ligase or initiating signaling for the direct degradation of the protein. Recent advancements in the protein degradation field have shown the therapeutic potential of both classes of degrons through leveraging their degradative effects to engage specific protein targets. This review explores what targeted protein degradation applications degrons can be used in and how they have inspired new degrader technology to target a wide variety of protein substrates.
降解决定子是能够促进蛋白质底物降解的短氨基酸序列。根据它们与泛素蛋白酶体系统（UPS）的相互作用，可将其分为依赖泛素或不依赖泛素两类。这些氨基酸序列通常位于蛋白质的暴露区域，要么作为与E3连接酶相互作用的连接点，要么启动蛋白质直接降解的信号。蛋白质降解领域的最新进展表明，通过利用这两类降解决定子的降解作用来作用于特定蛋白质靶点，它们具有治疗潜力。本综述探讨了降解决定子可用于哪些靶向蛋白质降解应用，以及它们如何激发了新的降解剂技术来靶向多种蛋白质底物。
