Department of Cell and Chemical Biology, Oncode Institute , Leiden University Medical Center , Leiden , The Netherlands.
Department of Cell and Chemical Biology , Leiden University Medical Center , Leiden , The Netherlands.
ACS Chem Biol. 2019 Nov 15;14(11):2389-2395. doi: 10.1021/acschembio.9b00402. Epub 2019 Aug 5.
SUMOylation is a reversible and highly dynamic post-translational modification of target proteins by small ubiquitin-like modifiers (SUMO). It is orchestrated by SUMO-activating, -conjugating, and -ligating enzymes in a sequential manner and is important in regulating a myriad of predominantly nuclear processes. DeSUMOylation is achieved by SUMO-specific proteases (SENPs). Deregulation of SUMOylation and deSUMOylation results in cellular dysfunction and is linked to various diseases, including cancer. In recent years, SENPs have emerged as potential therapeutic targets. In this review, we will describe the inhibitors and activity-based probes of SENPs. Furthermore, we will summarize the biochemical assays available for evaluating the activity of SENPs to identify inhibitors.
SUMOylation 是一种通过小泛素样修饰物 (SUMO) 对靶蛋白进行的可逆且高度动态的翻译后修饰。它由 SUMO-激活酶、SUMO-连接酶和 SUMO-连接酶依次进行调控，在调节众多主要核过程中非常重要。去 SUMOylation 是通过 SUMO 特异性蛋白酶 (SENPs) 实现的。SUMOylation 和去 SUMOylation 的失调会导致细胞功能障碍，并与各种疾病相关，包括癌症。近年来，SENPs 已成为潜在的治疗靶点。在这篇综述中，我们将描述 SENPs 的抑制剂和基于活性的探针。此外，我们将总结用于评估 SENPs 活性以鉴定抑制剂的生化测定方法。
