去泛素化酶USP28在肿瘤中的作用及其抑制剂研究进展

Research progress on the roles and inhibitors of deubiquitinase USP28 in tumors

去泛素化酶(DUBs)是蛋白质泛素系统中一类重要的肽水解酶,对泛素化具有逆转和严格调控作用,在调节蛋白质稳定性、细胞信号转导等多种生物学过程中发挥重要功能。泛素特异性蛋白酶28(USP28)通过增强多种癌症相关蛋白的稳定性,参与癌症相关的多种信号途径,与结直肠癌、乳腺癌、肺癌、胰腺癌等多种肿瘤的进展密切相关。USP28已成为一个有吸引力的抗癌药物靶点,其抑制剂的开发取得了一定进展。本文对USP28的结构及其与底物的相互作用、USP28在肿瘤中的研究进展、USP28抑制剂的发现等方面进行了综述。

The deubiquitinases(DUBs),as the crucial peptidohydrolases in the ubiquitin system,can reverse and strictly regulate ubiquitination and play key roles in various biological processes,including the regulation of protein stability,cell signal transduction.Ubiquitin-specific protease 28(USP28)involves multiple cancer-related signaling pathways by enhancing the stability of various cancer-related proteins,and is closely associated with the progression of colorectal,breast cancer,lung carcinomas,and pancreatic cancer.USP28 has been considered as a promising drug target in anticancer therapy,and the development of USP28 inhibitors has made some progress.In this article,we review the structure of USP28 and its interaction with substrates,discuss the research progress of USP28 in cancers and summarize the development of USP28 inhibitors.