Park Hong-Beom, Baek Kwang-Hyun
Department of Convergence, CHA University, Gyeonggi-Do 13488, Republic of Korea.
Department of Convergence, CHA University, Gyeonggi-Do 13488, Republic of Korea; International Ubiquitin Center(,) CHA University, Gyeonggi-Do 13488, Republic of Korea.
Biochim Biophys Acta Rev Cancer. 2023 Nov;1878(6):188992. doi: 10.1016/j.bbcan.2023.188992. Epub 2023 Sep 27.
The ubiquitin-proteasome system (UPS) is an essential protein quality controller for regulating protein homeostasis and autophagy. Ubiquitination is a protein modification process that involves the binding of one or more ubiquitins to substrates through a series of enzymatic processes. These include ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), and ubiquitin ligases (E3). Conversely, deubiquitination is a reverse process that removes ubiquitin from substrates via deubiquitinating enzymes (DUBs). Dysregulation of ubiquitination-related enzymes can lead to various human diseases, including cancer, through the modulation of protein ubiquitination. The most structurally and functionally studied DUB is the ubiquitin-specific protease 7 (USP7). Both the TRAF and UBL domains of USP7 are known to bind to the [P/A/E]-X-X-S or K-X-X-X-K motif of substrates. USP7 has been shown to be involved in cancer pathogenesis by binding with numerous substrates. Recently, a novel substrate of USP7 was discovered through a systemic analysis of its binding motif. This review summarizes the currently discovered substrates and cellular functions of USP7 in cancer and suggests putative substrates of USP7 through a comprehensive systemic analysis.
泛素-蛋白酶体系统（UPS）是调节蛋白质稳态和自噬的重要蛋白质质量控制机制。泛素化是一种蛋白质修饰过程，涉及通过一系列酶促反应将一个或多个泛素与底物结合。这些酶包括泛素激活酶（E1）、泛素结合酶（E2）和泛素连接酶（E3）。相反，去泛素化是一个通过去泛素化酶（DUBs）从底物上去除泛素的反向过程。泛素化相关酶的失调可通过调节蛋白质泛素化导致包括癌症在内的各种人类疾病。在结构和功能上研究最多的DUB是泛素特异性蛋白酶7（USP7）。已知USP7的TRAF和UBL结构域均与底物的[P/A/E]-X-X-S或K-X-X-X-K基序结合。已证明USP7通过与多种底物结合参与癌症发病机制。最近，通过对其结合基序的系统分析发现了USP7的一种新底物。本综述总结了目前在癌症中发现的USP7底物和细胞功能，并通过全面的系统分析提出了USP7的推定底物。
