Zhang Xiuzhen, Meng Tong, Cui Shuaishuai, Feng Ling, Liu Dongwu, Pang Qiuxiang, Wang Ping
School of Life Sciences, Shandong University of Technology, Zibo, China.
Tongji University Cancer Center, Shanghai Tenth People's Hospital of Tongji University, School of Medicine, Tongji University, Shanghai, China.
Front Oncol. 2021 Feb 11;10:621294. doi: 10.3389/fonc.2020.621294. eCollection 2020.
Ubiquitination, a crucial post-translation modification, regulates the localization and stability of the substrate proteins including nonhistone proteins. The ubiquitin-proteasome system (UPS) on nonhistone proteins plays a critical role in many cellular processes such as DNA repair, transcription, signal transduction, and apoptosis. Its dysregulation induces various diseases including cancer, and the identification of this process may provide potential therapeutic targets for cancer treatment. In this review, we summarize the regulatory roles of key UPS members on major nonhistone substrates in cancer-related processes, such as cell cycle, cell proliferation, apoptosis, DNA damage repair, inflammation, and T cell dysfunction in cancer. In addition, we also highlight novel therapeutic interventions targeting the UPS members (E1s, E2s, E3s, proteasomes, and deubiquitinating enzymes). Furthermore, we discuss the application of proteolysis-targeting chimeras (PROTACs) technology as a novel anticancer therapeutic strategy in modulating protein target levels with the aid of UPS.
泛素化是一种关键的翻译后修饰，可调节包括非组蛋白在内的底物蛋白的定位和稳定性。非组蛋白上的泛素-蛋白酶体系统（UPS）在许多细胞过程中发挥关键作用，如DNA修复、转录、信号转导和细胞凋亡。其失调会引发包括癌症在内的各种疾病，对这一过程的识别可能为癌症治疗提供潜在的治疗靶点。在本综述中，我们总结了关键UPS成员在癌症相关过程中对主要非组蛋白底物的调节作用，如细胞周期、细胞增殖、细胞凋亡、DNA损伤修复、炎症以及癌症中的T细胞功能障碍。此外，我们还重点介绍了针对UPS成员（E1、E2、E3、蛋白酶体和去泛素化酶）的新型治疗干预措施。此外，我们还讨论了靶向蛋白水解嵌合体（PROTAC）技术作为一种新型抗癌治疗策略，借助UPS调节蛋白靶点水平的应用。
