Zhang Yuxin, Zhang Wenzhou, Zheng Lufeng, Guo Qianqian
Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China.
School of Life Science and Technology, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, China.
Front Pharmacol. 2022 Sep 30;13:999380. doi: 10.3389/fphar.2022.999380. eCollection 2022.
Tripartite motif (TRIM) containing proteins are a class of E3 ubiquitin ligases, which are critically implicated in the occurrence and development of tumors. They can function through regulating various aspects of tumors, such as tumor proliferation, metastasis, apoptosis and the development of drug resistance during tumor therapy. Some members of TRIM family proteins can mediate protein ubiquitination and chromosome translocation modulating several signaling pathways, like p53, NF-κB, AKT, MAPK, Wnt/β-catenin and other molecular regulatory mechanisms. The multi-domain nature/multi-functional biological role of TRIMs implies that blocking just one function or one domain might not be sufficient to obtain the desired therapeutic outcome, therefore, a detailed and systematic understanding of the biological functions of the individual domains of TRIMs is required. This review mainly described their roles and underlying mechanisms in tumorigenesis and progression, and it might shade light on a potential targeting strategy for TRIMs in tumor treatment, especially using PROTACs.
含三联基序（TRIM）的蛋白质是一类E3泛素连接酶，在肿瘤的发生发展中起关键作用。它们可通过调节肿瘤的各个方面发挥作用，如肿瘤增殖、转移、凋亡以及肿瘤治疗期间耐药性的产生。TRIM家族蛋白的一些成员可介导蛋白质泛素化和染色体易位，调节多种信号通路，如p53、NF-κB、AKT、MAPK、Wnt/β-连环蛋白等分子调控机制。TRIMs的多结构域性质/多功能生物学作用意味着仅阻断一种功能或一个结构域可能不足以获得理想的治疗效果，因此，需要对TRIMs各个结构域的生物学功能进行详细而系统的了解。本综述主要描述了它们在肿瘤发生和进展中的作用及潜在机制，可能为TRIMs在肿瘤治疗中的潜在靶向策略提供思路，尤其是使用蛋白水解靶向嵌合体（PROTACs）。
