Abstract:
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 via 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.
摘要:
含有三方基序(TRIM)的蛋白质是一类E3泛素连接酶,这与肿瘤的发生和发展密切相关。它们可以通过调节肿瘤的各个方面发挥作用,如肿瘤增殖,转移,细胞凋亡与肿瘤治疗过程中耐药性的发展。TRIM家族蛋白的一些成员可以通过调节多种信号通路介导蛋白泛素化和染色体易位,像p53NF-κB,AKT,MAPK,Wnt/β-catenin等分子调控机制。TRIM的多结构域性质/多功能生物学作用意味着阻断一个功能或一个结构域可能不足以获得理想的治疗结果。因此,需要对TRIMs各个结构域的生物学功能有详细和系统的了解。本文主要阐述了它们在肿瘤发生和发展中的作用和潜在机制。它可能会掩盖TRIM在肿瘤治疗中的潜在靶向策略,特别是使用PROTACs。