Wu Wangxi, Yang Jinyu, Yu Tian, Zou Zhuoling, Huang Xuan
The National Engineering Research Center for Bioengineering Drugs and the Technologies, Jiangxi Provincial Key Laboratory of Bioengineering Drugs, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang 330031, China.
The Queen Mary School, Jiangxi Medical College, Nanchang University, Nanchang 330031, China.
Cells. 2024 Dec 19;13(24):2107. doi: 10.3390/cells13242107.
Tripartite motif (TRIM) family proteins, distinguished by their N-terminal region that includes a Really Interesting New Gene (RING) domain with E3 ligase activity, two B-box domains, and a coiled-coil region, have been recognized as significant contributors in carcinogenesis, primarily via the ubiquitin-proteasome system (UPS) for degrading proteins. Mechanistically, these proteins modulate a variety of signaling pathways, including Wnt/β-catenin, PI3K/AKT, and TGF-β/Smad, contributing to cellular regulation, and also impact cellular activities through non-signaling mechanisms, including modulation of gene transcription, protein degradation, and stability via protein-protein interactions. Currently, growing evidence indicates that TRIM proteins emerge as potential regulators in gastric cancer, exhibiting both tumor-suppressive and oncogenic roles. Given their critical involvement in cellular processes and the notable challenges of gastric cancer, exploring the specific contributions of TRIM proteins to this disease is necessary. Consequently, this review elucidates the roles and mechanisms of TRIM proteins in gastric cancer, emphasizing their potential as therapeutic targets and prognostic factors.
三联基序（TRIM）家族蛋白以其N端区域为特征，该区域包含具有E3连接酶活性的真核生物中一个新的有趣基因（RING）结构域、两个B盒结构域和一个卷曲螺旋区域，主要通过泛素-蛋白酶体系统（UPS）降解蛋白质，已被认为是致癌过程中的重要因素。从机制上讲，这些蛋白调节多种信号通路，包括Wnt/β-连环蛋白、PI3K/AKT和TGF-β/Smad通路，参与细胞调节，还通过非信号机制影响细胞活动，包括通过蛋白质-蛋白质相互作用调节基因转录、蛋白质降解和稳定性。目前，越来越多的证据表明，TRIM蛋白在胃癌中作为潜在的调节因子出现，兼具肿瘤抑制和致癌作用。鉴于它们在细胞过程中的关键作用以及胃癌面临的显著挑战，探索TRIM蛋白对这种疾病的具体贡献是必要的。因此，本综述阐明了TRIM蛋白在胃癌中的作用和机制，强调了它们作为治疗靶点和预后因素的潜力。
