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TRIM 蛋白在肺癌中的作用机制、生物标志物和治疗靶点。

TRIM proteins in lung cancer: Mechanisms, biomarkers and therapeutic targets.

机构信息

Ecology and Health Institute, Hangzhou Vocational & Technical College, Hangzhou 310018, China.

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.

出版信息

Life Sci. 2021 Mar 1;268:118985. doi: 10.1016/j.lfs.2020.118985. Epub 2021 Jan 4.

Abstract

The tripartite motif (TRIM) family is defined by the presence of a Really Interesting New Gene (RING) domain, one or two B-box motifs and a coiled-coil region. TRIM proteins play key roles in many biological processes, including innate immunity, tumorigenesis, cell differentiation and ontogenetic development. Alterations in TRIM gene and protein levels frequently emerge in a wide range of tumors and affect tumor progression. As canonical E3 ubiquitin ligases, TRIM proteins participate in ubiquitin-dependent proteolysis of prominent components of the p53, NF-κB and PI3K/AKT signaling pathways. The occurrence of ubiquitylation events induced by TRIM proteins sustains internal balance between tumor suppressive and tumor promoting genes. In this review, we summarized the diverse mechanism of TRIM proteins responsible for the most common malignancy, lung cancer. Furthermore, we also discussed recent progress in both the diagnosis and therapeutics of tumors contributed by TRIM proteins.

摘要

三基序蛋白(TRIM)家族的定义是存在 Really Interesting New Gene(RING)结构域、一个或两个 B-box 基序和一个卷曲螺旋区。TRIM 蛋白在许多生物学过程中发挥着关键作用,包括先天免疫、肿瘤发生、细胞分化和个体发育。TRIM 基因和蛋白水平的改变经常出现在广泛的肿瘤中,并影响肿瘤的进展。作为典型的 E3 泛素连接酶,TRIM 蛋白参与 p53、NF-κB 和 PI3K/AKT 信号通路中重要成分的泛素依赖性蛋白水解。TRIM 蛋白诱导的泛素化事件的发生维持了肿瘤抑制基因和肿瘤促进基因之间的内部平衡。在这篇综述中,我们总结了 TRIM 蛋白在最常见的恶性肿瘤——肺癌中的多种作用机制。此外,我们还讨论了 TRIM 蛋白在肿瘤的诊断和治疗方面的最新进展。

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