文章：

TRIM蛋白与癌症

TRIM proteins and cancer

原文发布日期：2011-10-07

DOI: 10.1038/nrc3139

类型: Review Article

开放获取: 否

要点：

1. The family of tripartite motif (TRIM)-containing proteins is defined as a subfamily of the RING type E3 ubiquitin ligase family and contains more than 70 members in humans and mice. TRIM family proteins are involved in a broad range of biological processes, including transcriptional regulation, cell growth, apoptosis, development and tumorigenesis.
2. Several TRIM proteins are involved in the regulation of nuclear receptors. The promyelocytic leukaemia (PML) gene encodes TRIM19 and is involved in the t(15;17) translocation that is specific for acute promyelocytic leukaemia (APL). TRIM19 is localized in PML-nuclear bodies (PML-NBs) in the nucleus and regulates the response to various cellular stresses, DNA repair and viral infection.
3. TRIM24 (also known as TIF1α) regulates several nuclear receptors, including, retinoic acid receptor-α (RARα), the thyroid receptor and the oestrogen receptors (ERs). TRIM24 is a potent liver-specific tumour suppressor in mice and attenuates RARα-mediated transcription. TRIM28 (also known as TIF1β and KAP1) is highly expressed in many cancers and contributes to p53 inactivation.
4. TRIM proteins, including TRIM24 and TRIM22, are also involved in p53 regulation. TRIM13 overexpression causes increased expression of p53, resulting in the induction of apoptosis. TRIM29 (also known as ATDC) regulates p53 through its interaction with TIP60. TRIM29 expression correlates with a poor prognosis in gastric cancer.
5. Other TRIMs, such as TRIM32, TRIM8 and TRIM40, have been associated with specific tumorigenic pathways.
6. Further work using biochemical approaches as well as genetic knock-in and knockout experiments in mice are needed to understand the full contribution of specific TRIM proteins to tumour development and progression.

要点翻译：

1. 含有三联基序（TRIM）的蛋白家族被定义为RING型E3泛素连接酶家族的一个亚族，在人类和小鼠中包含70多个成员。TRIM家族蛋白参与广泛的生物学过程，包括转录调控、细胞生长、凋亡、发育和肿瘤发生。
2. 多种TRIM蛋白参与核受体的调控。早幼粒细胞白血病（PML）基因编码TRIM19，并参与急性早幼粒细胞白血病（APL）特异性的t(15;17)染色体易位。TRIM19定位于细胞核内的PML核体（PML-NBs），调控多种细胞应激反应、DNA修复和病毒感染。
3. TRIM24（亦称TIF1α）调控多种核受体，包括视黄酸受体α（RARα）、甲状腺激素受体和雌激素受体（ERs）。TRIM24是小鼠体内一种有效的肝脏特异性肿瘤抑制因子，并能减弱RARα介导的转录。TRIM28（亦称TIF1β和KAP1）在多种癌症中高表达，并参与p53的失活过程。
4. TRIM蛋白（包括TRIM24和TRIM22）也参与p53的调控。TRIM13过表达会导致p53表达增加，从而诱导细胞凋亡。TRIM29（亦称ATDC）通过与TIP60相互作用来调控p53。TRIM29的表达与胃癌患者的不良预后相关。
5. 其他TRIM蛋白，如TRIM32、TRIM8和TRIM40，也与特定的致瘤通路相关。
6. 需要通过生物化学方法以及小鼠基因敲入和敲除实验进行进一步研究，以全面了解特定TRIM蛋白在肿瘤发生和发展中的作用。

英文摘要：

Emerging clinical evidence shows that the deregulation of ubiquitin-mediated degradation of oncogene products or tumour suppressors is likely to be involved in the aetiology of carcinomas and leukaemias. Recent studies have indicated that some members of the tripartite motif (TRIM) proteins (one of the subfamilies of the RING type E3 ubiquitin ligases) function as important regulators for carcinogenesis. This Review focuses on TRIM proteins that are involved in tumour development and progression.

摘要翻译： 

新兴临床证据表明，癌基因产物或肿瘤抑制因子的泛素介导降解失调可能与癌和白血病的发病机制有关。近期研究表明，三部分基序（TRIM）蛋白家族（RING型E3泛素连接酶亚家族之一）的部分成员在致癌过程中发挥重要调控作用。本文综述聚焦于参与肿瘤发生与进展的TRIM蛋白。

原文链接：

TRIM proteins and cancer