The role of TRIM family proteins in the regulation of cancer stem cell self-renewal,STEM CELLS

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The role of TRIM family proteins in the regulation of cancer stem cell self-renewal
STEM CELLS ( IF 4.0 ) Pub Date : 2019-11-09 , DOI: 10.1002/stem.3109
Anna Maria Jaworska ₁ , Nikola Agata Wlodarczyk ₂ , Andrzej Mackiewicz _{1,

3} , Patrycja Czerwinska _{1,

3}

Affiliation

The tripartite‐motif (TRIM) family of proteins represents one of the largest classes of putative single protein RING‐finger E3 ubiquitin ligases. The members of this family are characterized by an N‐terminal TRIM motif containing one RING‐finger domain, one or two zinc‐finger domains called B boxes (B1 box and B2 box), and a coiled‐coil region. The TRIM motif can be found in isolation or in combination with a variety of C‐terminal domains, and based on C‐terminus, TRIM proteins are classified into 11 distinct groups. Because of the complex nature of TRIM proteins, they are implicated in a variety of cellular functions and biological processes, including regulation of cell proliferation, cell division and developmental processes, cancer transformation, regulation of cell metabolism, autophagocytosis, modification of chromatin status, regulation of gene transcription, post‐translational modifications, and interactions with pathogens. Here, we demonstrate the specific activities of TRIM family proteins that contribute to the cancer stem cell phenotype. A growing body of evidence demonstrates that several TRIM members guarantee the acquisition of stem cell properties and the ability to sustain stem‐like phenotype by cancer cells using distinct mechanisms. For other members, further work is needed to understand their full contribution to stem cell self‐renewal. Identification of TRIM proteins that possess the potential to serve as therapeutic targets may result in the development of new therapeutic strategies. Finally, these strategies may result in the disruption of the machinery of stemness acquisition, which may prevent tumor growth, progression, and overcome the resistance to anticancer therapies.

中文翻译：

TRIM家族蛋白在调控肿瘤干细胞自我更新中的作用

三方基序 (TRIM) 蛋白质家族代表了最大的一类单蛋白 RING-finger E3 泛素连接酶。该家族成员的特点是一个 N 端 TRIM 基序包含一个环指结构域、一个或两个称为 B 盒（B1 盒和 B2 盒）的锌指结构域和一个卷曲螺旋区域。TRIM 基序可以单独存在或与各种 C 端结构域结合使用，并且基于 C 端，TRIM 蛋白分为 11 个不同的组。由于 TRIM 蛋白的复杂性质，它们涉及多种细胞功能和生物学过程，包括细胞增殖的调节、细胞分裂和发育过程、癌症转化、细胞代谢的调节、自噬、染色质状态的改变、基因转录的调控、翻译后修饰以及与病原体的相互作用。在这里，我们展示了有助于癌症干细胞表型的 TRIM 家族蛋白的特定活性。越来越多的证据表明，几个 TRIM 成员保证了获得干细胞特性和癌细胞使用不同机制维持干细胞样表型的能力。对于其他成员，需要进一步的工作来了解他们对干细胞自我更新的全部贡献。鉴定具有作为治疗靶标潜力的 TRIM 蛋白可能会导致新治疗策略的开发。最后，这些策略可能会导致干细胞获得机制的破坏，这可能会阻止肿瘤的生长、进展、

更新日期：2019-11-09

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