UHRF1 的翻译后修饰在癌症中的作用。

IF 4.2 2区 生物学 Q1 GENETICS & HEREDITY
Lili Gu, Yongming Fu, Xiong Li
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引用次数: 0

摘要

UHRF1是RING-finger型E3泛素连接酶家族的成员,是一种具有五个结构域的表观遗传调控因子。它参与调控一系列生物功能,如 DNA 复制、DNA 甲基化和 DNA 损伤修复。此外,在十多种癌症类型中都观察到了 UHRF1 的异常过表达,这表明 UHRF1 是一种典型的癌基因。UHRF1 的过表达通过 DNMT1 介导的 DNA 甲基化抑制了 CDKN2A、BRCA1 和 CDH1 等肿瘤抑制基因的转录。除了上游转录因子调控基因转录外,翻译后修饰(PTM)也是导致 UHRF1 在癌症组织中异常过表达的原因之一。PTM类型包括磷酸化、乙酰化、甲基化和泛素化,它们调控蛋白质的稳定性、组蛋白甲基转移酶的活性、细胞内定位以及与结合伙伴的相互作用。最近,有报道称 UHRF1 存在几种新的 PTM 类型,但其具体机制仍不清楚。本综述总结了 UHRF1 的 PTM 类型及其生物学功能。深入了解 UHRF1 的这些关键机制对于未来开发新型 UHRF1 靶向抗癌治疗策略至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Roles of post-translational modifications of UHRF1 in cancer.

UHRF1 as a member of RING-finger type E3 ubiquitin ligases family, is an epigenetic regulator with five structural domains. It has been involved in the regulation of a series of biological functions, such as DNA replication, DNA methylation, and DNA damage repair. Additionally, aberrant overexpression of UHRF1 has been observed in over ten cancer types, indicating that UHRF1 is a typical oncogene. The overexpression of UHRF1 repressed the transcription of such tumor-suppressor genes as CDKN2A, BRCA1, and CDH1 through DNMT1-mediated DNA methylation. In addition to the upstream transcription factors regulating gene transcription, post-translational modifications (PTMs) also contribute to abnormal overexpression of UHRF1 in cancerous tissues. The types of PTM include phosphorylation, acetylation, methylationand ubiquitination, which regulate protein stability, histone methyltransferase activity, intracellular localization and the interaction with binding partners. Recently, several novel PTM types of UHRF1 have been reported, but the detailed mechanisms remain unclear. This comprehensive review summarized the types of UHRF1 PTMs, as well as their biological functions. A deep understanding of these crucial mechanisms of UHRF1 is pivotal for the development of novel UHRF1-targeted anti-cancer therapeutic strategies in the future.

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来源期刊
Epigenetics & Chromatin
Epigenetics & Chromatin GENETICS & HEREDITY-
CiteScore
7.00
自引率
0.00%
发文量
35
审稿时长
1 months
期刊介绍: Epigenetics & Chromatin is a peer-reviewed, open access, online journal that publishes research, and reviews, providing novel insights into epigenetic inheritance and chromatin-based interactions. The journal aims to understand how gene and chromosomal elements are regulated and their activities maintained during processes such as cell division, differentiation and environmental alteration.
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