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通过基于结构的UHRF1结构域功能阐明对UHRF1介导的DNA甲基化的机制性见解(综述)

Mechanistic insights into UHRF1‑mediated DNA methylation by structure‑based functional clarification of UHRF1 domains (Review).

作者信息

Song Yiying, Liu Haiting, Xian Qingqing, Gui Chengzhi, Xu Mingjie, Zhou Yunying

机构信息

Department of Clinical Laboratory Diagnosis, Jinan Central Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.

Department of Critical Care Medicine, Jinan Zhangqiu Hospital of Traditional Chinese Medicine, Jinan, Shandong 250200, P.R. China.

出版信息

Oncol Lett. 2023 Nov 2;26(6):542. doi: 10.3892/ol.2023.14129. eCollection 2023 Dec.

Abstract

Epigenetic modification is crucial for transmitting genetic information, while abnormalities in DNA methylation modification are primarily associated with cancer and neurological diseases. As a multifunctional epigenetic modifier, ubiquitin like with PHD and ring finger domains 1 (UHRF1) mainly affects cell energy metabolism and cell cycle control. It also inhibits the transcription of tumor suppressor genes through DNA and/or histone methylation modifications, promoting the occurrence and development of cancer. Therefore, comprehensively understanding the molecular mechanism of the epigenetic modification of UHRF1 in tumors will help identify targets for inhibiting the expression and function of UHRF1. Notably, each domain of UHRF1 functions as a whole and differently. Thus, the abnormality of any domain can lead to a change in phenotype or disease. However, the specific regulatory mechanism and proteins of each domain have not been fully elucidated. The present review aimed to contribute to the study of the regulatory mechanism of UHRF1 to a greater extent in different cancers and provide ideas for drug research by clarifying the function of UHRF1 domains.

摘要

表观遗传修饰对于遗传信息的传递至关重要,而DNA甲基化修饰异常主要与癌症和神经疾病相关。作为一种多功能表观遗传修饰因子,含PHD和环指结构域1的泛素样蛋白(UHRF1)主要影响细胞能量代谢和细胞周期调控。它还通过DNA和/或组蛋白甲基化修饰抑制肿瘤抑制基因的转录,促进癌症的发生和发展。因此,全面了解UHRF1在肿瘤中的表观遗传修饰分子机制将有助于确定抑制UHRF1表达和功能的靶点。值得注意的是,UHRF1的每个结构域都作为一个整体发挥不同的功能。因此,任何一个结构域的异常都可能导致表型或疾病的改变。然而,每个结构域的具体调控机制和相关蛋白尚未完全阐明。本综述旨在通过阐明UHRF1结构域的功能,在更大程度上促进对UHRF1在不同癌症中调控机制的研究,并为药物研究提供思路。

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