Multiple functions of the lysine methyltransferase KMT5a in cancer: potential targets for innovative therapies.

IF 4.4 2区医学 Q1 GENETICS & HEREDITY

Clinical Epigenetics Pub Date : 2025-09-29 DOI:10.1186/s13148-025-01980-3

Rosa Della Monica, Michela Buonaiuto, Mariella Cuomo, Davide Costabile, Claudio Schonauer, Giuseppe Catapano, Lorenzo Chiariotti, Roberta Visconti

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引用次数: 0

Abstract

Lysine methyltransferase 5a (KMT5a) plays a key role in the pathogenesis of many human diseases. Here, we review the diverse impacts of KMT5a activity on human cancer development and progression. First, KMT5a is the only Mammalian enzyme that specifically induces monomethylation of histone 4 (H4) on lysine 20, thus regulating chromatin organization and, in turn, the transcription of several oncogenes and tumor suppressor genes. KMT5a, by inducing H4 methylation, also critically establishes the choice between different pathways of DNA double-strand break repair, with important consequences for genomic instability and cancer origin. Finally, KMT5a also methylates lysine residues on nonhistone proteins, and KMT5a-induced methylation of key oncogenic and tumor suppressor proteins, including TP53, strongly affects cancer cell functions. Overall, KMT5a is overexpressed in a high percentage and wide variety of human cancers and has protumorigenic activity, which makes it a target for innovative therapy.

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赖氨酸甲基转移酶KMT5a在癌症中的多种功能：创新治疗的潜在靶点。

赖氨酸甲基转移酶5a （KMT5a）在许多人类疾病的发病机制中起着关键作用。在这里，我们回顾了KMT5a活性对人类癌症发生和进展的多种影响。首先，KMT5a是唯一一种特异性诱导赖氨酸20上组蛋白4 （H4）单甲基化的哺乳动物酶，从而调节染色质组织，进而调节几种癌基因和肿瘤抑制基因的转录。KMT5a通过诱导H4甲基化，也关键地建立了DNA双链断裂修复不同途径之间的选择，对基因组不稳定性和癌症起源具有重要影响。最后，KMT5a还能甲基化非组蛋白上的赖氨酸残基，KMT5a诱导的关键致癌蛋白和肿瘤抑制蛋白（包括TP53）的甲基化强烈影响癌细胞功能。总体而言，KMT5a在多种人类癌症中高比例过表达，并具有致瘤活性，这使其成为创新治疗的靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Epigenetics ONCOLOGY-

自引率

5.30%

发文量

150

期刊介绍： Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.