The MLL4: Roles in cell differentiation, adipogenesis and cancer.

IF 5.6 2区医学 Q1 PHARMACOLOGY & PHARMACY

Biochemical pharmacology Pub Date : 2025-09-25 DOI:10.1016/j.bcp.2025.117371

Yu Zhang, Kaili Lv, Xubin Ma, Liang Wang, Yichao Xu

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引用次数: 0

Abstract

Epigenetic regulation of gene expression plays an important role in cellular biological processes. MLL4 (KMT2D), as a histone lysine methyltransferase, is responsible for the mono-, di- and tri- methylation of histone 3 lysine 4 (H3K4), and H3K4me1 at the super enhancer/enhancer or promoter regions usually couples with H3K27ac to promote the expression of many genes. The biology function of MLL4 in cell proliferation and adipogenesis has been widely reported. And silencing MLL4 prevent the development of obesity and fatty liver, making it a potential target. Furthermore, MLL4 is frequently mutated and loses the methyltransferase activity in multiple cancers. Dual functions of MLL4 in cancer have been reported due to the broad widely distribution of H3K4 in chromatin. The paradoxical function of MLL4 complicate it as the potential target of cancer therapy. Notably, MLL4 may be a biomarker for drug sensitivity or serves as a synthetic lethal gene for specific anti-cancer agents. In this review, we examine the protein structural features of MLL4, discuss the MLL4 action in cell differentiation, adipogenesis, and cancer, and identify current challenges for future investigations.

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MLL4：在细胞分化、脂肪形成和癌症中的作用。

基因表达的表观遗传调控在细胞生物学过程中起着重要作用。MLL4 （KMT2D）作为一种组蛋白赖氨酸甲基转移酶，负责组蛋白3赖氨酸4 （H3K4）的单、二、三甲基化，而位于超增强子/增强子或启动子区域的H3K4me1通常与H3K27ac偶联，促进许多基因的表达。MLL4在细胞增殖和脂肪形成中的生物学功能已被广泛报道。抑制MLL4可以防止肥胖和脂肪肝的发展，使其成为一个潜在的目标。此外，MLL4在多种癌症中经常发生突变并失去甲基转移酶活性。由于H3K4在染色质中的广泛分布，MLL4在癌症中的双重功能已被报道。MLL4的矛盾功能使其成为癌症治疗的潜在靶点。值得注意的是，MLL4可能是药物敏感性的生物标志物或作为特定抗癌药物的合成致死基因。在这篇综述中，我们研究了MLL4的蛋白质结构特征，讨论了MLL4在细胞分化、脂肪形成和癌症中的作用，并确定了未来研究的当前挑战。

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

Biochemical pharmacology 医学-药学

CiteScore

10.30

自引率

1.70%

发文量

420

审稿时长

17 days

期刊介绍： Biochemical Pharmacology publishes original research findings, Commentaries and review articles related to the elucidation of cellular and tissue function(s) at the biochemical and molecular levels, the modification of cellular phenotype(s) by genetic, transcriptional/translational or drug/compound-induced modifications, as well as the pharmacodynamics and pharmacokinetics of xenobiotics and drugs, the latter including both small molecules and biologics. The journal''s target audience includes scientists engaged in the identification and study of the mechanisms of action of xenobiotics, biologics and drugs and in the drug discovery and development process. All areas of cellular biology and cellular, tissue/organ and whole animal pharmacology fall within the scope of the journal. Drug classes covered include anti-infectives, anti-inflammatory agents, chemotherapeutics, cardiovascular, endocrinological, immunological, metabolic, neurological and psychiatric drugs, as well as research on drug metabolism and kinetics. While medicinal chemistry is a topic of complimentary interest, manuscripts in this area must contain sufficient biological data to characterize pharmacologically the compounds reported. Submissions describing work focused predominately on chemical synthesis and molecular modeling will not be considered for review. While particular emphasis is placed on reporting the results of molecular and biochemical studies, research involving the use of tissue and animal models of human pathophysiology and toxicology is of interest to the extent that it helps define drug mechanisms of action, safety and efficacy.