<br>MLL2 (KMT2B) 蛋白赖氨酸甲基转移酶的结构、活性和功能,Life

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MLL2 (KMT2B) 蛋白赖氨酸甲基转移酶的结构、活性和功能
Life ( IF 2.991 ) Pub Date : 2021-08-12 , DOI: 10.3390/life11080823
Alexia Klonou ₁ , Sarantis Chlamydas _{1,

2} , Christina Piperi ₁

Affiliation

混合谱系白血病 2 (MLL2) 蛋白也称为 KMT2B，属于哺乳动物组蛋白 H3 赖氨酸 4 (H3K4) 甲基转移酶家族。它是一种由 2715 个氨基酸组成的大蛋白，广泛表达于成人组织中，是 MLL1 蛋白的旁系同源物。 MLL2 包含负责甲基转移酶活性的特征性 C 端 SET 结构域，并与 WRAD（WDR5、RbBP5、ASH2L 和 DPY30）、宿主细胞因子 1/2 (HCF 1/2) 和 Menin 形成蛋白质复合物。 MLL2 复合体负责特定基因启动子和附近的顺式调节位点上的 H3K4 三甲基化 (H3K4me3)，调节二价发育基因以及干细胞和生殖细胞分化基因集。此外，MLL2 在发育中发挥着关键作用， Mll2的种系缺失与早期生长迟缓、神经管缺陷和导致胚胎死亡的细胞凋亡有关。它还参与随意运动的控制和儿童早期肌张力障碍的发病机制。此外，MLL2 的促肿瘤功能已在多种癌症类型中被发现，包括结直肠癌、肝细胞癌、滤泡癌和神经胶质瘤。在这篇综述中，我们讨论了 MLL2 甲基转移酶的主要结构和功能方面，特别强调转录机制、基因调控以及与疾病的关联。

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Structure, Activity and Function of the MLL2 (KMT2B) Protein Lysine Methyltransferase

The Mixed Lineage Leukemia 2 (MLL2) protein, also known as KMT2B, belongs to the family of mammalian histone H3 lysine 4 (H3K4) methyltransferases. It is a large protein of 2715 amino acids, widely expressed in adult human tissues and a paralog of the MLL1 protein. MLL2 contains a characteristic C-terminal SET domain responsible for methyltransferase activity and forms a protein complex with WRAD (WDR5, RbBP5, ASH2L and DPY30), host cell factors 1/2 (HCF 1/2) and Menin. The MLL2 complex is responsible for H3K4 trimethylation (H3K4me3) on specific gene promoters and nearby cis-regulatory sites, regulating bivalent developmental genes as well as stem cell and germinal cell differentiation gene sets. Moreover, MLL2 plays a critical role in development and germ line deletions of Mll2 have been associated with early growth retardation, neural tube defects and apoptosis that leads to embryonic death. It has also been involved in the control of voluntary movement and the pathogenesis of early stage childhood dystonia. Additionally, tumor-promoting functions of MLL2 have been detected in several cancer types, including colorectal, hepatocellular, follicular cancer and gliomas. In this review, we discuss the main structural and functional aspects of the MLL2 methyltransferase with particular emphasis on transcriptional mechanisms, gene regulation and association with diseases.

更新日期：2021-08-12

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