KMT2A - Wikipedia
Histone-lysine N-methyltransferase 2A, also known as acute lymphoblastic leukemia 1 (ALL-1), myeloid/lymphoid or mixed-lineage leukemia 1 (MLL1), or zinc finger protein HRX (HRX), is an enzyme that in humans is encoded by the KMT2A gene.
科学家揭示MLL家族蛋白甲基转移酶活性调节的分子机制
MLL家族蛋白（MLL1/2/3/4，SET1A/B）是一类特异性针对H3K4的甲基转移酶，其甲基转移酶活性依赖于C末端的一个保守的SET结构域。 前人实验发现，MLL家族蛋白与其他具有SET结构域的甲基转移酶不同，它行使功能需要多个辅助蛋白WDR5、RBBP5、ASH2L组成复合体才能有效完成甲基化修饰过程。 由于缺乏原子分辨率的结构，整个复合物如何有效实现甲基化修饰一直处于争论之中，MLL家族蛋白是否采用了相同或者不同的活性调控机制也是不得而知。
陈勇研究组揭示MLL1甲基转移酶复合物的组装和活性调控新机制
2019年9月27日 · 其中研究最多的是混合谱系白血病蛋白MLL1 (Mixed Lineage Leukemia 1)，它能与70多种基因发生重排形成融合蛋白。 产生的MLL1 融合蛋白因其复合物组装和酶活异常，造成机体的造血功能障碍而引发白血病。
MLL1 and MLL1 fusion proteins have distinct functions in …
2016年5月17日 · Mixed lineage leukemia protein-1 (MLL1) has a critical role in human MLL1 rearranged leukemia (MLLr) and is a validated therapeutic target. However, its role in...
Mol Cell：陈勇团队等揭示MLL家族蛋白具有不同产物特异性的分 …
2022年9月15日 · 通过测定不同MLL复合物催化底物发生单、双、三甲基化的速率常数k1，k2，k3及比较各级反应速率之间的差距，研究人员将MLL1/MLL2定义为非连续的二甲基转移酶，MLL3/MLL4定义为单甲基转移酶，而SET1A/SET1B是非连续的三甲基转移酶。 利用这些测活系统，研究人员进一步发现产物特异性主要由最小的MLL-RBBP5-ASH2L三元复合物决定，其他的亚基如DPY30等主要影响酶活速率而不影响产物特异性。 为了进一步探讨产物特异性的分子机 …
Non-canonical MLL1 activity regulates centromeric phase ... - Nature
2023年11月9日 · Our results show a potential therapeutic strategy of targeting MLL1 in a subset of hepatocellular carcinoma (HCC) that exhibits a high level of chromosomal instability. We performed two...
Structure, function and inhibition of critical protein–protein ...
2021年4月6日 · Mixed lineage leukemia 1 (MLL1, also known as MLL or KMT2A) is an important transcription factor and histone-H3 lysine-4 (H3K4) methyltransferase. It is a master regulator for transcription of important genes (e.g., Hox genes) for embryonic development and hematopoiesis. However, it is largely dispensable in matured cells.
The histone lysine methyltransferase MLL1 regulates the …
2024年5月28日 · Here, we show that T cell-specific deletion of the lysine methyltransferase MLL1 results in a spontaneous lymphocyte proliferation phenotype in aged mice without disturbing the development of conventional T cells and Tregs. Treg-specific MLL1 ablation leads to a systemic autoimmune disease associated with Treg dysfunction.
Structural basis of nucleosome recognition and modification by …
2019年9月4日 · Methyltransferases of the mixed-lineage leukaemia (MLL) family—which include MLL1, MLL2, MLL3, MLL4, SET1A and SET1B—implement methylation of histone H3 on lysine 4 (H3K4), and have critical ...
MLL1 and MLL1 fusion proteins have distinct functions in
2016年5月17日 · Mixed lineage leukemia protein-1 (MLL1) has a critical role in human MLL1 rearranged leukemia (MLLr) and is a validated therapeutic target. However, its role in regulating global gene expression in MLLr cells, as well as its interplay with MLL1 fusion proteins remains unclear. Here we show that desp …