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 …
Cryo-EM structure of the human MLL1 core complex bound to the ...
2019年12月5日 · Here we report the single-particle cryo-electron microscopy (cryo-EM) structure of the NCP-bound human MLL1 core complex. We show that the MLL1 core complex anchors to the NCP via the conserved...
Menin–MLL1 Interaction Small Molecule Inhibitors: A Potential ...
Encoded by the MEN1 gene, menin protein is a fusion protein that is essential for the oncogenic transformation of mixed-lineage leukemia (MLL) and leads to acute leukemia (AL). Therefore, accumulating evidence has demonstrated that inhibition of the ...
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 · 陈勇研究组的前期工作揭示了RBBP5中的一段保守多肽（RBBP5 AS+ABM）调控MLL家族蛋白活性的结构基础和分子机制（Nature, 2016），但全长RBBP5蛋白参与MLL1甲基转移酶复合物的组装和活性调控的分子机制仍值得深入研究。 在陈勇研究员的指导下，博士研究生韩建明、李婷婷等研究人员首次揭示了RBBP5存在内部的相互作用，并且这种相互作用会显著增强MLL1复合物的活性。 为找出该蛋白内部发生相互作用的关键氨基酸，研究人员解析了RBBP5 …
【经验】MLL1抑制剂MM-102的研究进展 - 丁香园论坛 - DXY.cn
MM-102，作为MLL1的模拟肽，展现了与WDR5的高亲和性，相应的IC50和Ki分别为2.9nM和 1nM。在转染了MLL1-AF9的鼠源细胞中，MM-102特异性的降低了两个重要的MLL1靶基因（HoxA9andMeis-1）的表达，这两个基因是MLL1介导的白血病形成所必须的。
Targeting MLL1 H3K4 Methyltransferase Activity in Mixed …
MM-401 is able to specifically inhibit MLL1 activity by blocking MLL1-WDR5 interaction and thus the complex assembly. This targeting strategy does not affect other mixed-lineage leukemia (MLL) family histone methyltransferases (HMTs), revealing a unique regulatory feature for …
Non-canonical MLL1 activity regulates centromeric phase ... - Nature
2023年11月9日 · These results demonstrate a non-redundant function of MLL1 in regulating inner centromere liquid condensates and genome stability via a non-canonical enzymatic activity. The MLL/KMT2 family...
Menin–MLL1 Interaction Small Molecule Inhibitors: A Potential
2023年3月28日 · Therefore, accumulating evidence has demonstrated that inhibition of the high-affinity relationship between menin and mixed-lineage leukemia 1 (MLL1 and KMT2A) is an effective treatment for MLL-rearranged (MLL-r) leukemia in vitro and in vivo.
Elucidating the role of MLL1 nsSNPs: Structural and functional ...
2024年10月15日 · Our research provides a comprehensive assessment of nsSNPs’ impact in the MLL1 protein structure and function and consequently on leukemia development, suggesting potential avenues for personalized treatment, early detection, improved prognosis, and a deeper understanding of hematological malignancy genesis.
精准院黄晶课题组揭示核小体结构对组蛋白修饰酶复合物的酶活调 …
2019年9月4日 · MLL复合物是调控基因转录激活的关键表观遗传因子，参与造血系统发育、成脂分化、个体发育等重要生理过程。其基因突变与白血病、Kabuki综合症、自闭症及多种实体肿瘤的病理机制密切相关。