Targeting protein-protein interaction between MLL1 and reciprocal proteins for leukemia therapy
Targeting protein-protein interaction between MLL1 and reciprocal proteins for leukemia therapy
复制标题
靶向 MLL1 和互补蛋白之间的蛋白质-蛋白质相互作用用于白血病治疗
DOI：
10.1016/j.bmc.2017.11.045
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发表时间：
2017
影响因子：
3.5
通讯作者：
Xiaoke Guo
中科院分区：
文献类型：
--
作者：
Zhihui Wang;Dongdong Li;Weilin Chen;Qidong You;Xiaoke Guo
混合谱系白血病蛋白1（MLL 1）是一种赖氨酸甲基转移酶，主要调控组蛋白H3赖氨酸4（H3 K4）的甲基化，参与造血干细胞（HSC）的自我更新。MLL 1基因与伴侣基因融合，导致MLL 1融合蛋白（MLL 1-FP）的产生，这在急性白血病中经常被检测到。在白血病的发生发展过程中，许多蛋白质与MLL 1相互作用形成多蛋白复合物，参与H3 K4甲基化的异常调控，导致同源异型盒（HOX）簇基因的过度表达，从而导致白血病的发生。因此，破坏MLL 1和互补蛋白之间的相互作用被认为是白血病的新治疗策略。本文综述了MLL 1与其对应蛋白之间潜在的蛋白质-蛋白质相互作用（PPIs），并对MLL 1 PPIs的抑制剂进行了综述。对MLL 1质子泵抑制剂治疗白血病的药敏性进行了讨论。
The mixed lineage leukemia protein-1 (MLL1), as a lysine methyltransferase, predominantly regulates the methylation of histone H3 lysine 4 (H3K4) and functions in hematopoietic stem cell (HSC) self-renewal. MLL1 gene fuses with partner genes that results in the generation of MLL1 fusion proteins (MLL1-FPs), which are frequently detected in acute leukemia. In the progress of leukemogenesis, a great deal of proteins cooperate with MLL1 to form multiprotein complexes serving for the dysregulation of H3K4 methylation, the overexpression of homeobox (HOX) cluster genes, and the consequent generation of leukemia. Hence, disrupting the interactions between MLL1 and the reciprocal proteins has been considered to be a new treatment strategy for leukemia. Here, we reviewed potential protein-protein interactions (PPIs) between MLL1 and its reciprocal proteins, and summarized the inhibitors to target MLL1 PPIs. The druggability of MLL1 PPIs for leukemia were also discussed.