组蛋白甲基转移酶MLL1的结构与功能研究进展

Progress in Structural and Functional Studies of Histone Methyltransferase MLL1

组蛋白甲基转移酶MLL1因其基因易位重排所引起的混合系白血病(mixed lineage leukemia)而得名。MLL1蛋白在基因调控、细胞增殖、生长分化等正常生理功能中发挥着重要作用,染色体易位重排所产生的MLL1融合蛋白则与急性白血病的发生发展密切相关。目前人们对MLL1蛋白的结构和功能研究取得了很大的进展,为以MLL1和其相互作用蛋白为靶点的新型MLL白血病药物设计奠定了坚实的基础。

Histone H3K4 methyltransferase MLL1 has been intensively studied because of its involvement by chromosomal translocation in mixed lineage leukemia. MLL1 plays a pivotal role in gene regulation, development and differentiation. Chromosome translocations of MLL1 generate chimeric proteins containing MLL1 Nterminus fused in-frame with distinct partner proteins, which contribute to leukemogenesis. Recent progress hasbegun to reveal the structures and functions of MLL1 protein, which, in turn, have provided new opportunities for therapeutic development towards mixed lineage leukemia.