Henan Provincial Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou University, Zhengzhou 450018, China; School of Pharmaceutical Sciences, and Institute of Drug Discovery & Development, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, China.
Beijing Normal University, Beijing 100875, China.
Pharmacol Res. 2021 Dec;174:105930. doi: 10.1016/j.phrs.2021.105930. Epub 2021 Oct 6.
Hematological malignancies, unlike solid tumors, are a group of malignancies caused by abnormal differentiation of hematopoietic stem cells. Monocytic leukemia zinc finger protein (MOZ), a member of the MYST (MOZ, Ybf2/Sas3, Sas2, Tip60) family, is a histone acetyltransferase. MOZ is involved in various cellular functions: generation and maintenance of hematopoietic stem cells, development of erythroid cells, B-lineage progenitors and myeloid cells, and regulation of cellular senescence. Studies have shown that MOZ is susceptible to translocation in chromosomal rearrangements to form fusion genes, leading to the fusion of MOZ with other cellular regulators to form MOZ fusion proteins. Different MOZ fusion proteins have different roles, such as in the development and progression of hematological malignancies and inhibition of cellular senescence. Thus, MOZ is an attractive target, and targeting MOZ to design small-molecule drugs can help to treat hematological malignancies. This review summarizes recent progress in biology and medicinal chemistry for the histone acetyltransferase MOZ. In the biology section, MOZ and cofactors, structures of MOZ and related HATs, MOZ and fusion proteins, and roles of MOZ in cancer are discussed. In medicinal chemistry, recent developments in MOZ inhibitors are summarized.
血液系统恶性肿瘤与实体瘤不同，是一组由造血干细胞异常分化引起的恶性肿瘤。单核细胞白血病锌指蛋白（MOZ）是 MYST（MOZ、Ybf2/Sas3、Sas2、Tip60）家族的成员，是一种组蛋白乙酰转移酶。MOZ 参与多种细胞功能：造血干细胞的产生和维持、红细胞、B 谱系祖细胞和髓系细胞的发育以及细胞衰老的调节。研究表明，MOZ 易发生染色体重排中的易位，形成融合基因，导致 MOZ 与其他细胞调节剂融合形成 MOZ 融合蛋白。不同的 MOZ 融合蛋白具有不同的作用，例如在血液系统恶性肿瘤的发生和进展以及抑制细胞衰老中。因此，MOZ 是一个有吸引力的靶点，靶向 MOZ 设计小分子药物有助于治疗血液系统恶性肿瘤。本综述总结了组蛋白乙酰转移酶 MOZ 的生物学和药物化学的最新进展。在生物学部分，讨论了 MOZ 和辅助因子、MOZ 和相关 HAT 的结构、MOZ 和融合蛋白以及 MOZ 在癌症中的作用。在药物化学部分，总结了 MOZ 抑制剂的最新进展。
