The role of MOZ/KAT6A in hematological malignancies and advances in MOZ/KAT6A inhibitors. (December 2021)

• Record Type: Journal Article
• Authors: Su, Jingtian; Wang, Xuan; Bai, Yuwei; Sun, Moran; Yao, Yongfang; Duan, Yongtao
• Is Part Of: Pharmacological research. Volume 174(2021)
• Publication Date: 2021-12
• Subjects: MYST (MOZ, Ybf2/Sas3, Sas2, Tip60) -- MOZ/KAT6A monocytic leukemia zinc finger protein -- Ybf2/Sas3 something about silencing 3 -- Sas2 something about silencing 2 -- Tip60/KAT5 HIV-tat interacting protein 60 KD -- HATs histone acetyltransferases -- HSCs hematopoietic stem cells -- MOF/KAT8 males absent on the first -- HBO1/KAT7 histone acetyltransferase binding to ORC1 -- MORF/KAT6B MOZ related factor -- AML acute myeloid leukemia -- CBP CREB-binding protein -- p300 E1A-associated p300 kDa protein -- TIF2 nuclear receptor cofactor -- NCOA3 nuclear receptor coactivator 3 -- PU.1 Spi-1 proto-oncogene -- PHD plant homologous structural domain -- NEMM N-terminal part of Enok, MOZ or MORF -- SM serine/methionine enriched region -- P proline/glutamine stretch -- Acidic acidic region -- DPF The tandem PHD zinc finger -- CH cysteine/histidine-rich motif -- Chromo chromatin organization modifier domain -- Ser serine-rich domain. Br, bromodomain -- KIX phospho-CREB-interacting module -- bHLH basic helix–loop–helix -- PAS Per, aryl hydrocarbon receptor (AhR) and single-minded homology -- Q glutamine-rich domain -- NID nuclear receptor-interacting domain -- BN1 BRPF N-terminal conserved region 1 -- BN2 BRPF N-terminal conserved region 2 -- I the N-terminal halves of the Epc homology domain -- M the C-terminal halves of the Epc homology domain -- Zn monoknuckle zinc finger -- Bromo bromodomain -- PWWP (proline-tryptophan-tryptophan-proline)-containing structural domain -- ING ING N-terminal domain -- LZ leucine zipper -- ING5 growth inhibitory factor 5 -- hEAF6 homolog of ESA1-related factor 6 -- COO cells of origin -- MEFs mouse embryonic fibroblasts; CTx-0124143(PubChem CID:877350) -- WM-8014(PubChem CID: 133053564) -- WM-1119(PubChem CID: 133080719) -- WM-3835(PubChem CID:134581412) -- Compound-5(PubChem CID: 1079024); Hematological malignancies -- MOZ -- MYST -- MOZ inhibitor; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2021.105930
• Languages: English
• ISSNs: 1043-6618

Abstract

Abstract: 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. Graphical Abstract: ga1