MOZ and MORF acetyltransferases: Molecular interaction, animal development and human disease

• Published in: Biochimica et biophysica acta Vol. 1853; no. 8; pp. 1818 - 1826
• Main Author: Yang, Xiang-Jiao
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2015
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Adult; Animals; BRPF1; BRPF2; BRPF3; Disease - genetics; Growth and Development - genetics; HBO1; Histone acetyltransferase; Histone Acetyltransferases - metabolism; Histones - metabolism; Humans; ING5; Nuclear Proteins - metabolism; Protein Binding; ING5; BRPF1; BRPF2; BRPF3; Histone acetyltransferase; HBO1
• ISSN: 0167-4889; 0006-3002; 1879-2596
• DOI: 10.1016/j.bbamcr.2015.04.014

Lysine residues are subject to many forms of covalent modification and one such modification is acetylation of the ε-amino group. Initially identified on histone proteins in the 1960s, lysine acetylation is now considered as an important form of post-translational modification that rivals phosphorylation. However, only about a dozen of human lysine acetyltransferases have been identified. Among them are MOZ (monocytic leukemia zinc finger protein; a.k.a. MYST3 and KAT6A) and its paralog MORF (a.k.a. MYST4 and KAT6B). Although there is a distantly related protein in Drosophila and sea urchin, these two enzymes are vertebrate-specific. They form tetrameric complexes with BRPF1 (bromodomain- and PHD finger-containing protein 1) and two small non-catalytic subunits. These two acetyltransferases and BRPF1 play key roles in various developmental processes; for example, they are important for development of hematopoietic and neural stem cells. The human KAT6A and KAT6B genes are recurrently mutated in leukemia, non-hematologic malignancies, and multiple developmental disorders displaying intellectual disability and various other abnormalities. In addition, the BRPF1 gene is mutated in childhood leukemia and adult medulloblastoma. Therefore, these two acetyltransferases and their partner BRPF1 are important in animal development and human disease. •MOZ and MORF are transcriptional coactivators with acetyltransferase activity.•MOZ and MORF form tetrameric complexes with BRPF1 and two other subunits.•Each tetrameric complex possesses 5 PHD fingers, a bromodomain and one PWWP domain.•The MOZ and MORF genes are mutated in cancer and developmental disorders.•BRPF1 and its paralogs are important in animal development and human cancer.