MOZ and MORF acetyltransferases: Molecular interaction, animal development and human disease.
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.
The Rosalind & Morris Goodman Cancer Research Center, McGill University, Montreal, Quebec H3A 1A3, Canada; Department of Medicine, McGill University, Montreal, Quebec H3A 1A3, Canada; Department of Biochemistry, McGill University, Montreal, Quebec H3A 1A3, Canada; McGill University Health Center, Montreal, Quebec H3A 1A3, Canada. Electronic address: xiang-jiao.yang@mcgill.ca.
Xiang-Jiao
XJ
Yang
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000328:Adult; D000818:Animals; D004268:DNA-Binding Proteins; D004194:Disease / Q000235:genetics*; D048788:Growth and Development / Q000235:genetics*; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D000092468:Bromodomain Containing Proteins
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D051548:Histone Acetyltransferases; D006657:Histones; D009687:Nuclear Proteins; C086011:BRPF1 protein, human; D000092468:Bromodomain Containing Proteins; C108712:KAT6A protein, human; C487137:KAT6B protein, human
BRPF1; BRPF2; BRPF3; HBO1; Histone acetyltransferase; ING5