MOZ fusion proteins in acute myeloid leukaemia.
MOZ (monocytic leukaemia zinc finger protein; also known as ZNF220 or MYST3) is a member of the MYST family of protein acetyltransferases. Chromosomal translocations involving the MOZ gene are associated with AML (acute myeloid leukaemia), suggesting that it has a role in haematopoiesis. Recurrent reciprocal translocations fuse the MOZ gene [or the gene encoding MORF (MOZ-related factor); also known as MYST4] to genes encoding the nuclear receptor co-activators CBP [CREB (cAMP response element-binding protein)-binding protein], p300 or the p160 protein TIF2 (transcription intermediary factor 2). The resulting fusion proteins can transform haematopoietic progenitors in vitro, and induce myeloproliferative disease in mice. Recent insights into the molecular mechanisms underlying these effects indicate that MOZ fusion proteins interfere with the activities of transcription factors such as nuclear receptors, p53 and Runx proteins. Our studies suggest that subverting the function of cellular CBP and p300 proteins may play a key role in this process. Here we review the recent progress in understanding the role of MOZ fusion proteins in the aetiology of AML.
Troke
Philip J F
PJ
School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
Kindle
Karin B
KB
Collins
Hilary M
HM
Heery
David M
DM
D000818:Animals; D050882:CREB-Binding Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D050939:Gene Fusion; D051548:Histone Acetyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D051958:Nuclear Receptor Coactivator 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D016335:Zinc Fingers / Q000235:genetics
C498001:NCOA2 protein, human; D051958:Nuclear Receptor Coactivator 2; D015514:Oncogene Proteins, Fusion; D015534:Trans-Activators; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D051548:Histone Acetyltransferases; C108712:KAT6A protein, human