Troke Philip J F, Kindle Karin B, Collins Hilary M, Heery David M
School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
Biochem Soc Symp. 2006(73):23-39. doi: 10.1042/bss0730023.
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.
MOZ（单核细胞白血病锌指蛋白；也称为ZNF220或MYST3）是蛋白质乙酰转移酶MYST家族的成员。涉及MOZ基因的染色体易位与急性髓系白血病（AML）相关，这表明它在造血过程中发挥作用。反复出现的相互易位将MOZ基因[或编码MORF（MOZ相关因子）的基因；也称为MYST4]与编码核受体共激活因子CBP[CREB（cAMP反应元件结合蛋白）结合蛋白]、p300或p160蛋白TIF2（转录中介因子2）的基因融合。产生的融合蛋白可在体外转化造血祖细胞，并在小鼠中诱发骨髓增殖性疾病。最近对这些效应背后分子机制的深入了解表明，MOZ融合蛋白会干扰核受体、p53和Runx蛋白等转录因子的活性。我们的研究表明，破坏细胞CBP和p300蛋白的功能可能在这一过程中起关键作用。在此，我们综述了在理解MOZ融合蛋白在AML病因学中作用方面的最新进展。
