Borrow J, Stanton V P, Andresen J M, Becher R, Behm F G, Chaganti R S, Civin C I, Disteche C, Dubé I, Frischauf A M, Horsman D, Mitelman F, Volinia S, Watmore A E, Housman D E
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139, USA.
Nat Genet. 1996 Sep;14(1):33-41. doi: 10.1038/ng0996-33.
The recurrent translocation t(8;16)(p11;p13) is a cytogenetic hallmark for the M4/M5 subtype of acute myeloid leukaemia. Here we identify the breakpoint-associated genes. Positional cloning on chromosome 16 implicates the CREB-binding protein (CBP), a transcriptional adaptor/coactivator protein. At the chromosome 8 breakpoint we identify a novel gene, MOZ, which encodes a 2,004-amino-acid protein characterized by two C4HC3 zinc fingers and a single C2HC zinc finger in conjunction with a putative acetyltransferase signature. In-frame MOZ-CBP fusion transcripts combine the MOZ finger motifs and putative acetyltransferase domain with a largely intact CBP. We suggest that MOZ may represent a chromatin-associated acetyltransferase, and raise the possibility that a dominant MOZ-CBP fusion protein could mediate leukaemogenesis via aberrant chromatin acetylation.
复发性易位t(8;16)(p11;p13)是急性髓系白血病M4/M5亚型的细胞遗传学特征。在此我们鉴定了与断点相关的基因。在16号染色体上进行的定位克隆表明涉及CREB结合蛋白（CBP），一种转录衔接子/共激活蛋白。在8号染色体断点处，我们鉴定出一个新基因MOZ，它编码一种含2004个氨基酸的蛋白质，其特征为两个C4HC3锌指和一个单一的C2HC锌指，以及一个假定的乙酰转移酶特征序列。读框内的MOZ-CBP融合转录本将MOZ的指状基序和假定的乙酰转移酶结构域与基本完整的CBP相结合。我们认为MOZ可能代表一种与染色质相关的乙酰转移酶，并提出一种显性的MOZ-CBP融合蛋白可能通过异常的染色质乙酰化介导白血病发生的可能性。
