Kitabayashi I, Aikawa Y, Nguyen L A, Yokoyama A, Ohki M
Cancer Genomics Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
EMBO J. 2001 Dec 17;20(24):7184-96. doi: 10.1093/emboj/20.24.7184.
The AML1-CBF beta transcription factor complex is the most frequent target of specific chromosome translocations in human leukemia. The MOZ gene, which encodes a histone acetyltransferase (HAT), is also involved in some leukemia-associated translocations. We report here that MOZ is part of the AML1 complex and strongly stimulates AML1-mediated transcription. The stimulation of AML1-mediated transcription is independent of the inherent HAT activity of MOZ. Rather, a potent transactivation domain within MOZ appears to be essential for stimulation of AML1-mediated transcription. MOZ, as well as CBP and MOZ-CBP, can acetylate AML1 in vitro. The amount of AML1-MOZ complex increases during the differentiation of M1 myeloid cells into monocytes/macrophages, suggesting that the AML1-MOZ complex might play a role in cell differentiation. On the other hand, the MOZ-CBP fusion protein, which is created by the t(8;16) translocation associated with acute monocytic leukemia, inhibits AML1-mediated transcription and differentiation of M1 cells. These results suggest that MOZ-CBP might induce leukemia by antagonizing the function of the AML1 complex.
AML1-CBFβ转录因子复合物是人类白血病中特定染色体易位最常见的靶点。编码组蛋白乙酰转移酶（HAT）的MOZ基因也参与了一些与白血病相关的易位。我们在此报告，MOZ是AML1复合物的一部分，并强烈刺激AML1介导的转录。AML1介导的转录刺激与MOZ固有的HAT活性无关。相反，MOZ内一个有效的反式激活结构域似乎对刺激AML1介导的转录至关重要。MOZ以及CBP和MOZ-CBP在体外均可使AML1乙酰化。在M1髓样细胞分化为单核细胞/巨噬细胞的过程中，AML1-MOZ复合物的量增加，这表明AML1-MOZ复合物可能在细胞分化中起作用。另一方面，由与急性单核细胞白血病相关的t(8;16)易位产生的MOZ-CBP融合蛋白抑制AML1介导的转录和M1细胞的分化。这些结果表明，MOZ-CBP可能通过拮抗AML1复合物的功能而诱发白血病。
