MOZ-TIF2-induced acute myeloid leukemia requires the MOZ nucleosome binding motif and TIF2-mediated recruitment of CBP
MOZ-TIF2-induced acute myeloid leukemia requires the MOZ nucleosome binding motif and TIF2-mediated recruitment of CBP
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DOI：
10.1016/s1535-6108(03)00051-5
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发表时间：
2003-03-01
期刊：
影响因子：
50.3
通讯作者：
Gilliland, DG
中科院分区：
文献类型：
--
作者：
Deguchi, K;Ayton, PM;Gilliland, DG
MOZ-TIF 2融合与inv（8）（p11 q13）急性髓性白血病（AML）相关。MOZ是MYST家族组蛋白乙酰转移酶（HAT），而TIF 2是与CREB结合蛋白（CBP）相关的核受体辅激活剂。在这里，我们证明了MOZ-TIF 2在体外具有转化特性，并在小鼠骨髓移植试验中引起AML。MOZ的C2 HC核小体识别基序对于转化是必需的，而MOZ HAT活性是必需的。然而，MOZ-TIF 2通过TIF 2 CBP相互作用结构域（CID）与CBP相互作用对于转化是必需的。这些结果表明，MOZ的核小体靶向和TIF 2对CBP的募集是MOZ-TIF 2转化的关键要求，并表明MOZ功能的获得有助于白血病发生。
The MOZ-TIF2 fusion is associated with acute myeloid leukemia (AML) with inv(8)(p11q13). MOZ is a MYST family histone acetyltransferase (HAT), whereas TIF2 is a nuclear receptor coactivator that associates with CREB binding protein (CBP). Here we demonstrate that MOZ-TIF2 has transforming properties in vitro and causes AML in a murine bone marrow transplant assay. The C2HC nucleosome recognition motif of MOZ is essential for transformation, whereas MOZ HAT activity is dispensable. However, MOZ-TIF2 interaction with CBP through the TIF2 CBP interaction domain (CID) is essential for transformation. These results indicate that nucleosomal targeting by MOZ and recruitment of CBP by TIF2 are critical requirements for MOZ-TIF2 transformation and indicate that MOZ gain of function contributes to leukemogenesis.