MOZ-TIF2诱导的急性髓系白血病需要MOZ核小体结合基序以及TIF2介导的CBP募集。
MOZ-TIF2-induced acute myeloid leukemia requires the MOZ nucleosome binding motif and TIF2-mediated recruitment of CBP.
作者信息
Deguchi Kenji, Ayton Paul M, Carapeti Melina, Kutok Jeffery L, Snyder Cynthia S, Williams Ifor R, Cross Nicholas C P, Glass Christopher K, Cleary Michael L, Gilliland D Gary
机构信息
Division of Hematology and Oncology, Brigham and Women's Hospital and Harvard Medical School, Harvard Institutes, of Medicine, 4 Blackfan Circle, Room 420, Boston, MA 02115, USA.
出版信息
Cancer Cell. 2003 Mar;3(3):259-71. doi: 10.1016/s1535-6108(03)00051-5.
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.
MOZ-TIF2融合与伴有inv(8)(p11q13)的急性髓系白血病（AML）相关。MOZ是一种MYST家族组蛋白乙酰转移酶（HAT），而TIF2是一种核受体辅激活因子，可与CREB结合蛋白（CBP）结合。在此，我们证明MOZ-TIF2在体外具有转化特性，并在小鼠骨髓移植试验中引发AML。MOZ的C2HC核小体识别基序对于转化至关重要，而MOZ的HAT活性则并非必需。然而，MOZ-TIF2通过TIF2的CBP相互作用结构域（CID）与CBP的相互作用对于转化至关重要。这些结果表明，MOZ对核小体的靶向作用以及TIF2对CBP的募集是MOZ-TIF2转化的关键要求，并表明MOZ功能获得有助于白血病发生。
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