MYND结构域识别SMRT/N-CoR的结构基础及其对AML1/ETO活性的作用。
Structural basis for recognition of SMRT/N-CoR by the MYND domain and its contribution to AML1/ETO's activity.
作者信息
Liu Yizhou, Chen Wei, Gaudet Justin, Cheney Matthew D, Roudaia Liya, Cierpicki Tomasz, Klet Rachel C, Hartman Kari, Laue Thomas M, Speck Nancy A, Bushweller John H
机构信息
Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22906, USA.
出版信息
Cancer Cell. 2007 Jun;11(6):483-97. doi: 10.1016/j.ccr.2007.04.010.
Abstract
AML1/ETO results from the t(8;21) associated with 12%-15% of acute myeloid leukemia. The AML1/ETO MYND domain mediates interactions with the corepressors SMRT and N-CoR and contributes to AML1/ETO's ability to repress proliferation and differentiation of primary bone marrow cells as well as to enhance their self renewal in vitro. We solved the solution structure of the MYND domain and show it to be structurally homologous to the PHD and RING finger families of proteins. We also determined the solution structure of an MYND-SMRT peptide complex. We demonstrated that a single amino acid substitution that disrupts the interaction between the MYND domain and the SMRT peptide attenuated AML1/ETO's effects on proliferation, differentiation, and gene expression.
摘要
AML1/ETO 由与 12% - 15%的急性髓系白血病相关的 t(8;21)产生。AML1/ETO 的 MYND 结构域介导与共抑制因子 SMRT 和 N-CoR 的相互作用，并有助于 AML1/ETO 抑制原代骨髓细胞增殖和分化以及增强其体外自我更新的能力。我们解析了 MYND 结构域的溶液结构，并表明它在结构上与蛋白质的 PHD 和环指家族同源。我们还确定了 MYND - SMRT 肽复合物的溶液结构。我们证明，破坏 MYND 结构域与 SMRT 肽之间相互作用的单个氨基酸取代减弱了 AML1/ETO 对增殖、分化和基因表达的影响。
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