Apoptosis induction and growth suppression by U19/Eaf2 is mediated through its ELL-binding domain
Apoptosis induction and growth suppression by U19/Eaf2 is mediated through its ELL-binding domain
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DOI：
10.1002/pros.20481
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发表时间：
2007-02-01
期刊：
影响因子：
2.8
通讯作者：
Wang, Zhou
中科院分区：
文献类型：
--
作者：
Hahn, Junghyun;Xiao, Wuhan;Wang, Zhou
背景。 U19/Eaf2 是一种雄激素反应基因，其下调在晚期人类前列腺癌中经常观察到。 U19/Eaf2 与 ELL 相互作用，ELL 是急性髓细胞性白血病 (11;19) (q23;p13.1) 易位中 MLL 的融合伴侣。 U19/ Eaf2 过表达诱导细胞凋亡并抑制异种移植肿瘤生长。使用转染和集落形成来测定各种U19/Eaf2突变体的细胞凋亡和生长抑制。进行免疫共沉淀以测试 U19/Eaf2 构建体与 ELL.RESULTS 之间的相互作用。 U19/Eaf2 对于细胞凋亡和生长抑制至关重要的区域被定位到氨基酸 68-113。该区域对于结合 ELL 是必要且充分的。 U19/Eaf2 和 ELL 在 293 细胞中的共表达导致细胞死亡和生长抑制显着增加。结论。这些观察结果表明，与 ELL 的相互作用对于 U19/Eaf2 诱导细胞凋亡和抑制生长至关重要。 (c) 2006 Wiley-Liss, Inc.
BACKGROUND. U19/Eaf2 is an androgen-response gene and its downregulation is frequently observed in advanced human prostate cancer. U19/Eaf2 interacts with ELL, a fusion partner of MLL in the (11;19) (q23;p13.1) translocation in acute mycloid leukemia. U19/ Eaf2 overexpression induces apoptosis and suppresses xenograft tumor growth.METHODS. Transfection and colony formation were used to assay for apoptosis and growth suppression of various U19/Eaf2 mutants. Co-immunoprecipitation was performed to test the interaction between the U19/Eaf2 constructs and ELL.RESULTS. The region of U19/Eaf2 essential for apoptosis and growth suppression was mapped to amino acids 68-113. This region was necessary and sufficient for binding ELL. Co-expression of U19/Eaf2 and ELL in 293 cells lead to significant increase in cell death and growth suppression.CONCLUSIONS. These observations argue that the interaction with ELL is essential for the induction of apoptosis and growth suppression by U19/Eaf2. (c) 2006 Wiley-Liss, Inc.