ENL, the MLL fusion partner in t(11;19), binds to the c-Abl interactor protein 1 (ABI1) that is fused to MLL in t(10;11)+
ENL, the MLL fusion partner in t(11;19), binds to the c-Abl interactor protein 1 (ABI1) that is fused to MLL in t(10;11)+
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DOI：
10.1038/sj.onc.1203506
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发表时间：
2000-03-30
期刊：
影响因子：
8
通讯作者：
Slany, RK
中科院分区：
文献类型：
--
作者：
Garcia-Cuéllar, MP;Schreiner, SA;Slany, RK
染色体位点11 q23的易位破坏MLL基因（或者ALL-I或HRX）经常在儿童白血病中发现。这些事件将MLL氨基末端与各种不相关的蛋白质在框内融合，迄今为止，已经表征了16种不同的融合伴侣，并且可能存在更多。在这些蛋白质中还没有检测到一般的统一特性。我们在这里表明，频繁的MLL融合伙伴ENL在19p13.1与人类同源的小鼠β-Interactor 1（ABI 1）蛋白相互作用。ABI 1又在t（10：11）（p11.2;q23）易位中与MLL融合，ABI 1通过酵母双杂交筛选被鉴定为ENL结合蛋白。ENL和ABI 1的相互作用可以在体外通过远蛋白质印迹分析和GST-下拉研究以及在体内通过免疫共沉淀实验来验证。结构-功能分析确定了ENL的内部区域和ABI 1的复合基序（包括SH 3结构域）作为相互结合伴侣。这些数据介绍了新的方面，可能有助于理解白血病的过程中MLL融合蛋白。
Translocations of the chromosomal locus 11q23 that disrupt the MLL gene (alternatively ALL-I or HRX) are frequently found in children's leukemias. These events fuse the MLL amino terminus in frame with a variety of unrelated proteins, Up to date, 16 different fusion partners have been characterized and more are likely to exist. No general unifying property could yet be detected amongst these proteins. We show here that the frequent MLL fusion partner ENL at 19p13.1 interacts with the human homologue of the mouse Abl-Interactor 1 (ABI1) protein. ABI1 in turn, is fused to MLL in the t(10:ll)(p11.2;q23) translocation, ABI1 was identified as an ENL binding protein by a yeast two-hybrid screen. The interaction of ENL and ABI1 could be verified in vitro by far-Western blot assays and GST-pulldown studies as well as in vivo by co-immunoprecipitation experiments. A structure-function analysis identified an internal region of ENL and a composite motif of ABI1 including an SH3 domain as mutual binding partners. These data introduce novel aspects that might contribute to the understanding of the process of leukemogenesis by MLL fusion proteins.