Myb-binding protein 1a augments AhR-dependent gene expression
Myb-binding protein 1a augments AhR-dependent gene expression
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DOI：
10.1074/jbc.m200740200
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发表时间：
2002-06-21
影响因子：
4.8
通讯作者：
Whitlock, JP
中科院分区：
文献类型：
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作者：
Jones, LC;Okino, ST;Whitlock, JP
我们研究了芳香烃受体 (AhR) 的酸性结构域（氨基酸 515-583）反式激活靶基因的机制。谷胱甘肽 S-转移酶融合蛋白的研究表明，野生型酸性结构域在体外与 Myb 结合蛋白 1a 结合，而突变结构域（F542A、1569A）则不然。用含有野生型酸性结构域的 AhR 重建的 AhR 缺陷细胞表现出正常的 AhR 功能；然而，用含有突变酸性结构域的 AhR 重建的细胞不能正常工作。 Myb结合蛋白1a瞬时转染小鼠肝癌细胞与AhR依赖性基因表达的增强相关。当Myb结合蛋白1a转染到AhR缺陷型细胞中时，不会发生这种增强，而这些细胞是用缺乏酸性结构域的AhR重建的。我们推断1)Myb结合蛋白1a与AhR结合，从而增强反式激活，2)AhR酸性结构域的存在对于Myb结合蛋白1a增加AhR依赖性基因表达来说是必要且充分的。
We have studied the mechanism by which an acidic domain (amino acids 515-583) of the aromatic hydrocarbon receptor (AhR) transactivates a target gene. Studies with glutathione S-transferase fusion proteins demonstrate that the wild-type acidic domain associates in vitro with Myb-binding protein la, whereas a mutant domain (F542A, 1569A) does not. AhR-defective cells reconstituted with an AhR containing the wild-type acidic domain exhibit normal AhR function; however, cells reconstituted with an AhR containing the mutant acidic domain do not function normally. Transient transfection of Myb-binding protein la into mouse hepatoma cells is associated with augmentation of AhR-dependent gene expression. Such augmentation does not occur when Myb-binding protein la is transfected into AhR-defective cells that have been reconstituted with an AhR that lacks the acidic domain. We infer that 1) Myb-binding protein la associates with AhR, thereby enhancing transactivation, and 2) the presence of AhR's acidic domain is both necessary and sufficient for Myb-binding protein la to increase AhR-dependent gene expression.