Modulation of transcriptional regulation by LEF-1 in response to Wnt-1 signaling and association with β-catenin
Modulation of transcriptional regulation by LEF-1 in response to Wnt-1 signaling and association with β-catenin
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DOI：
10.1128/mcb.18.8.4807
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发表时间：
1998-08-01
影响因子：
5.3
通讯作者：
Grosschedl, R
中科院分区：
文献类型：
--
作者：
Hsu, SC;Galceran, J;Grosschedl, R
Wnt信号被认为是通过β-连环蛋白与LEF - 1/TCF转录因子家族成员之间的相互作用来介导的。在此，我们研究了在NIH 3T3细胞内源性β-连环蛋白条件下，LEF - 1响应Wnt - 1信号进行转录调控的机制，并且我们检验了与β-连环蛋白的结合对于LEF - 1的功能是否是必需的。我们发现Wnt - 1信号通过在细胞核中与β-连环蛋白结合赋予LEF - 1转录激活潜能。通过诱变，我们确定了LEF - 1中对与β-连环蛋白相互作用重要的特定残基，并且我们描绘了β-连环蛋白中的两个转录激活结构域，其功能在与LEF - 1特异性结合时增强。最后，我们表明在T细胞受体α增强子的调控中，Wnt - 1信号和β-连环蛋白的结合对于LEF - 1的结构功能不是必需的，这涉及LEF - 1与一种不同的辅因子ALY的结合。因此，LEF - 1通过与不同蛋白质结合可以承担多种调节功能。
Wnt signaling is thought to be mediated via interactions between beta-catenin and members of the LEF-1/TCF family of transcription factors. Here we study the mechanism of transcriptional regulation by LEF-1 in response to a Wnt-1 signal under conditions of endogenous beta-catenin in NIH 3T3 cells, and we examine whether association with beta-catenin is obligatory for the function of LEF-1. We find that Wnt-1 signaling confers transcriptional activation potential upon LEF-1 by association with beta-catenin in the nucleus. By mutagenesis, we identified specific residues in LEF-1 important for interaction with beta-catenin, and we delineated two transcriptional activation domains in beta-catenin whose function is augmented in specific association with LEF-1. Finally, we show that a Wnt-1 signal and beta-catenin association are not required for the architectural function of LEF-1 in the regulation of the T-cell receptor alpha enhancer, which involves association of LEF-1 with a different cofactor, ALY. Thus, LEF-1 can assume diverse regulatory functions by association with different proteins.