Functional characterization of multiple transactivating elements in β-catenin, some of which interact with the TATA-binding protein in vitro
Functional characterization of multiple transactivating elements in β-catenin, some of which interact with the TATA-binding protein in vitro
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DOI：
10.1074/jbc.274.25.18017
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发表时间：
1999-06-18
影响因子：
4.8
通讯作者：
Kemler, R
中科院分区：
文献类型：
--
作者：
Hecht, A;Litterst, CM;Kemler, R
β -连环蛋白是犰狳重复蛋白家族的成员，在钙黏蛋白介导的细胞黏附和Wnt生长因子的信号传导中发挥双重作用。在Wnt刺激下，β -连环蛋白发生核转位，并作为T细胞因子DNA结合蛋白的转录共激活因子。此前已经证实了β -连环蛋白不同部分的反式激活潜能，但反式激活元件的确切位置尚未确定。此外，对于β -连环蛋白反式激活的机制以及β -连环蛋白与密切相关的犰狳蛋白和斑珠蛋白之间功能差异的分子基础了解甚少。在此，我们利用一个酵母系统对β -连环蛋白的反式激活特性进行了详细的表征。我们表明其反式激活结构域具有模块化结构，由多个亚元件组成，这些亚元件覆盖其N端和C端的广泛区域，并在很大程度上延伸到犰狳重复区域。与β -连环蛋白相比，斑珠蛋白和犰狳蛋白的N端具有不同的反式激活能力，这可能解释了它们不同的信号传导特性。此外，β -连环蛋白的反式激活元件在体外与TATA结合蛋白特异性且直接相互作用，这进一步证明了在Wnt信号传导过程中β -连环蛋白的一个主要功能是将基础转录机器招募到Wnt靶基因的启动子区域。
beta-Catenin, a member of the family of Armadillo repeat proteins, plays a dual role in cadherin-mediated cell adhesion and in signaling by Wnt growth factors, Upon Wnt stimulation beta-catenin undergoes nuclear translocation and serves as transcriptional coactivator of T cell factor DNA-binding proteins. Previously the transactivation potential of different portions of beta-catenin has been demonstrated, but the precise location of transactivating elements has not been established. Also, the mechanism of transactivation by beta-catenin and the molecular basis for functional differences between beta-catenin and the closely related proteins Armadillo and Plakoglobin are poorly understood. Here we have used a yeast system for the detailed characterization of the transactivation properties of beta-catenin. We show that its transactivation domains possess a modular structure, consist of multiple subelements that cover broad regions at its N and C termini, and extend considerably into the Armadillo repeat region. Compared with beta-catenin the N termini of Plakoglobin and Armadillo have different transactivation capacities that may explain their distinct signaling properties. Furthermore, transactivating elements of beta-catenin interact specifically and directly with the TATA-binding protein in vitro providing further evidence that a major function of beta-catenin during Wnt signaling is to recruit the basal transcription machinery to promoter regions of Wnt target genes.