Pontin52 and Reptin52 function as antagonistic regulators of β-catenin signalling activity
Pontin52 and Reptin52 function as antagonistic regulators of β-catenin signalling activity
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DOI：
10.1093/emboj/19.22.6121
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发表时间：
2000-11-15
期刊：
影响因子：
11.4
通讯作者：
Pradel, J
中科院分区：
文献类型：
--
作者：
Bauer, A;Chauvet, S;Pradel, J
在Wnt刺激的细胞中，β-连环蛋白在细胞质中变得稳定，进入细胞核并与淋巴增强因子-I（LEF-1）/T细胞因子（TCF）家族的HMG盒转录因子相互作用，从而刺激特异性靶基因的转录。我们最近鉴定了Pontin 52作为与β-连环蛋白和TATA盒结合蛋白（TBP）相互作用的核蛋白，表明其参与调节β-连环蛋白介导的反式激活。在此，我们报告了Reptin 52作为Pontin 52的相互作用伴侣的鉴定，与Pontin 52高度同源，Reptin 52同样结合β-连环蛋白和TBP。使用报告基因测定，我们证明了这两种蛋白质拮抗地影响β-连环蛋白-TCF复合物的反式激活潜力。此外，我们证明了这种机制在果蝇中的进化保守性，dpontin和dreptin是体内无翼信号传导控制中拮抗作用的必需基因。这些结果表明，Pontin 52和Reptin 52对β-连环蛋白介导的反式激活的相反作用构成了控制经典Wingless/Wnt途径的额外机制。
In Wnt-stimulated cells, beta -catenin becomes stabilized in the cytoplasm, enters the nucleus and interacts with HMG box transcription factors of the lymphoid-enhancing factor-1 (LEF-1)/T-cell factor (TCF) family, thereby stimulating the transcription of specific target genes. We recently identified Pontin52 as a nuclear protein interacting with beta -catenin and the TATA-box binding protein (TBP), suggesting its involvement in regulating beta -catenin-mediated transactivation, Here, we report the identification of Reptin52 as an interacting partner of Pontin52, Highly homologous to Pontin52, Reptin52 likewise binds beta -catenin and TBP, Using reporter gene assays, we show that the two proteins antagonistically influence the transactivation potential of the beta -catenin-TCF complex, Furthermore, we demonstrate the evolutionary conservation of this mechanism in Drosophila, dpontin and dreptin are essential genes that act antagonistically in the control of Wingless signalling in vivo. These results indicate that the opposite action of Pontin52 and Reptin52 on beta -catenin-mediated transactivation constitutes an additional mechanism for the control of the canonical Wingless/Wnt pathway.