The C-terminal transactivation domain of β-catenin is necessary and sufficient for signaling by the LEF-1/β-catenin complex in Xenopus laevis

Abstract

β-Catenin is a multifunctional protein involved in cell adhesion and communication. In response to signaling by Wnt growth factors, β-catenin associates with nuclear TCF factors to activate target genes. A transactivation domain identified at the C-terminus of β-catenin can stimulate expression of artificial reporter genes. However, the mechanism of target gene activation by TCF/β-catenin complexes and the physiological relevance of the β-catenin transactivation domain still remain unclear. Here we asked whether the β-catenin transactivation domain can generate a Wnt-response in a complex biological system, namely axis formation during Xenopus laevis embryogenesis. We show that a chimeric transcription factor consisting of β-catenin fused to the DNA-binding domain of LEF-1 induces a complete secondary dorsoanterior axis when expressed in Xenopus. A LEF-1-β-catenin fusion lacking the C-terminal transactivation domain is impaired in signaling while fusion of just the β-catenin transactivator to the DNA-binding domain of LEF-1 is sufficient for axis-induction. The latter fusion molecule is blocked by dominant negative LEF-1 but not by excess cadherin indicating that all events parallel or upstream of the transactivation step mediated by β-catenin are dispensable for Wnt-signaling. Moreover, β-catenin can be replaced by a heterologous transactivator. Apparently, the ultimate function of β-catenin in Wnt signaling is to recruit the basal transcription machinery to promoter regions of specific target genes.