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

b-Catenin is a multifunctional protein involved in cell adhesion and communication. In response to signaling by Wnt growth factors, bcatenin associates with nuclear TCF factors to activate target genes. A transactivation domain identified at the C-terminus of b-catenin can stimulate expression of artificial reporter genes. However, the mechanism of target gene activation by TCF/b-catenin complexes and the physiological relevance of the b-catenin transactivation domain still remain unclear. Here we asked whether the b-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 b-catenin fused to the DNA-binding domain of LEF-1 induces a complete secondary dorsoanterior axis when expressed in Xenopus. A LEF-1-b-catenin fusion lacking the C-terminal transactivation domain is impaired in signaling while fusion of just the b-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 b-catenin are dispensable for Wnt-signaling. Moreover, b-catenin can be replaced by a heterologous transactivator. Apparently, the ultimate function of b-catenin in Wnt signaling is to recruit the basal transcription machinery to promoter regions of specific target genes.  1999 Elsevier Science Ireland Ltd. All rights reserved.