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

beta-Catenin is a multifunctional protein involved in cell adhesion and com munication. In response to signaling by Wnt growth factors, beta-catenin as sociates with nuclear TCF factors to activate target genes. A transactivati on domain identified at the C-terminus of beta-catenin can stimulate expres sion of artificial reporter genes. However, the mechanism of target gene-ac tivation by TCF/beta-catenin complexes and the physiological relevance of t he beta-catenin transactivation domain still remain unclear. Here we asked whether the beta-catenin transactivation domain can generate a Wne-response in a complex biological system, namely axis formation during Xenopus laevi s embryogenesis. We show that a chimeric transcription factor consisting of beta-catenin fused to the DNA-binding domain of LEF-1 induces a complete s econdary dorsoanterior axis when expressed in Xenopus. A LEF-1-beta-catenin fusion lacking the C-terminal transactivation domain is impaired in signal ing while fusion of just the beta-catenin transactivator to the DNA-binding domain of LEF-1 is sufficient for axis-induction. The latter fusion molecu le is blocked by dominant negative LEF-1 but not by excess cadherin indicat ing that all events parallel or upstream of the transactivation step mediat ed by beta-catenin are dispensable for Wnt-signaling. Moreover, beta-cateni n can be replaced by a heterologous transactivator. Apparently, the ultimat e function of beta-catenin in Wnt signaling is to recruit the basal transcr iption machinery to promoter regions of specific target genes. (C) 1999 Els evier Science Ireland Ltd. All rights reserved.