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

Mech Dev. 1999 Mar;81(1-2):65-74. doi: 10.1016/s0925-4773(98)00225-1.

Abstract

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

MeSH terms

  • Animals
  • Blotting, Western
  • Cytoskeletal Proteins / chemistry
  • Cytoskeletal Proteins / physiology*
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation, Developmental
  • Genes, Reporter
  • Luciferases / metabolism
  • Lymphoid Enhancer-Binding Factor 1
  • Models, Genetic
  • Plasmids
  • Proto-Oncogene Proteins / metabolism
  • RNA / administration & dosage
  • Recombinant Fusion Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Time Factors
  • Trans-Activators*
  • Transcription Factors / metabolism*
  • Transcriptional Activation
  • Wnt Proteins
  • Xenopus Proteins
  • Xenopus laevis / embryology*
  • Zebrafish Proteins*
  • beta Catenin

Substances

  • CTNNB1 protein, Xenopus
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • Lymphoid Enhancer-Binding Factor 1
  • Proto-Oncogene Proteins
  • Recombinant Fusion Proteins
  • Trans-Activators
  • Transcription Factors
  • Wnt Proteins
  • Xenopus Proteins
  • Zebrafish Proteins
  • beta Catenin
  • RNA
  • Luciferases