Essential role of BCL9-2 in the switch between beta-catenin's adhesive and transcriptional functions

Genes Dev. 2004 Sep 15;18(18):2225-30. doi: 10.1101/gad.317604. Epub 2004 Sep 1.

Abstract

beta-Catenin controls both cadherin-mediated cell adhesion and activation of Wnt target genes. We demonstrate here that the beta-catenin-binding protein BCL9-2, a homolog of the human proto-oncogene product BCL9, induces epithelial-mesenchymal transitions of nontransformed cells and increases beta-catenin-dependent transcription. RNA interference of BCL9-2 in carcinoma cells induces an epithelial phenotype and translocates beta-catenin from the nucleus to the cell membrane. The switch between beta-catenin's adhesive and transcriptional functions is modulated by phosphorylation of Tyr 142 of beta-catenin, which favors BCL9-2 binding and precludes interaction with alpha-catenin. During zebrafish embryogenesis, BCL9-2 acts in the Wnt8-signaling pathway and regulates mesoderm patterning.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Body Patterning
  • Carrier Proteins / physiology*
  • Cell Adhesion / physiology
  • Cell Line, Transformed
  • Cell Membrane / metabolism
  • Cell Movement
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Embryo, Nonmammalian
  • Epithelial Cells / physiology
  • Humans
  • Mesoderm / cytology
  • Mesoderm / physiology
  • Mice
  • Neoplasm Proteins / physiology*
  • Phosphorylation
  • Protein Transport / physiology
  • Proteins / metabolism
  • Proto-Oncogene Mas
  • RNA Interference
  • Sequence Homology, Amino Acid
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors
  • Transcription, Genetic*
  • Tyrosine / metabolism
  • Wnt Proteins
  • Zebrafish / embryology
  • Zebrafish Proteins
  • beta Catenin

Substances

  • BCL9 protein, human
  • CTNNB1 protein, human
  • CTNNB1 protein, mouse
  • Carrier Proteins
  • Cytoskeletal Proteins
  • MAS1 protein, human
  • Neoplasm Proteins
  • Proteins
  • Proto-Oncogene Mas
  • Trans-Activators
  • Transcription Factors
  • Wnt Proteins
  • Zebrafish Proteins
  • bcl9l protein, zebrafish
  • beta Catenin
  • ctnnb1 protein, zebrafish
  • wnt8a protein, zebrafish
  • Tyrosine