PUBLICATION

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

Authors
Brembeck, F.H., Schwarz-Romond, T., Bakkers, J., Wilhelm, S., Hammerschmidt, M., and Birchmeier, W.
ID
ZDB-PUB-040920-3
Date
2004
Source
Genes & Development   18(18): 2225-2230 (Journal)
Registered Authors
Bakkers, Jeroen, Hammerschmidt, Matthias
Keywords
BCL9/legless; beta-catenin; Wnt8; tyrosine phosphorylation; epithelial–mesenchymal transition; mesoderm patterning
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
  • RNA Interference
  • Sequence Homology, Amino Acid
  • Trans-Activators/genetics
  • Trans-Activators/metabolism*
  • Transcription, Genetic*
  • Tyrosine/metabolism
  • Wnt Proteins
  • Zebrafish/embryology
  • Zebrafish Proteins
  • beta Catenin
PubMed
15371335 Full text @ Genes & Dev.
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.
Genes / Markers
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Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
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Mapping