E-cadherin binding prevents beta-catenin nuclear localization and beta-catenin/LEF-1-mediated transactivation

J Cell Sci. 1999 Apr;112 ( Pt 8):1237-45.

Abstract

Beta-catenin is a multifunctional protein found in three cell compartments: the plasma membrane, the cytoplasm and the nucleus. The cell has developed elaborate ways of regulating the level and localization of beta-catenin to assure its specific function in each compartment. One aspect of this regulation is inherent in the structural organization of beta-catenin itself; most of its protein-interacting motifs overlap so that interaction with one partner can block binding of another at the same time. Using recombinant proteins, we found that E-cadherin and lymphocyte-enhancer factor-1 (LEF-1) form mutually exclusive complexes with beta-catenin; the association of beta-catenin with LEF-1 was competed out by the E-cadherin cytoplasmic domain. Similarly, LEF-1 and adenomatous polyposis coli (APC) formed separate, mutually exclusive complexes with beta-catenin. In Wnt-1-transfected C57MG cells, free beta-catenin accumulated and was able to associate with LEF-1. The absence of E-cadherin in E-cadherin-/- embryonic stem (ES) cells also led to an accumulation of free beta-catenin and its association with LEF-1, thereby mimicking Wnt signaling. beta-catenin/LEF-1-mediated transactivation in these cells was antagonized by transient expression of wild-type E-cadherin, but not of E-cadherin lacking the beta-catenin binding site. The potent ability of E-cadherin to recruit beta-catenin to the cell membrane and prevent its nuclear localization and transactivation was also demonstrated using SW480 colon carcinoma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli Protein
  • Binding, Competitive
  • Blotting, Western
  • Cadherins / physiology*
  • Cell Membrane / metabolism
  • Cell Nucleus / metabolism*
  • Cells, Cultured
  • Cytoskeletal Proteins / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Kinetics
  • Lymphoid Enhancer-Binding Factor 1
  • Precipitin Tests
  • Protein Binding
  • Proto-Oncogene Proteins / metabolism
  • Recombinant Fusion Proteins
  • Signal Transduction
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Trans-Activators*
  • Transcription Factors / metabolism*
  • Transcriptional Activation*
  • Wnt Proteins
  • Wnt1 Protein
  • Zebrafish Proteins*
  • beta Catenin

Substances

  • Adenomatous Polyposis Coli Protein
  • CTNNB1 protein, human
  • Cadherins
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • LEF1 protein, human
  • Lymphoid Enhancer-Binding Factor 1
  • Proto-Oncogene Proteins
  • Recombinant Fusion Proteins
  • Trans-Activators
  • Transcription Factors
  • WNT1 protein, human
  • Wnt Proteins
  • Wnt1 Protein
  • Zebrafish Proteins
  • beta Catenin