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Hot spots in beta-catenin for interactions with LEF-1, conductin and APC.

Interactions between beta-catenin and LEF-1/TCF, APC and conductin/axin are essential for wnt-controlled stabilization of beta-catenin and transcriptional activation. The wnt signal transduction pathway is important in both embryonic development and tumor progression. We identify here amino acid residues in beta-catenin that distinctly affect its binding to LEF-1/TCF, APC and conductin. These residues form separate surface clusters, termed hot spots, along the armadillo superhelix of beta-catenin. We also show that complementary charged and hydrophobic amino acids are required for formation of the bipartite beta-catenin-LEF-1 transcription factor. Moreover, we demonstrate that conductin/axin binding to beta-catenin is essential for beta-catenin degradation, and that APC acts as a cofactor of conductin/axin in this process. Binding of APC to conductin/axin activates the latter and occurs between their SAMP and RGS domains, respectively.

Pubmed ID: 10966653

Authors

  • von Kries JP
  • Winbeck G
  • Asbrand C
  • Schwarz-Romond T
  • Sochnikova N
  • Dell'Oro A
  • Behrens J
  • Birchmeier W

Journal

Nature structural biology

Publication Data

September 28, 2000

Associated Grants

None

Mesh Terms

  • Adenomatous Polyposis Coli Protein
  • Amino Acid Sequence
  • Animals
  • Axin Protein
  • Binding Sites
  • Cell Line
  • Conserved Sequence
  • Crystallography, X-Ray
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • Dogs
  • Humans
  • Ligands
  • Lymphoid Enhancer-Binding Factor 1
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Neoplasm Proteins
  • Phosphorylation
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Trans-Activators
  • Transcription Factors
  • Transcriptional Activation
  • Transfection
  • Two-Hybrid System Techniques
  • beta Catenin