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.
Mesh Terms:
Adenomatous Polyposis Coli Protein, Amino Acid Sequence, Animals, 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
Nat. Struct. Biol.
Date: Sep. 01, 2000
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