Hot spots in beta-catenin for interactions with LEF-1, conductin and APC.
2000
Interactions between -catenin and LEF-1/TCF, APC and conductin/axin are essential for wnt-controlled stabilization of -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 -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 -catenin. We also show that complementary charged and hydrophobic amino acids are required for formation of the bipartite -catenin−LEF-1 transcription factor. Moreover, we demonstrate that conductin/axin binding to -catenin is essential for -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.
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