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- Title
Hot spots in beta-catenin for interactions with LEF-1, conductin and APC.
- Authors
von Kries, J P; Winbeck, G; Asbrand, C; Schwarz-Romond, T; Sochnikova, N; Dell'Oro, A; Behrens, J; Birchmeier, W
- Abstract
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.
- Publication
Nature structural biology, 2000, Vol 7, Issue 9, p800
- ISSN
1072-8368
- Publication type
Journal Article
- DOI
10.1038/79039