Nature structural biology, 2000-09, Vol.7 (9), p.800-807
2000
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- Autor(en) / Beteiligte
- Titel
- Hot spots in β-catenin for interactions with LEF-1, conductin and APC
- Ist Teil von
- Nature structural biology, 2000-09, Vol.7 (9), p.800-807
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2000
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1072-8368eISSN: 2331-365XDOI: 10.1038/79039Titel-ID: cdi_proquest_miscellaneous_72221010
- Format
- –
- Schlagworte
- Adenomatous Polyposis Coli Protein, Amino Acid Sequence, Animals, APC gene, Axin Protein, b-catenin, beta Catenin, Binding Sites, Cell Line, conductin, Conserved Sequence, Crystallography, X-Ray, Cytoskeletal Proteins - chemistry, Cytoskeletal Proteins - genetics, Cytoskeletal Proteins - metabolism, Cytoskeletal Proteins - pharmacology, DNA-Binding Proteins - chemistry, DNA-Binding Proteins - genetics, DNA-Binding Proteins - metabolism, Dogs, Humans, LEF-1 protein, Ligands, Lymphoid Enhancer-Binding Factor 1, Models, Molecular, Molecular Sequence Data, Mutation - genetics, Neoplasm Proteins - metabolism, Neoplasm Proteins - pharmacology, Phosphorylation - drug effects, Protein Binding, Protein Structure, Secondary, Protein Structure, Tertiary, Trans-Activators, Transcription Factors - chemistry, Transcription Factors - genetics, Transcription Factors - metabolism, Transcriptional Activation, Transfection, Two-Hybrid System Techniques