Hot spots in beta-catenin for interactions with LEF-1, conductin and APC.
Nat Struct Biol
; 7(9): 800-7, 2000 Sep.
Article
en En
| MEDLINE
| ID: mdl-10966653
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.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Transactivadores
/
Proteínas del Citoesqueleto
/
Proteínas de Unión al ADN
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Nat Struct Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2000
Tipo del documento:
Article
País de afiliación:
Alemania