Critical scaffolding regions of the tumor suppressor Axin1 are natively unfolded.
J Mol Biol
; 405(3): 773-86, 2011 Jan 21.
Article
en En
| MEDLINE
| ID: mdl-21087614
ABSTRACT
The Wnt pathway tumor-suppressor protein Axin coordinates the formation of a critical multiprotein destruction complex that serves to downregulate ß-catenin protein levels, thereby preventing target gene activation. Given the lack of structural information on some of the major functional parts of Axin, it remains unresolved how the recruitment and positioning of Wnt pathway kinases, such as glycogen synthase kinase 3ß, are coordinated to bring about ß-catenin phosphorylation. Using various biochemical and biophysical methods, we demonstrate here that the central region of Axin that is implicated in binding glycogen synthase kinase 3ß and ß-catenin is natively unfolded. Our results support a model in which the unfolded nature of these critical scaffolding regions in Axin facilitates dynamic interactions with a kinase and its substrate, which in turn act upon each other.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Represoras
/
Proteínas Supresoras de Tumor
/
Regiones de Fijación a la Matriz
/
Proteínas Adaptadoras Transductoras de Señales
/
Desplegamiento Proteico
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Mol Biol
Año:
2011
Tipo del documento:
Article
País de afiliación:
Países Bajos