Cadherins mediate both the association between PS1 and beta-catenin and the effects of PS1 on beta-catenin stability.
J Biol Chem
; 280(43): 36007-12, 2005 Oct 28.
Article
en En
| MEDLINE
| ID: mdl-16126725
ABSTRACT
Presenilin1 (PS1), a protein involved in cellular development, forms functional complexes with beta-catenin, a regulator of Wnt signaling and cell-cell adhesion. In addition, both proteins have been shown to play important roles in disease including cancer and Alzheimer disease. Although PS1 and beta-catenin are found in the same complexes, it is not clear whether they bind directly to each other or a third complex component, like cadherin, may mediate their interactions. Here we show that PS1 and beta-catenin form no detectable complexes in cells that express no cadherin. In contrast, these complexes are readily found in E-cadherin containing cells. Furthermore, binding of both PS1 and beta-catenin to E-cadherin is necessary for the formation of PS1/beta-catenin complexes. Importantly, our data show that binding of PS1 to cadherin mediates the effects of PS1 on the phosphorylation, ubiquitination, and destabilization of beta-catenin. Thus, cadherins mediate both the association of PS1 and beta-catenin and the effects of PS1 on the cellular levels of beta-catenin.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cadherinas
/
Beta Catenina
/
Proteínas de la Membrana
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2005
Tipo del documento:
Article
País de afiliación:
Estados Unidos