Smad3 prevents beta-catenin degradation and facilitates beta-catenin nuclear translocation in chondrocytes.
J Biol Chem
; 285(12): 8703-10, 2010 Mar 19.
Article
em En
| MEDLINE
| ID: mdl-20097766
ABSTRACT
Our previous study demonstrated that transforming growth factor (TGF)-beta activates beta-catenin signaling through Smad3 interaction with beta-catenin in chondrocytes. In the present studies, we further investigated the detailed molecular mechanism of the cross-talk between TGF-beta/Smad3 and Wnt/beta-catenin signaling pathways. We found that C-terminal Smad3 interacted with both the N-terminal region and the middle region of beta-catenin protein in a TGF-beta-dependent manner. Both Smad3 and Smad4 were required for the interaction with beta-catenin and protected beta-catenin from an ubiquitin-proteasome-dependent degradation. In addition, the formation of the Smad3-Smad4-beta-catenin protein complex also mediated beta-catenin nuclear translocation. This Smad3-mediated regulatory mechanism of beta-catenin protein stability enhanced the activity of beta-catenin to activate downstream target genes during chondrogenesis. Our findings demonstrate a novel mechanism between TGF-beta and Wnt/beta-catenin signaling pathways during chondrocyte development.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Condrócitos
/
Transporte Ativo do Núcleo Celular
/
Proteína Smad3
/
Beta Catenina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos