Crystal structure of a beta-catenin/BCL9/Tcf4 complex.
Mol Cell
; 24(2): 293-300, 2006 Oct 20.
Article
em En
| MEDLINE
| ID: mdl-17052462
ABSTRACT
The canonical Wnt pathway plays critical roles in embryonic development, stem cell growth, and tumorigenesis. Stimulation of the Wnt pathway leads to the association of beta-catenin with Tcf and BCL9 in the nucleus, resulting in the transactivation of Wnt target genes. We have determined the crystal structure of a beta-catenin/BCL9/Tcf-4 triple complex at 2.6 A resolution. Our studies reveal that the beta-catenin binding site of BCL9 is distinct from that of most other beta-catenin partners and forms a good target for developing drugs that block canonical Wnt/beta-catenin signaling. The BCL9 beta-catenin binding domain (CBD) forms an alpha helix that binds to the first armadillo repeat of beta-catenin, which can be mutated to prevent beta-catenin binding to BCL9 without affecting cadherin or alpha-catenin binding. We also demonstrate that beta-catenin Y142 phosphorylation, which has been proposed to regulate BCL9-2 binding, does not directly affect the interaction of beta-catenin with either BCL9 or BCL9-2.
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Base de dados:
MEDLINE
Assunto principal:
Beta Catenina
/
Fatores de Transcrição TCF
/
Proteínas de Neoplasias
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article