Crystal structure of a beta-catenin/BCL9/Tcf4 complex.

Article Details

Citation

Sampietro J, Dahlberg CL, Cho US, Hinds TR, Kimelman D, Xu W

Crystal structure of a beta-catenin/BCL9/Tcf4 complex.

Mol Cell. 2006 Oct 20;24(2):293-300.

PubMed ID
17052462 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Catenin beta-1P35222Details