| First Author | Sampietro J | Year | 2006 |
| Journal | Mol Cell | Volume | 24 |
| Issue | 2 | Pages | 293-300 |
| PubMed ID | 17052462 | Mgi Jnum | J:306577 |
| Mgi Id | MGI:6716951 | Doi | 10.1016/j.molcel.2006.09.001 |
| Citation | Sampietro J, et al. (2006) Crystal structure of a beta-catenin/BCL9/Tcf4 complex. Mol Cell 24(2):293-300 |
| abstractText | 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. |
