Structure of a human Tcf4-beta-catenin complex

The multifunctional protein beta -catenin is important for cell adhesion, b ecause it binds cadherins, and the Wnt signal transduction pathway, where i t interacts with the Adenomatous polyposis coli (APC) protein and TCF/Lef f amily transcription factors. Mutations in APC or in beta -catenin are estim ated to trigger formation of over 90% of all colon cancers. In colonic epit helia, these mutations produce elevated levels of Tcf4-beta -catenin, which stimulates a transcriptional response that initiates polyp formation and e ventually malignant growth. Thus, disruption of the Tcf4-beta -catenin inte raction may be an attractive goal for therapeutic intervention. Here we des cribe the crystal structure of a human Tcf4-beta -catenin complex and compa re it with recent structures of beta -catenin in complex with Xenopus Tcf3 (XTcf3) and mammalian E-cadherin. The structure reveals anticipated similar ities with the closely related XTcf3 complex but unexpectedly lacks one com ponent observed in the XTcf3 structure.