Abstract
The multifunctional protein β-catenin is important for cell adhesion, because it binds cadherins, and the Wnt signal transduction pathway, where it interacts with the Adenomatous polyposis coli (APC) protein and TCF/Lef family transcription factors. Mutations in APC or in β-catenin are estimated to trigger formation of over 90% of all colon cancers. In colonic epithelia, these mutations produce elevated levels of Tcf4–β-catenin, which stimulates a transcriptional response that initiates polyp formation and eventually malignant growth. Thus, disruption of the Tcf4–β-catenin interaction may be an attractive goal for therapeutic intervention. Here we describe the crystal structure of a human Tcf4–β-catenin complex and compare it with recent structures of β-catenin in complex with Xenopus Tcf3 (XTcf3) and mammalian E-cadherin. The structure reveals anticipated similarities with the closely related XTcf3 complex but unexpectedly lacks one component observed in the XTcf3 structure.
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Poy, F., Lepourcelet, M., Shivdasani, R. et al. Structure of a human Tcf4–β-catenin complex. Nat Struct Mol Biol 8, 1053–1057 (2001). https://doi.org/10.1038/nsb720
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DOI: https://doi.org/10.1038/nsb720
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