Resumen de The Crystal Structure of the β-Catenin/ICAT Complex Reveals the Inhibitory Mechanism of ICAT.
Thomas A. Graham, David Kimelman, Wilson K. Clements
β-catenin is a multifunctional protein involved in both cell adhesion and transcriptional activation. Transcription mediated by the β-catenin/Tcf complex is involved in embryological development and is upregulated in various cancers. We have determined the crystal structure at 2.5 Å resolution of a complex between β-catenin and ICAT, a protein that prevents the interaction between β-catenin and Tcf/Lef family transcription factors. ICAT contains a 3-helix bundle that binds armadillo repeats 10–12 and a C-terminal tail that, similar to Tcf and E-cadherin, binds in the groove formed by armadillo repeats 5–9 of β-catenin. We show that ICAT selectively inhibits β-catenin/Tcf binding in vivo, without disrupting β-catenin/cadherin interactions. Thus, it should be possible to design cancer therapeutics that inhibit β-catenin-mediated transcriptional activation without interfering with cell adhesion.
