XB-ART-6281
Mol Cell
2002 Sep 01;103:563-71. doi: 10.1016/s1097-2765(02)00637-8.
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The crystal structure of the beta-catenin/ICAT complex reveals the inhibitory mechanism of ICAT.
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Beta-catenin is a multifunctional protein involved in both cell adhesion and transcriptional activation. Transcription mediated by the beta-catenin/Tcf complex is involved in embryological development and is upregulated in various cancers. We have determined the crystal structure at 2.5 A resolution of a complex between beta-catenin and ICAT, a protein that prevents the interaction between beta-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 beta-catenin. We show that ICAT selectively inhibits beta-catenin/Tcf binding in vivo, without disrupting beta-catenin/cadherin interactions. Thus, it should be possible to design cancer therapeutics that inhibit beta-catenin-mediated transcriptional activation without interfering with cell adhesion.
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Species referenced: Xenopus laevis
Genes referenced: ctnnbip1