ICAT Inhibits β-Catenin Binding to Tcf/Lef-Family Transcription Factors and the General Coactivator p300 Using Independent Structural Modules

• Autores: Danette L. Daniels, William I. Weis
• Localización: Molecular cell, ISSN 1097-2765, Vol. 9, Nº 3, 2002, págs. 573-584
• Idioma: inglés
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• Resumen

  • In the canonical Wnt signaling pathway, β-catenin activates target genes through its interactions with Tcf/Lef-family transcription factors and additional transcriptional coactivators. The crystal structure of ICAT, an inhibitor of β-catenin-mediated transcription, bound to the armadillo repeat domain of β-catenin, has been determined. ICAT contains an N-terminal helilical domain that binds to repeats 11 and 12 of β-catenin, and an extended C-terminal region that binds to repeats 5–10 in a manner similar to that of Tcfs and other β-catenin ligands. Full-length ICAT dissociates complexes of β-catenin, Lef-1, and the transcriptional coactivator p300, whereas the helical domain alone selectively blocks binding to p300. The C-terminal armadillo repeats of β-catenin may be an attractive target for compounds designed to disrupt aberrant β-catenin-mediated transcription associated with various cancers.