β-catenin:: molecular plasticity and drug design

The protein beta -catenin is an essential component of intercellular junctions and the Wnt growth factor signaling pathway. In many cancers, mutation of Writ pathway components leads to activation of oncogenes by the beta -catenin-Tcf transcription factor complex. This complex is therefore an attractive target for anti-cancer drugs, but any such compound must selectively interfere with the beta -catenin-Tcf complex without disrupting other essential interactions of beta -catenin. Recent structural and biochemical studies have probed the molecular basis of ligand interaction by beta -catenin, and highlighted the possibilities and challenges of designing inhibitors of the beta -catenin-Tcf complex.