Mechanistic insights from structural studies of beta-catenin and its binding partners

Abstract

Beta-catenin is both a crucial regulator of cell adhesion and the central effector of the canonical Wnt signaling pathway. It functions as a protein organizer by interacting with numerous partners at the membrane, in the cytosol, and in the nucleus. Recent structural and biochemical studies have revealed how beta-catenin engages in critical protein-protein interactions by using its armadillo repeat region and its N- and C-terminal domains. The groove in the armadillo repeat region is a particularly interesting feature of beta-catenin, since it serves as a common binding site for several beta-catenin-binding partners, with steric hindrance limiting which partners can be bound at a specific time. These studies provide important insights into beta-catenin-mediated mechanisms of cell adhesion and Wnt signaling and suggest potential approaches for the design of therapeutic agents to treat diseases caused by misregulated beta-catenin expression.