Mechanistic insights from structural studies of beta-catenin and its binding partners.
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.
Xu
Wenqing
W
Department of Biological Structure, University of Washington, Seattle, WA 98195, USA. wxu@u.washington.edu
Kimelman
David
D
D022005:Adherens Junctions / Q000378:metabolism; D001665:Binding Sites; D015820:Cadherins / Q000737:chemistry / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D051176:beta Catenin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D015820:Cadherins; D046912:Multiprotein Complexes; D051176:beta Catenin