E-Cadherin and APC Compete for the Interaction with β-Catenin and the Cytoskeleton

β-Catenin is involved in the formation of adherens junctions of mammalian epithelia. It interacts with the cell adhesion molecule E-cadherin and also with the tumor suppressor gene product APC, and the Drosophila homologue of β-catenin, armadillo, mediates morphogenetic signals. We demonstrate here that E-cadherin and APC directly compete for binding to the internal, armadillo-like repeats of β-catenin; the NH2-terminal domain of β-catenin mediates the interaction of the alternative E-cadherin and APC complexes to the cytoskeleton by binding to α-catenin. Plakoglobin (γ-catenin), which is structurally related to β-catenin, mediates identical interactions. We thus show that the APC tumor suppressor gene product forms strikingly similar associations as found in cell junctions and suggest that β-catenin and plakoglobin are central regulators of cell adhesion, cytoskeletal interaction, and tumor suppression.