Caspases and metalloproteinases may contribute to dissolution of adherens junctions during endothelial apoptosis. Initiation of apoptosis by growth factor deprivation of HUVEC leads to rapid dissolution of adherens junctions that may be mediated by metalloproteinase-dependent shedding of the extracellular domain of VE-cadherin and cleavage of β-catenin and plakoglobin that appear to involve caspases. A cleavage fragment of β-catenin (β′), but not plakoglobin (γ′), loses its ability to bind α-catenin, and, therefore, the intracellular connection of the adherens junction to the actin cytoskeleton is altered. These rapid intracellular and extracellular modifications of the adherens junctions impair cell–cell contact and result in intracellular disruption of the cytoskeleton.