Apoptosis-associated cleavage of β-catenin in human colon cancer and rat hepatoma cells

Abstract

Proteases belonging to the caspase family play a crucial role in apoptotic processes. Identification of protein cleavage specific to apoptosis may therefore provide further information about the mechanisms of apoptosis. In this study, apoptosis and necrosis were induced in cells of the human colon cancer cell lines, WiDr and DLD-1, and the resulting protein cleavage patterns investigated for β-catenin. β-Catenin was detected as a 92 kDa protein in control viable cells, while 65–72 kDa β-catenin cleavage fragments were characteristically observed in apoptotic cells. These fragments were not observed in necrotic cell death. Similar apoptosis-specific β-catenin cleavage was also demonstrated in the rat hepatoma cell line McA-RH7777, suggesting that the β-catenin cleavage is a common event in apoptosis in various cell types. The formation of 65–72 kDa β-catenin cleavage fragments was completely prevented by a caspase-1 inhibitor Z–VAD-CH2F and a caspase-3 inhibitor Z–DEVD-CH2F, indicating that the cleavage is associated with caspase-dependent process. Since β-catenin is implicated in cell adhesion and signal transduction, these findings may suggest various possible roles of β-catenin degradation in the dramatic cytoskeletal and morphological changes, as well as signaling events that accompany apoptosis.