Apoptosis-associated cleavage of beta-catenin in human colon cancer and rat hepatoma cells.
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 beta-catenin. beta-Catenin was detected as a 92 kDa protein in control viable cells, while 65-72 kDa beta-catenin cleavage fragments were characteristically observed in apoptotic cells. These fragments were not observed in necrotic cell death. Similar apoptosis-specific beta-catenin cleavage was also demonstrated in the rat hepatoma cell line McA-RH7777, suggesting that the beta-catenin cleavage is a common event in apoptosis in various cell types. The formation of 65-72 kDa beta-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 beta-catenin is implicated in cell adhesion and signal transduction, these findings may suggest various possible roles of beta-catenin degradation in the dramatic cytoskeletal and morphological changes, as well as signaling events that accompany apoptosis.
Fukuda
K
K
Department of Oriental Medicine, Gifu University School of Medicine, Japan. kfukuda@cc.gifu-u.ac.jp
D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002087:Butyrates / Q000494:pharmacology; D015820:Cadherins / Q000378:metabolism; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D053938:DNA Fragmentation; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D015151:Immunoblotting; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D009336:Necrosis; D011480:Protease Inhibitors / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D015534:Trans-Activators; D051176:beta Catenin
D000199:Actins; D002087:Butyrates; C495270:CTNNB1 protein, human; D015820:Cadherins; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D006877:Hydroxamic Acids; D011480:Protease Inhibitors; D015534:Trans-Activators; D051176:beta Catenin; C012589:trichostatin A