Specific cleavage of gamma catenin by caspases during apoptosis.
Caspase-mediated proteolysis of cytoskeletal proteins during apoptosis appears to be commonplace. Enlarging on previous studies we have shown here that gamma catenin, like beta catenin, was degraded during cisplatin-induced apoptosis, initially giving a major product of 75 kDa. This truncated protein could be co-immunoprecipitated with alpha catenin. Addition of caspase inhibitors to cells in the presence of cisplatin appreciably reduced the proteolysis of gamma catenin as well as the level of apoptosis. Only limited degradation of alpha catenin was observed even at very late times when over 90% of cells in the culture were apoptotic. Immunohistochemical staining showed that during apoptosis there was a relocation of alpha, beta, and gamma catenin from the periphery of the cell to the cytoplasm, at the same time as other morphological changes commonly associated with apoptosis occurred. Interestingly, the changes in localisation of the catenins preceded proteolysis by several hours. In the presence of cisplatin and caspase inhibitor no change in distribution of catenins was observed, suggesting that re-localisation requires caspase activity but not necessarily directed against beta and gamma catenins.
Schmeiser
K
K
CRC Institute for Cancer Studies, University of Birmingham, Edgbaston, UK.
Hammond
E M
EM
Roberts
S
S
Grand
R J
RJ
D017500:Adenovirus E1A Proteins / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D002945:Cisplatin / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000378:metabolism*; D051180:Desmoplakins; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D007163:Immunosorbent Techniques; D051381:Rats; D012160:Retina; D014162:Transfection; D014407:Tumor Cells, Cultured; D051178:alpha Catenin; D051185:gamma Catenin
D017500:Adenovirus E1A Proteins; C495273:CTNNA1 protein, human; D015853:Cysteine Proteinase Inhibitors; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D004791:Enzyme Inhibitors; C495292:JUP protein, human; D051178:alpha Catenin; D051185:gamma Catenin; D003546:Cysteine Endopeptidases; D002945:Cisplatin