Different effects of p58PITSLRE on the apoptosis induced by etoposide,cycloheximide and serum-withdrawal in human hepatocarcinoma cells

Minimal overexpression of the p58^PITSLRE protein kinase in Chinese hamster ovary cells induces telephase delay, abnormal cytokinesis, retarded cell growth and apoptosis. Fas mediated T cell death is correlated with p58^PITSLRE proteolysis and an increase in its histone H1 kinase activity. In this study, it was found that p58^PITSLRE had different effects on the apoptosis induced by etoposide, cycloheximide and serum-withdrawal in human hepatocarcinoma cells. The ectopic expression of p58^PITSLRE in human hepatocarcinoma cells suppressed apoptosis induced by etoposide, while enhancing the apoptosis induced by cycloheximide and serum-withdrawal respectively. Elevated expression of p58^PITSLRE was found during the apoptosis induced by etoposide, whereas most of p58^PITSLRE was proteolytically processed during apoptosis induced by cycloheximide and serum-withdrawal. Furthermore, transient transfection of p50^PITSLRE resembling the proteolytic form of p58^PITSLRE enhanced the 7721 cells susceptibility to apoptosis induced by all the three stimuli. These findings suggest that the full-length p58^PITSLRE might protect the cells from the apoptosis induced by etoposide and its proteolysis might contribute to and enhance the apoptosis induced by cycloheximide and serum-withdrawal respectively.