Potentiation of ceramide-induced apoptosis by p27kip1 overexpression.

The cyclin-dependent kinase inhibitor p27kip1 (p27) has been implicated in the regulation of cell cycle and apoptosis. Recently, we have demonstrated that ceramide induces apoptotic cell death associated with increase in the level of p27 in HL-60 cells. In the present study, we showed that overexpression of p27 increases ceramide-induced apoptotic cell death in HL-60 cells. Furthermore, overexpression of p27 accelerated DNA fragmentation, PARP cleavage and cytochrome c release induced by ceramide. In addition, ceramide induced Bax expression independent of p27. These findings indicate that enhanced effect on apoptosis by p27 is associated with mitochondrial signaling which involves cytochrome c release.