CDK4, a possible critical regulator of apoptosis in rat pheochromocytoma PC12 cells

The function of cell cycle regulator molecules during apoptosis induced by serum withdrawal was examined in rat pheochromocytoma PC12 cells. When human cDNAs encoding cyclins, cyclin-dependent kinase 2 (CDK2), CDK4, and cell-division cycle 2 (CDC2), were introduced, only CDK4-overexpressing cells were more prone to apoptosis compared with parental cells. In the parental cells, serum withdrawal resulted in the upregulation of CDK4 protein expression 6.6-fold for the first 12 h after serum withdrawal. In contrast, CDK4 protein levels in CDK4-overexpressing cells remained constant for the first 12 h followed by a gradual decline. Expression of cyclin D1 was upregulated in both cell lines. The change in CDK4 kinase activity almost paralleled that of CDK4 protein expression. These results suggest that CDK4 kinase activity is one of the critical regulators in the apoptotic cascade in PC12 cells.