Involvement of retinoblastoma protein in p27Kip1-induced apoptosis.

p27Kip1, a cyclin-dependent kinase (CDK) inhibitor, plays a critical role in cell cycle regulation. Expression of p27Kip1 is shown to increase during apoptosis in mammalian cells. Here, to directly address the role of p27Kip1 in apoptosis, p27Kip1 is overexpressed in human SK-Hep1 hepatoma cells. This leads to apoptotic cell death and this reduces protein, but not mRNA, levels of the retinoblastoma (Rb). Consistently, accumulation of Rb protein blocks p27Kip1-mediated apoptosis. These studies demonstrate an involvement of Rb in the apoptotic cell death which is induced by overexpression of p27Kip1.