Roles of cyclin D1 and related genes in growth inhibition, senescence and apoptosis

It is now apparent that apoptosis is closely linked to the control of cell cycle progression. During the G1 to S progression, cyclin D1, p53, and the cyclin dependent kinase inhibitors p21(WAF1) and p27(kip1) can play roles i n induction of apoptosis. During the G2 and M phases, premature activation of Cdk1 can cause cells to enter mitotic catastrophe, which results in apop tosis. In this review we focus on factors acting during G1 and S, particula rly cyclin D1, and their effects on cell growth, senescence and apoptosis. We emphasize that cyclin D1 can have diverse effects on cells depending on its level of expression, the specific cell type, the cell context and other factors. Possible mechanisms by which cyclin D1 exerts these diverse effec ts, via cyclin dependent kinase-dependent and -independent pathways, are di scussed.