APOPTOSIS AND THE CELL-CYCLE

This brief review examines the strict relationships between cell apopt osis and G1 cyclins. It has been shown that the basic role of G1 cycli ns is in regulating G1 progression and G1/S transition (the critical c ycle point for cell program decisions, including apoptosis) a fatal pr ogram for cells unable to bypass G1/S checkpoint 1. Notably, both of t he two giant regulators of checkpoint 1 (i.e., p105RB [retinoblastoma oncosuppressor-encoded protein] and p53 dependent WAF1/CIP1) are influ enced by or influence G1 cyclins: cyclin E/cdk2 kinase complexes hyper phosphorylate p105RB, induce E2F release, and free G1 exit. On the oth er hand, p21-WAF1/CIP1 is an inhibitor of cyclin-dependent kinases blo cking cells at G1/S. Thus, G1 cyclin activity appears as a conditio si ne qua non for G1 exit and apoptosis escape.