Apoptosis and the cell cycle

This brief review examines the strict relationships between cell apoptosis and G1 cyclins. It has been shown that the basic role of G1 cyclins is in regulating G1 progression and G1/S transition (the critical cycle point for cell program decisions, including apoptosis) a fatal program for cells unable to bypass G1/S checkpoint 1. Notably, both of the two giant regulators of checkpoint 1 (i.e., p105RB [retinoblastoma oncosuppressor-encoded protein] and p53 dependent WAF1/CIP1) are influenced by or influence G1 cyclins: cyclin E/cdk2 kinase complexes hyperphosphorylate p105RB, induce E2F release, and free G1 exit. On the other hand, p21-WAF1/CIP1 is an inhibitor of cyclin-dependent kinases blocking cells at G1/S. Thus, G1 cyclin activity appears as a conditio sine qua non for G1 exit and apoptosis escape.