INCREASED P34(CDC2)-DEPENDENT KINASE-ACTIVITY DURING APOPTOSIS - A POSSIBLE ACTIVATION MECHANISM OF DNASE-I LEADING TO DNA BREAKDOWN

Cells undergoing apoptosis typically exhibit distinctive morphological characteristics. Early events include the rounding up of the cell, ch romatin condensation, nuclear membrane breakdown and blebbing of the c ellular membrane. Strikingly similar changes take place in the cell cy cle progression, at the entry into mitosis, suggesting a link between mitosis and apoptosis. Here we show that expression of active p34(cdc2 ) at inappropriate phases during the cell cycle leads to morphological changes reminiscent of apoptosis, including DNA degradation. Cells co transfected with the active mutant of p34(cdc2) and DNase I displayed degraded DNA, which was absent in p34(cdc2) wild-type and DNase I-tran sfected cells, in spite of similar DNase activities. Upon induction of apoptosis in thymocytes, transient p34(cdc2) activation was detected prior to lamina breadkdown and nuclease activation. P34(cdc2) activati on was also observed during APO-1 (Fas/CD95)-induced apoptosis in a B lymphoblastoma cell line. Our results suggest that unscheduled activat ion of p34(cdc2) may participate in the initiation of the typical apop totic phenotype.