FINAL CHECKPOINT IN THE DRUG-PROMOTED AND POLIOVIRUS-PROMOTED APOPTOSIS IS UNDER POSTTRANSLATIONAL CONTROL BY GROWTH-FACTORS

The treatment of HeLa subline (HeLa-B) cells with cycloheximide or Act inomycin D resulted in a rapid (similar to 1.5 h and similar to 2.5 h, respectively) development of morphological and biochemical signs of a poptosis. The addition of fetal bovine serum to the cycloheximide-trea ted or Actinomycin D-treated cells suppressed the apoptotic reaction, as evidenced by the postponement of the DNA fragmentation for at least 9 and 5 h, respectively. A similar suppressive effect was observed up on the serum addition to cells undergoing abortive infection with poli ovirus, which died of apoptosis in the absence of the serum. The serum appeared to exert its anti-apoptotic effect without any appreciable l ag and even immediately blocked further progress of ongoing DNA fragme ntation. The epidermal growth factor also suppressed, although less ef ficiently and more transiently, the apoptotic reaction promoted by the metabolic inhibitors. It is concluded that growth factors may affect, without modulating either transcription or translation, the balance o f pro-apoptotic and anti-apoptotic activities at a final checkpoint, j ust preceding the irreversible effector step of apoptosis. (C) 1996 Wi ley-Liss, Inc.