INTERLEUKIN-1-BETA CONVERTING ENZYME-LIKE PROTEASES ARE ESSENTIAL FORP53-MEDIATED TRANSCRIPTIONALLY DEPENDENT APOPTOSIS

p53-mediated apoptosis in baby rat kidney (BRK) cell lines transformed by E1A and p53(val135) requires a transcriptionally functional p53. C oexpression of the E1B 19K protein in BRK cell lines transformed by E1 A and p53(val135) rescues cells from p53-mediated apoptosis, and this is paralleled by the absence of both lamin and poly(ADP-ribose) polyme rase cleavage, Therefore, the role of interleukin 1 beta converting en zyme (ICE)-like proteases in p53-mediated, transcriptionally dependent apoptosis was investigated, The ICE-like protease CPP32 was proteolyt ically activated during p53-mediated apoptosis in BRK cells, and this required a transcriptionally competent p53, Substitution of the p53 tr ansactivation domain with the transactivation domain of herpes simplex virus VP16 (VP16/p53) resulted in accelerated kinetics of both apopto sis and Bax induction, Moreover, apoptosis induced by p53, VP16/p53, a nd Bax was abrogated by Z-VAD.FMK, an inhibitor of ICE-like proteases. These results indicate that all apoptotic pathways downstream of p53- mediated transcription converge upon the activation of ICE-like protea ses.