Interleukin 1 beta converting enzyme-like proteases are essential for p53-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. Coexpression of the E1B 19K protein in BRK cell lines transformed by E1A and p53(val135) rescues cells from p53-mediated apoptosis, and this is paralleled by the absence of both lamin and poly(ADP-ribose) polymerase cleavage. Therefore, the role of interleukin 1 beta converting enzyme (ICE)-like porteases in p53-mediated, transcriptionally dependent apoptosis was investigated. The ICE-like protease CPP32 was proteolytically activated during p53-mediated apoptosis in BRK cells, and this required a transcriptionally competent p53. Substitution of the p53 transactivation domain with the transactivation domain of herpes simplex virus VP16 (VP16/p53) resulted in accelerated kinetics of both apoptosis and Bax induction. Moreover, apoptosis induced by p53, VP16/p53, and 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 proteases.
Sabbatini
P
P
Center for Advanced Biotechnology and Medicine, Cancer Institute of New Jersey, Piscataway, USA.
Han
J
J
Chiou
S K
SK
Nicholson
D W
DW
White
E
E
D017500:Adenovirus E1A Proteins; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D020170:Caspase 1; D053148:Caspase 3; D020169:Caspases; D002461:Cell Line, Transformed; D002470:Cell Survival; D003546:Cysteine Endopeptidases / Q000502:physiology*; D004792:Enzyme Precursors / Q000502:physiology; D016158:Genes, p53 / Q000502:physiology*; D007668:Kidney / Q000166:cytology; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D015533:Transcriptional Activation; D014162:Transfection; D051028:bcl-2-Associated X Protein
D017500:Adenovirus E1A Proteins; C494827:Bax protein, mouse; C494828:Bax protein, rat; D004792:Enzyme Precursors; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C505409:Casp3 protein, mouse; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; D020170:Caspase 1