Interleukin 1 beta converting enzyme-like proteases are essential for p53-mediated transcriptionally dependent apoptosis.
Interleukin 1 beta converting enzyme-like proteases are essential for p53-mediated transcriptionally dependent apoptosis.
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发表时间：
1997-06
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通讯作者：
P. Sabbatini;J. Han;S. Chiou;D. Nicholson;E. White
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作者：
P. Sabbatini;J. Han;S. Chiou;D. Nicholson;E. White
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.
