Sequential activation of three distinct ICE-like activities in Fas-ligated Jurkat cells
EL Greidinger, DK Miller, TT Yamin, L Casciola-Rosen… - FEBS letters, 1996 - Elsevier
EL Greidinger, DK Miller, TT Yamin, L Casciola-Rosen, A Rosen
FEBS letters, 1996•ElsevierICE family proteases have been implicated as important effectors of the apoptotic pathway,
perhaps acting hierarchically in a protease cascade. Using cleavage of endogenous
protease substrates as probes, three distinct tiers of ICE-like activity were observed after Fas
ligation in Jurkat cells. The earliest cleavage detected (30 min) was of fodrin, and produced
a 150 kDa fragment. The second phase of cleavage (50 min) involved PARP, U1-70kDa and
DNA-PKcs, all substrates of the CPP32-like proteases. Lamin B cleavage was observed …
perhaps acting hierarchically in a protease cascade. Using cleavage of endogenous
protease substrates as probes, three distinct tiers of ICE-like activity were observed after Fas
ligation in Jurkat cells. The earliest cleavage detected (30 min) was of fodrin, and produced
a 150 kDa fragment. The second phase of cleavage (50 min) involved PARP, U1-70kDa and
DNA-PKcs, all substrates of the CPP32-like proteases. Lamin B cleavage was observed …
ICE family proteases have been implicated as important effectors of the apoptotic pathway, perhaps acting hierarchically in a protease cascade. Using cleavage of endogenous protease substrates as probes, three distinct tiers of ICE-like activity were observed after Fas ligation in Jurkat cells. The earliest cleavage detected (30 min) was of fodrin, and produced a 150 kDa fragment. The second phase of cleavage (50 min) involved PARP, U1-70kDa and DNA-PKcs, all substrates of the CPP32-like proteases. Lamin B cleavage was observed during the third cleavage phase (90 min). Distinct inhibition profiles obtained using a panel of peptide-based inhibitors of ICE-like proteases clearly distinguished the three different cleavage phases. These studies provide evidence for a sequence of ICE-like proteolytic activity during apoptosis. The early fodrin cleavage, producing a 150 kDa fragment, identifies an ICE-like activity proximal to CPP32 in Fas-induced Jurkat cell apoptosis.
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