1. A License to Kill Cell Volume 85, Issue 6, Pages 781-784 (June 1996)
Andrew Fraser, Gerard Evan 
Cell 
Volume 85, Issue 6, Pages (June 1996)
DOI: /S (00)

2. Figure 1
Possible Model of Hierarchy of ICE-like Proteases in CD95/Fas/APO-1- and TNF-Induced Apoptosis
Ligand binding to CD95/Fas/APO-1 or to TNFR1 recruits FLICE/MACH1 to the plasma membrane via interaction with FADD. This recruitment of FLICE/MACH1 to either the CD95 or the TNFR1 signaling complexes somehow results in FLICE proteolytic activation, possibly through autocleavage. We suggest that ICE activity is required for amplification of the initial FLICE/MACH1 activation signal. However, ICE activity alone is not sufficient for triggering apoptosis; for this, the CPP32β/MCH2/MCH3/ICE-LAP6 subfamily of DEVD-cleaving proteases must finally be activated. This model is consistent with the fact that CD95 killing is blocked by inhibitors of either YVAD-specific (ICE-like) or DEVD-specific (CPP32β-like) proteases and that ICE (YVAD-specific) activity is detected early in the CD95 signaling pathway and is followed by later DEVD-specific activity.
Cell  , DOI: ( /S (00) )