[HTML][HTML] FLICE, a novel FADD-homologous ICE/CED-3–like protease, is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex

M Muzio, AM Chinnaiyan, FC Kischkel, K O'Rourke… - Cell, 1996 - cell.com
To identify CAP3 and CAP4, components of the CD95 (Fas/APO-1) death-inducing signaling
complex, we utilized nano-electrospray tandem mass spectrometry, a recently developed
technique to sequence femtomole quantities of polyacrylamide gel–separated proteins.
Interestingly, CAP4 encodes a novel 55 kDa protein, designated FLICE, which has
homology to both FADD and the ICE/CED-3 family of cysteine proteases. FLICE binds to the
death effector domain of FADD and upon overexpression induces apoptosis that is blocked …
Abstract
To identify CAP3 and CAP4, components of the CD95 (Fas/APO-1) death-inducing signaling complex, we utilized nano-electrospray tandem mass spectrometry, a recently developed technique to sequence femtomole quantities of polyacrylamide gel–separated proteins. Interestingly, CAP4 encodes a novel 55 kDa protein, designated FLICE, which has homology to both FADD and the ICE/CED-3 family of cysteine proteases. FLICE binds to the death effector domain of FADD and upon overexpression induces apoptosis that is blocked by the ICE family inhibitors, CrmA and z-VAD-fmk. CAP3 was identified as the FLICE prodomain which likely remains bound to the receptor after proteolytic activation. Taken together, this is unique biochemical evidence to link a death receptor physically to the proapoptotic proteases of the ICE/CED-3 family.
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