2. Academic Validation
  3. FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death--inducing signaling complex

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

  • Cell. 1996 Jun 14;85(6):817-27. doi: 10.1016/s0092-8674(00)81266-0.
M Muzio 1,  A M Chinnaiyan,  F C Kischkel,  K O'Rourke,  A Shevchenko,  J Ni,  C Scaffidi,  J D Bretz,  M Zhang,  R Gentz,  M Mann,  P H Krammer,  M E Peter,  V M Dixit
Affiliations

Affiliation

  • 1 University of Michigan Medical School Department of Pathology, Ann Arbor, Michigan 48109, USA.
PMID: 8681377 DOI: 10.1016/s0092-8674(00)81266-0
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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