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

Marta Muzio, Arul M. Chinnaiyan, Frank C. Kischkel, Karen O'Rourke, Andrej Shevchenko, Jian Ni, Carsten Scaffidi, James D. Bretz, Mei Zhang, Reiner Gentz, Matthias Mann, Peter H. Krammer, Marcus E. Peter, Vishva M. Dixit

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)817-827
Number of pages11
JournalCell
Volume85
Issue number6
DOIs
Publication statusPublished - Jun 14 1996

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Death Domain Receptor Signaling Adaptor Proteins
Caspase 1
Death Domain Receptors
Cysteine Proteases
Caspase 8
Tandem Mass Spectrometry
Mass spectrometry
Peptide Hydrolases
Chemical activation
Apoptosis
Proteins
polyacrylamide gels
Death Effector Domain

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex. / Muzio, Marta; Chinnaiyan, Arul M.; Kischkel, Frank C.; O'Rourke, Karen; Shevchenko, Andrej; Ni, Jian; Scaffidi, Carsten; Bretz, James D.; Zhang, Mei; Gentz, Reiner; Mann, Matthias; Krammer, Peter H.; Peter, Marcus E.; Dixit, Vishva M.

In: Cell, Vol. 85, No. 6, 14.06.1996, p. 817-827.

Research output: Contribution to journalArticle

Muzio, M, Chinnaiyan, AM, Kischkel, FC, O'Rourke, K, Shevchenko, A, Ni, J, Scaffidi, C, Bretz, JD, Zhang, M, Gentz, R, Mann, M, Krammer, PH, Peter, ME & Dixit, VM 1996, 'FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex', Cell, vol. 85, no. 6, pp. 817-827. https://doi.org/10.1016/S0092-8674(00)81266-0
Muzio, Marta ; Chinnaiyan, Arul M. ; Kischkel, Frank C. ; O'Rourke, Karen ; Shevchenko, Andrej ; Ni, Jian ; Scaffidi, Carsten ; Bretz, James D. ; Zhang, Mei ; Gentz, Reiner ; Mann, Matthias ; Krammer, Peter H. ; Peter, Marcus E. ; Dixit, Vishva M. / FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex. In: Cell. 1996 ; Vol. 85, No. 6. pp. 817-827.
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AU - Mann, Matthias

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