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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Sequence
  • Apoptosis / physiology*
  • Breast Neoplasms
  • Caenorhabditis elegans Proteins
  • Carcinoma
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Caspase 8
  • Caspase 9
  • Caspases*
  • Cysteine Endopeptidases / chemistry
  • Cysteine Endopeptidases / genetics*
  • Cysteine Endopeptidases / metabolism
  • Cysteine Proteinase Inhibitors / pharmacology
  • Fas-Associated Death Domain Protein
  • Granzymes
  • Helminth Proteins / chemistry
  • Helminth Proteins / genetics
  • Humans
  • Molecular Sequence Data
  • Organ Specificity
  • Protein Binding
  • RNA, Messenger / analysis
  • Sequence Analysis
  • Sequence Homology, Amino Acid
  • Serine Endopeptidases
  • Signal Transduction / physiology
  • Tumor Cells, Cultured
  • fas Receptor / physiology*

Substances

  • Adaptor Proteins, Signal Transducing
  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Cysteine Proteinase Inhibitors
  • FADD protein, human
  • Fas-Associated Death Domain Protein
  • Helminth Proteins
  • RNA, Messenger
  • fas Receptor
  • GZMB protein, human
  • Granzymes
  • Serine Endopeptidases
  • CASP8 protein, human
  • CASP9 protein, human
  • Caspase 8
  • Caspase 9
  • Caspases
  • Cysteine Endopeptidases
  • ced-3 protein, C elegans

Associated data

  • GENBANK/U58143