title: FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death--inducing signaling complex.
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.
authors.affiliation: University of Michigan Medical School Department of Pathology, Ann Arbor, Michigan 48109, USA.
authors.forename: M
authors.initials: M
authors.lastname: Muzio
authors.forename: A M
authors.initials: AM
authors.lastname: Chinnaiyan
authors.forename: F C
authors.initials: FC
authors.lastname: Kischkel
authors.forename: K
authors.initials: K
authors.lastname: O'Rourke
authors.forename: A
authors.initials: A
authors.lastname: Shevchenko
authors.forename: J
authors.initials: J
authors.lastname: Ni
authors.forename: C
authors.initials: C
authors.lastname: Scaffidi
authors.forename: J D
authors.initials: JD
authors.lastname: Bretz
authors.forename: M
authors.initials: M
authors.lastname: Zhang
authors.forename: R
authors.initials: R
authors.lastname: Gentz
authors.forename: M
authors.initials: M
authors.lastname: Mann
authors.forename: P H
authors.initials: PH
authors.lastname: Krammer
authors.forename: M E
authors.initials: ME
authors.lastname: Peter
authors.forename: V M
authors.initials: VM
authors.lastname: Dixit
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D017209:Apoptosis / Q000502:physiology*; D001943:Breast Neoplasms; D029742:Caenorhabditis elegans Proteins; D002277:Carcinoma; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D053200:Fas-Associated Death Domain Protein; D053804:Granzymes; D015801:Helminth Proteins / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009928:Organ Specificity; D011485:Protein Binding; D012333:RNA, Messenger / Q000032:analysis; D017421:Sequence Analysis; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases; D015398:Signal Transduction / Q000502:physiology; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D015853:Cysteine Proteinase Inhibitors; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D015801:Helminth Proteins; D012333:RNA, Messenger; D019014:fas Receptor; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D003546:Cysteine Endopeptidases; C089223:ced-3 protein, C elegans