Casper is a FADD- and caspase-related inducer of apoptosis

Immunity. 1997 Jun;6(6):751-63. doi: 10.1016/s1074-7613(00)80450-1.

Abstract

Caspases are cysteine proteases that play a central role in apoptosis. Caspase-8 may be the first enzyme of the proteolytic cascade activated by the Fas ligand and tumor necrosis factor (TNF). Caspase-8 is recruited to Fas and TNF receptor-1 (TNF-R1) through interaction of its prodomain with the death effector domain (DED) of the receptor-associating FADD. Here we describe a novel 55 kDa protein, Casper, that has sequence similarity to caspase-8 throughout its length. However, Casper is not a caspase since it lacks several conserved amino acids found in all caspases. Casper interacts with FADD, caspase-8, caspase-3, TRAF1, and TRAF2 through distinct domains. When overexpressed in mammalian cells, Casper potently induces apoptosis. A C-terminal deletion mutant of Casper inhibits TNF- and Fas-induced cell death, suggesting that Casper is involved in these apoptotic pathways.

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Sequence
  • Apoptosis*
  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • Carrier Proteins / metabolism*
  • Carrier Proteins / physiology*
  • Caspase 3
  • Caspase 8
  • Caspase 9
  • Caspases*
  • Cloning, Molecular
  • Cysteine Endopeptidases / chemistry*
  • Cysteine Endopeptidases / metabolism
  • Endopeptidases / metabolism
  • Enzyme Induction
  • Fas-Associated Death Domain Protein
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Molecular Sequence Data
  • Protein Binding
  • Protein Processing, Post-Translational
  • Proteins / metabolism
  • Recombinant Proteins
  • Sequence Alignment
  • Sequence Deletion
  • Sequence Homology, Amino Acid
  • Serpins / metabolism
  • Signal Transduction
  • Structure-Activity Relationship
  • TNF Receptor-Associated Factor 1
  • TNF Receptor-Associated Factor 2
  • Tumor Necrosis Factor-alpha / physiology*
  • Viral Proteins*
  • fas Receptor / physiology*

Substances

  • Adaptor Proteins, Signal Transducing
  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • CFLAR protein, human
  • Carrier Proteins
  • FADD protein, human
  • Fas-Associated Death Domain Protein
  • Intracellular Signaling Peptides and Proteins
  • Proteins
  • Recombinant Proteins
  • Serpins
  • TNF Receptor-Associated Factor 1
  • TNF Receptor-Associated Factor 2
  • Tumor Necrosis Factor-alpha
  • Viral Proteins
  • fas Receptor
  • interleukin-1beta-converting enzyme inhibitor
  • Endopeptidases
  • CASP3 protein, human
  • CASP8 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 8
  • Caspase 9
  • Caspases
  • Cysteine Endopeptidases

Associated data

  • GENBANK/AF010127