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.
Keywords
FADDCaspaseCaspase 8Death domainCaspase 10NLRP1TRAF2BiologyApoptosisCell biologyProteasesCaspase 2Tumor necrosis factor alphaInhibitor of apoptosis domainCysteineFas receptorMolecular biologyProgrammed cell deathBiochemistryEnzymeImmunologyTumor necrosis factor receptor
MeSH Terms
Adaptor ProteinsSignal TransducingAmino Acid SequenceApoptosisCASP8 and FADD-Like Apoptosis Regulating ProteinCarrier ProteinsCaspase 3Caspase 8Caspase 9CaspasesCloningMolecularCysteine EndopeptidasesEndopeptidasesEnzyme InductionFas-Associated Death Domain ProteinHeLa CellsHumansIntracellular Signaling Peptides and ProteinsMolecular Sequence DataProtein BindingProtein ProcessingPost-TranslationalProteinsRecombinant ProteinsSequence AlignmentSequence DeletionSequence HomologyAmino AcidSerpinsSignal TransductionStructure-Activity RelationshipTNF Receptor-Associated Factor 1TNF Receptor-Associated Factor 2Tumor Necrosis Factor-alphaViral Proteinsfas Receptor
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Publication Info
- Year
- 1997
- Type
- article
- Volume
- 6
- Issue
- 6
- Pages
- 751-763
- Citations
- 396
- Access
- Closed
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Cite This
Hong‐Bing Shu,
David R Halpin,
David V. Goeddel
(1997).
Casper Is a FADD- and Caspase-Related Inducer of Apoptosis.
Immunity
, 6
(6)
, 751-763.
https://doi.org/10.1016/s1074-7613(00)80450-1
Identifiers
- DOI
- 10.1016/s1074-7613(00)80450-1
- PMID
- 9208847