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

Immunity ·Vol. 6 ·No. 6 ·1997-06-00 ·Pages 751-63

Shu HB, Halpin DR, Goeddel DV

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,physiology Caspase 3 Caspase 8 Caspase 9 Caspases Cloning, Molecular Cysteine Endopeptidases/chemistry,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

Chemicals

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

Authors & Affiliations

3 authors, click to expand affiliations / ORCID

Shu H B

Tularik, Incorporated, South San Francisco, California 94080, USA.

Halpin D R

Goeddel D V

Article Info

Journal

Immunity

Abbr.

Immunity

ISSN

1074-7613

DOI

10.1016/s1074-7613(00)80450-1

Published

1997-06-00

Pages

751-63

Language

English

Region

United States

NLM ID

9432918

Subset

Databases

GENBANK

AF010127

External Links

PubMed source DOI: 10.1016/s1074-7613(00)80450-1 View journal details

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

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