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PMID:8654923

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Citation

Xue, D, Shaham, S and Horvitz, HR (1996) The Caenorhabditis elegans cell-death protein CED-3 is a cysteine protease with substrate specificities similar to those of the human CPP32 protease. Genes Dev. 10:1073-83

Abstract

The Caenorhabditis elegans cell-death gene ced-3 encodes a protein similar to mammalian interleukin-1beta-converting enzyme (ICE), a cysteine protease implicated in mammalian apoptosis. We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. We developed an easy and general method for the purification of CED-3/ICE-like proteases and used this method to facilitate a comparison of the substrate specificities of four different purified cysteine proteases. We found that in its substrate preferences CED-3 was more similar to the mammalian CPP32 protease than to mammalian ICE or NEDD2/ICH-1 protease. Our results suggest that different mammalian CED-3/ICE-like proteases may have distinct roles in mammalian apoptosis and that CPP32 is a candidate for being a mammalian functional equivalent of CED-3.

Links

PubMed

Keywords

Amino Acid Sequence; Animals; Apoptosis/physiology; Base Sequence; Caenorhabditis elegans/enzymology; Caenorhabditis elegans Proteins; Caspase 1; Caspase 2; Caspase 3; Caspases; Cysteine Endopeptidases/chemistry; Cysteine Endopeptidases/isolation & purification; Cysteine Endopeptidases/metabolism; Escherichia coli/genetics; Helminth Proteins/chemistry; Helminth Proteins/isolation & purification; Helminth Proteins/metabolism; Humans; Molecular Sequence Data; Molecular Weight; Neurons/cytology; Oligopeptides; Protein Processing, Post-Translational; Proteins/chemistry; Proteins/metabolism; Substrate Specificity

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CAEEL:CED3

involved_in

GO:0030163: protein catabolic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:CED3

enables

GO:0004197: cysteine-type endopeptidase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:D3YT61

enables

GO:0004197: cysteine-type endopeptidase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:D3YT61

GO:0006508: proteolysis

ECO:0000314:

P

Figure 1B shows that CED-3 is a cysteine protease because when the mutant CED or an inhibitor was used, cleavage products were not present.

complete
CACAO 9327

CAEEL:D3YT61

involved_in

GO:0030163: protein catabolic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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