Granzyme A is an interleukin 1 beta-converting enzyme.
Martin Irmler,Sylvie Hertig,H R MacDonald,R. Sadoul,J. D. Becherer,A Proudfoot,Roberto Solari,Juerg Tschopp +7 more
TL;DR: It is concluded that the apoptosis-inducing granzyme A and ICE share at least one downstream target substrate, i.e., pIL-1 beta, which suggests that lymphocytes, by means of their own converting enzyme, could initiate a local inflammatory response independent of the presence of ICE.
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Abstract: Apoptosis is critically dependent on the presence of the ced-3 gene in Caenorhabditis elegans, which encodes a protein homologous to the mammalian interleukin (IL)-1 beta-converting enzyme (ICE). Overexpression of ICE or ced-3 promotes apoptosis. Cytotoxic T lymphocyte-mediated rapid apoptosis is induced by the proteases granzyme A and B. ICE and granzyme B share the rare substrate site of aspartic acid, after which amino acid cleavage of precursor IL-1 beta (pIL-1 beta) occurs. Here we show that granzyme A, but not granzyme B, converts pIL-1 beta to its 17-kD mature form. Major cleavage occurs at Arg120, four amino acids downstream of the authentic processing site, Asp116. IL-1 beta generated by granzyme A is biologically active. When pIL-1 beta processing is monitored in lipopolysaccharide-activated macrophage target cells attacked by cytotoxic T lymphocytes, intracellular conversion precedes lysis. Prior granzyme inactivation blocks this processing. We conclude that the apoptosis-inducing granzyme A and ICE share at least one downstream target substrate, i.e., pIL-1 beta. This suggests that lymphocytes, by means of their own converting enzyme, could initiate a local inflammatory response independent of the presence of ICE.
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A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes.
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TL;DR: Purification and cloning of the complementary DNA indicates that IL-lβ-converting enzyme is composed of two nonidentical subunits that are derived from a single proenzyme, possibly by autoproteolysis.
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Molecular cloning and expression of the fas ligand, a novel member of the tumor necrosis factor family
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The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1β-converting enzyme
TL;DR: It is proposed that the CED-3 protein acts as a cysteine protease in the initiation of programmed cell death in C. elegans and that cysteINE proteases also function in programmed cell deaths in mammals.
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Induction of apoptosis in fibroblasts by IL-1β-converting enzyme, a mammalian homolog of the C. elegans cell death gene ced-3
TL;DR: The results suggest that ICE may function during mammalian development to cause programmed cell death.
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Molecular cloning of the interleukin-1 beta converting enzyme
Douglas P. Cerretti,Carl J. Kozlosky,Bruce Mosley,Nicole Nelson,Kirk P. Van Ness,Teresa A. Greenstreet,Carl J. March,Shirley R. Kronheim,Teresa Druck,Linda A. Cannizzaro,Kay Huebner,Roy A. Black +11 more
TL;DR: A complementary DNA encoding a protease that carries out this cleavage has been cloned in this paper, and the gene encoding the protease was mapped to chromosomal band 11q23, a site frequently involved in rearrangement in human cancers.
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