Granzyme A is an interleukin 1 beta-converting enzyme.

Détails

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Etat: Public
Version: Final published version
Licence: CC BY-NC-SA 4.0
ID Serval
serval:BIB_21038A504A30
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Granzyme A is an interleukin 1 beta-converting enzyme.
Périodique
The Journal of experimental medicine
Auteur⸱e⸱s
Irmler M., Hertig S., MacDonald H.R., Sadoul R., Becherer J.D., Proudfoot A., Solari R., Tschopp J.
ISSN
0022-1007
Statut éditorial
Publié
Date de publication
1995
Peer-reviewed
Oui
Volume
181
Numéro
5
Pages
1917-1922
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
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.
Mots-clé
Amino Acid Sequence, Apoptosis, Caspase 1, Cysteine Endopeptidases/metabolism, Granzymes, Humans, Interleukin-1/metabolism, Molecular Sequence Data, Protein Precursors/metabolism, Serine Endopeptidases/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 15:19
Dernière modification de la notice
20/08/2019 12:57
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