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.
read more
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.
read more
Chat with Paper
AI Agents for this Paper
Find similar papers on Google Scholar, PubMed and Arxiv
Write a critical review of this paper
Analyze citations of this paper to find unaddressed research gaps
Citations
The IL-1 family of cytokines. Do they have a role in scleroderma fibrosis?
TL;DR: Understanding how these cytokines are regulated and how they contribute to fibrosis will be important to understanding this pathology and may shed light in new areas for therapeutic development.
Proteases, proteolysis, and apoptosis.
TL;DR: The recent demonstration that protease inhibitors can rescue mice undergoing acute liver destruction indicates the accuracy of therapeutic strategies aiming to inhibit cell death-associated proteolysis, as well as confirming the role of proteolytic pathways in apoptosis.
Detection of soluble human granzyme K in vitro and in vivo
Britta Bade,Jens Lohrmann,Anja ten Brinke,Angela M. Wolbink,Gertjan Wolbink,Ineke J. M. ten Berge,J. Christian Virchow,Werner Luttmann,C. Erik Hack +8 more
TL;DR: It is concluded that GzmK protein is produced by cytotoxic cells, and just as GzmA and B it can be released in a soluble form into the extracellular space.
Converting enzyme-independent release of tumor necrosis factor α and IL-1β from a stimulated human monocytic cell line in the presence of activated neutrophils or purified proteinase 3
Claire Coeshott,Christie Ohnemus,Anna Pilyavskaya,Sherman E. Ross,Maciej Wieczorek,Heather Kroona,Axel H. Leimer,John C. Cheronis +7 more
TL;DR: There may be alternative pathways for the production of these two proinflammatory cytokines, particularly in the context of local inflammatory processes, according to results.
A novel RNA‐based adjuvant combines strong immunostimulatory capacities with a favorable safety profile
Regina Heidenreich,Edith Jasny,Aleksandra Kowalczyk,Johannes Lutz,Jochen Probst,Patrick Baumhof,Birgit Scheel,Söhnke Voss,Karl-Josef Kallen,Mariola Fotin-Mleczek +9 more
TL;DR: It is demonstrated that a recently developed novel adjuvant based on a non‐coding, long‐chain RNA molecule, termed RNAdjuvant®, profoundly increased immunogenicity of both antigen formats.
References
A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes.
Nancy A. Thornberry,Herbert G. Bull,Jimmy R. Calaycay,Kevin T. Chapman,Andrew D. Howard,Matthew J. Kostura,Douglas K. Miller,Susan M. Molineaux,Jeffrey R. Weidner,John G. Aunins,Keith O. Elliston,Julia M. Ayala,Francesca J. Casano,Jayne Chin,Gloria J.-F. Ding,Linda A. Egger,Erin P. Gaffney,Guadalupe A. Limjuco,Oksana C. Palyha,S.M. Raju,Anna M. Rolando,J. Paul Salley,Ting-Ting Yamin,Terry D. Lee,John E. Shively,Malcolm MacCross,Richard A. Mumford,John A. Schmidt,Michael J. Tocci +28 more
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.
2.7K
Molecular cloning and expression of the fas ligand, a novel member of the tumor necrosis factor family
TL;DR: Northern hybridization revealed that Fas ligand is expressed in activated splenocytes and thymocytes, consistent with its involvement in T cell-mediated cytotoxicity and in several nonlymphoid tissues, such as testis.
2.7K
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.
2.7K
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.
1.5K
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.
1.2K
Related Papers (5)
[...]
Nancy A. Thornberry,Herbert G. Bull,Jimmy R. Calaycay,Kevin T. Chapman,Andrew D. Howard,Matthew J. Kostura,Douglas K. Miller,Susan M. Molineaux,Jeffrey R. Weidner,John G. Aunins,Keith O. Elliston,Julia M. Ayala,Francesca J. Casano,Jayne Chin,Gloria J.-F. Ding,Linda A. Egger,Erin P. Gaffney,Guadalupe A. Limjuco,Oksana C. Palyha,S.M. Raju,Anna M. Rolando,J. Paul Salley,Ting-Ting Yamin,Terry D. Lee,John E. Shively,Malcolm MacCross,Richard A. Mumford,John A. Schmidt,Michael J. Tocci +28 more