Journal article
E. Gapud, M. I. Trejo-Zambrano, E. Gómez-Bañuelos, E. Tiniakou, B. Antiochos, D. Granville, F. Andrade, L. Casciola‐Rosen, A. Rosen
Journal of Immunology, 2020
Journal of Immunology, 2020
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APA
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Gapud, E., Trejo-Zambrano, M. I., Gómez-Bañuelos, E., Tiniakou, E., Antiochos, B., Granville, D., … Rosen, A. (2020). Granzyme B Induces IRF-3 Phosphorylation through a Perforin-Independent Proteolysis-Dependent Signaling Cascade without Inducing Cell Death. Journal of Immunology.
Chicago/Turabian
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Gapud, E., M. I. Trejo-Zambrano, E. Gómez-Bañuelos, E. Tiniakou, B. Antiochos, D. Granville, F. Andrade, L. Casciola‐Rosen, and A. Rosen. “Granzyme B Induces IRF-3 Phosphorylation through a Perforin-Independent Proteolysis-Dependent Signaling Cascade without Inducing Cell Death.” Journal of Immunology (2020).
MLA
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Gapud, E., et al. “Granzyme B Induces IRF-3 Phosphorylation through a Perforin-Independent Proteolysis-Dependent Signaling Cascade without Inducing Cell Death.” Journal of Immunology, 2020.
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@article{e2020a,
title = {Granzyme B Induces IRF-3 Phosphorylation through a Perforin-Independent Proteolysis-Dependent Signaling Cascade without Inducing Cell Death},
year = {2020},
journal = {Journal of Immunology},
author = {Gapud, E. and Trejo-Zambrano, M. I. and Gómez-Bañuelos, E. and Tiniakou, E. and Antiochos, B. and Granville, D. and Andrade, F. and Casciola‐Rosen, L. and Rosen, A.}
}
Abstract
Key Points GrB-induced intracellular cleavage and phosphorylation events do not need perforin. These cleavages and phosphorylations require GrB enzyme activity. DDR and IRF-3 phosphorylation are some of the functional results of these events. Granzyme B (GrB) is an immune protease implicated in the pathogenesis of several human diseases. In the current model of GrB activity, perforin determines whether the downstream actions of GrB occur intracellularly or extracellularly, producing apoptotic cytotoxicity or nonapoptotic effects, respectively. In the current study, we demonstrate the existence of a broad range of GrB-dependent signaling activities that 1) do not require perforin, 2) occur intracellularly, and 3) for which cell death is not the dominant outcome. In the absence of perforin, we show that GrB enzymatic activity still induces substoichiometric activation of caspases, which through nonlethal DNA damage response signals then leads to activity-associated phosphorylation of IFN regulatory factor–3. These findings illustrate an unexpected potential interface between GrB and innate immunity separate from the traditional role of GrB in perforin-dependent GrB-mediated apoptosis that could have mechanistic implications for human disease.
