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Dynamic rewiring of the human interactome by interferon signaling

BACKGROUND: The type I interferon (IFN) response is an ancient pathway that protects cells against viral pathogens by inducing the transcription of hundreds of IFN-stimulated genes. Comprehensive catalogs of IFN-stimulated genes have been established across species and cell types by transcriptomic a...

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Autores principales: Kerr, Craig H., Skinnider, Michael A., Andrews, Daniel D. T., Madero, Angel M., Chan, Queenie W. T., Stacey, R. Greg, Stoynov, Nikolay, Jan, Eric, Foster, Leonard J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294662/
https://www.ncbi.nlm.nih.gov/pubmed/32539747
http://dx.doi.org/10.1186/s13059-020-02050-y
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author Kerr, Craig H.
Skinnider, Michael A.
Andrews, Daniel D. T.
Madero, Angel M.
Chan, Queenie W. T.
Stacey, R. Greg
Stoynov, Nikolay
Jan, Eric
Foster, Leonard J.
author_facet Kerr, Craig H.
Skinnider, Michael A.
Andrews, Daniel D. T.
Madero, Angel M.
Chan, Queenie W. T.
Stacey, R. Greg
Stoynov, Nikolay
Jan, Eric
Foster, Leonard J.
author_sort Kerr, Craig H.
collection PubMed
description BACKGROUND: The type I interferon (IFN) response is an ancient pathway that protects cells against viral pathogens by inducing the transcription of hundreds of IFN-stimulated genes. Comprehensive catalogs of IFN-stimulated genes have been established across species and cell types by transcriptomic and biochemical approaches, but their antiviral mechanisms remain incompletely characterized. Here, we apply a combination of quantitative proteomic approaches to describe the effects of IFN signaling on the human proteome, and apply protein correlation profiling to map IFN-induced rearrangements in the human protein-protein interaction network. RESULTS: We identify > 26,000 protein interactions in IFN-stimulated and unstimulated cells, many of which involve proteins associated with human disease and are observed exclusively within the IFN-stimulated network. Differential network analysis reveals interaction rewiring across a surprisingly broad spectrum of cellular pathways in the antiviral response. We identify IFN-dependent protein-protein interactions mediating novel regulatory mechanisms at the transcriptional and translational levels, with one such interaction modulating the transcriptional activity of STAT1. Moreover, we reveal IFN-dependent changes in ribosomal composition that act to buffer IFN-stimulated gene protein synthesis. CONCLUSIONS: Our map of the IFN interactome provides a global view of the complex cellular networks activated during the antiviral response, placing IFN-stimulated genes in a functional context, and serves as a framework to understand how these networks are dysregulated in autoimmune or inflammatory disease.
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spelling pubmed-72946622020-06-16 Dynamic rewiring of the human interactome by interferon signaling Kerr, Craig H. Skinnider, Michael A. Andrews, Daniel D. T. Madero, Angel M. Chan, Queenie W. T. Stacey, R. Greg Stoynov, Nikolay Jan, Eric Foster, Leonard J. Genome Biol Research BACKGROUND: The type I interferon (IFN) response is an ancient pathway that protects cells against viral pathogens by inducing the transcription of hundreds of IFN-stimulated genes. Comprehensive catalogs of IFN-stimulated genes have been established across species and cell types by transcriptomic and biochemical approaches, but their antiviral mechanisms remain incompletely characterized. Here, we apply a combination of quantitative proteomic approaches to describe the effects of IFN signaling on the human proteome, and apply protein correlation profiling to map IFN-induced rearrangements in the human protein-protein interaction network. RESULTS: We identify > 26,000 protein interactions in IFN-stimulated and unstimulated cells, many of which involve proteins associated with human disease and are observed exclusively within the IFN-stimulated network. Differential network analysis reveals interaction rewiring across a surprisingly broad spectrum of cellular pathways in the antiviral response. We identify IFN-dependent protein-protein interactions mediating novel regulatory mechanisms at the transcriptional and translational levels, with one such interaction modulating the transcriptional activity of STAT1. Moreover, we reveal IFN-dependent changes in ribosomal composition that act to buffer IFN-stimulated gene protein synthesis. CONCLUSIONS: Our map of the IFN interactome provides a global view of the complex cellular networks activated during the antiviral response, placing IFN-stimulated genes in a functional context, and serves as a framework to understand how these networks are dysregulated in autoimmune or inflammatory disease. BioMed Central 2020-06-15 /pmc/articles/PMC7294662/ /pubmed/32539747 http://dx.doi.org/10.1186/s13059-020-02050-y Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Kerr, Craig H.
Skinnider, Michael A.
Andrews, Daniel D. T.
Madero, Angel M.
Chan, Queenie W. T.
Stacey, R. Greg
Stoynov, Nikolay
Jan, Eric
Foster, Leonard J.
Dynamic rewiring of the human interactome by interferon signaling
title Dynamic rewiring of the human interactome by interferon signaling
title_full Dynamic rewiring of the human interactome by interferon signaling
title_fullStr Dynamic rewiring of the human interactome by interferon signaling
title_full_unstemmed Dynamic rewiring of the human interactome by interferon signaling
title_short Dynamic rewiring of the human interactome by interferon signaling
title_sort dynamic rewiring of the human interactome by interferon signaling
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294662/
https://www.ncbi.nlm.nih.gov/pubmed/32539747
http://dx.doi.org/10.1186/s13059-020-02050-y
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