دورية أكاديمية

Dynamic rewiring of the human interactome by interferon signaling

التفاصيل البيبلوغرافية
العنوان: Dynamic rewiring of the human interactome by interferon signaling
المؤلفون: 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.
المساهمون: Genome Canada, CIHR
المصدر: Genome Biology ; volume 21, issue 1 ; ISSN 1474-760X
بيانات النشر: Springer Science and Business Media LLC
سنة النشر: 2020
الوصف: 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.
نوع الوثيقة: article in journal/newspaper
اللغة: English
DOI: 10.1186/s13059-020-02050-y
DOI: 10.1186/s13059-020-02050-y.pdf
DOI: 10.1186/s13059-020-02050-y/fulltext.html
الإتاحة: https://doi.org/10.1186/s13059-020-02050-yTest
حقوق: https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test
رقم الانضمام: edsbas.EDDED7CC
قاعدة البيانات: BASE