Dynamic rewiring of the human interactome by interferon signaling.

Genome Biology
Craig H KerrLeonard J Foster

Abstract

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. 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...Continue Reading

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Citations

Nov 6, 2020·Molecular & Cellular Proteomics : MCP·R Greg StaceyLeonard J Foster
Feb 17, 2021·Molecular & Cellular Proteomics : MCP·R Greg StaceyLeonard J Foster
Mar 17, 2021·Biochimica Et Biophysica Acta. Bioenergetics·Joeri van StrienMartijn A Huynen
May 4, 2021·Biochimica Et Biophysica Acta. Bioenergetics·Hendrik Nolte, Thomas Langer
May 15, 2021·Molecular Cell·Sungyul LeeV Narry Kim
Jul 3, 2021·Cell·Michael A SkinniderLeonard J Foster
Nov 5, 2020·Analytical Chemistry·Jiangnan ZhengRuijun Tian

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Methods Mentioned

BETA
size exclusion chromatography
phylogenetic profile
phylogenetic profiles
exome sequencing
ubiquitination
immunoprecipitations
co-immunoprecipitations
co-immunoprecipitation
transfection
protein correlation profiling

Software Mentioned

R
WikiPathways
R package “ ppcor ”
R package “ ontologyIndex ”
SILAC
SEC
limma
InBioMap
ggnetwork
PINA

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