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Title: Global functional profiling of human ubiquitome identifies E3 ubiquitin ligase DCST1 as a novel negative regulator of Type-I interferon signaling
Authors: Nair S. 
Bist P. 
Dikshit N. 
Krishnan M.N. 
Keywords: beta interferon
interferon regulatory factor
small interfering RNA
STAT2 protein
ubiquitin protein ligase
ubiquitinated protein
antagonists and inhibitors
drug effect
genetic transcription
HEK293 cell line
reporter gene
RNA interference
signal transduction
Computational Biology
Genes, Reporter
HEK293 Cells
Interferon Regulatory Factors
Interferon Type I
RNA Interference
RNA, Small Interfering
Signal Transduction
STAT2 Transcription Factor
Transcription, Genetic
Ubiquitin-Protein Ligases
Ubiquitinated Proteins
Issue Date: 2016
Publisher: Nature Publishing Group
Citation: Nair S., Bist P., Dikshit N., Krishnan M.N. (2016). Global functional profiling of human ubiquitome identifies E3 ubiquitin ligase DCST1 as a novel negative regulator of Type-I interferon signaling. Scientific Reports 6 : 36179. ScholarBank@NUS Repository.
Abstract: Type I interferon (IFN-I) mediated innate immune response controls virus infections by inducing the expression of interferon stimulated genes (ISGs). Although ubiquitination plays key roles in immune signaling regulation, a human genome-wide understanding of the role of E3 ubiquitin ligases in interferon mediated ISG induction is lacking. Here, we report a genome-wide profiling of the effect of ectopic expression of 521 E3 ubiquitin ligases and substrate recognition subunits encoded in the human genome (which constitutes 84.4% of all ubiquitination related genes encoded in the human genome, hereafter termed Human Ubiquitome) on IFN? mediated induction of interferon stimulated DNA response element (ISRE) driven reporter activity. We identified 96 and 42 genes of the human ubiquitome as novel negative and positive regulators of interferon signaling respectively. Furthermore, we characterized DCST1 as a novel E3 ubiquitin ligase negatively regulating interferon response. Ectopic expression and gene silencing of DCST1 respectively attenuated and increased ISRE reporter activity. DCST1 regulated Type I interferon signaling by interacting with and promoting ubiquitination-mediated degradation of STAT2, an essential component of antiviral gene induction. In summary, this study provided a systems level view on the role of human ubiquitination associated genes in Type I interferon response. © 2016 The Author(s).
Source Title: Scientific Reports
ISSN: 20452322
DOI: 10.1038/srep36179
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