STAT2 is an essential adaptor in USP18-mediated suppression of type I interferon signaling.
Type I interferons (IFNs) are multifunctional cytokines that regulate immune responses and cellular functions but also can have detrimental effects on human health. A tight regulatory network therefore controls IFN signaling, which in turn may interfere with medical interventions. The JAK-STAT signaling pathway transmits the IFN extracellular signal to the ... nucleus, thus resulting in alterations in gene expression. STAT2 is a well-known essential and specific positive effector of type I IFN signaling. Here, we report that STAT2 is also a previously unrecognized, crucial component of the USP18-mediated negative-feedback control in both human and mouse cells. We found that STAT2 recruits USP18 to the type I IFN receptor subunit IFNAR2 via its constitutive membrane-distal STAT2-binding site. This mechanistic coupling of effector and negative-feedback functions of STAT2 may provide novel strategies for treatment of IFN-signaling-related human diseases.
Mesh Terms:
Animals, Cell Line, Tumor, Endopeptidases, Feedback, Physiological, Humans, Immunoblotting, Interferon Type I, Mice, Mutant Proteins, Protein Binding, Protein Domains, Receptor, Interferon alpha-beta, STAT2 Transcription Factor, Signal Transduction, Two-Hybrid System Techniques
Animals, Cell Line, Tumor, Endopeptidases, Feedback, Physiological, Humans, Immunoblotting, Interferon Type I, Mice, Mutant Proteins, Protein Binding, Protein Domains, Receptor, Interferon alpha-beta, STAT2 Transcription Factor, Signal Transduction, Two-Hybrid System Techniques
Nat. Struct. Mol. Biol.
Date: Dec. 01, 2016
PubMed ID: 28165510
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