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Nuclear RNF2 inhibits interferon function by promoting K33-linked STAT1 disassociation from DNA
- Source :
- Nature immunology. 19(1)
- Publication Year :
- 2017
-
Abstract
- Prolonged activation of interferon-STAT1 signaling is closely related to inflammatory autoimmune disorders, and therefore the identification of negative regulators of these pathways is important. Through high-content screening of 115 mouse RING-domain E3 ligases, we identified the E3 ubiquitin ligase RNF2 as a potent inhibitor of interferon-dependent antiviral responses. RNF2 deficiency substantially enhanced interferon-stimulated gene (ISG) expression and antiviral responses. Mechanistically, nuclear RNF2 directly bound to STAT1 after interferon stimulation and increased K33-linked polyubiquitination of the DNA-binding domain of STAT1 at position K379, in addition to promoting the disassociation of STAT1/STAT2 from DNA and consequently suppressing ISG transcription. Our study provides insight into the regulation of interferon-dependent responses via a previously unrecognized post-translational modification of STAT1 in the nucleus.
- Subjects :
- 0301 basic medicine
Transgene
Ubiquitin-Protein Ligases
Immunology
Gene Expression
Mice, Transgenic
Antiviral Agents
Vesicular stomatitis Indiana virus
Cell Line
03 medical and health sciences
0302 clinical medicine
Ubiquitin
Transcription (biology)
Interferon
medicine
Immunology and Allergy
Animals
STAT1
STAT2
Gene
Mice, Knockout
Polycomb Repressive Complex 1
biology
Chemistry
Lysine
Macrophages
Ubiquitination
STAT2 Transcription Factor
DNA
Ubiquitin ligase
Mice, Inbred C57BL
030104 developmental biology
STAT1 Transcription Factor
030220 oncology & carcinogenesis
Interferon Type I
biology.protein
Cancer research
Vesicular Stomatitis
medicine.drug
Protein Binding
Subjects
Details
- ISSN :
- 15292916
- Volume :
- 19
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature immunology
- Accession number :
- edsair.doi.dedup.....bd071f08e25a6ed665235471b01b9750