SUMO2 and SUMO3 redundantly prevent a noncanonical type I interferon response

Detection of nucleic acids by innate immune sensors triggers the production of type I interferons (IFNs). While IFNs are essential for host defense against viral infection, dysregulated production of IFNs underlies numerous autoinflammatory diseases. We have found that the loss of sumoylation result...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2018-06, Vol.115 (26), p.6798-6803
Main Authors: Crowl, John T., Stetson, Daniel B.
Format: Article
Language:English
Subjects:
Biological Sciences
Disease prevention
HEK293 Cells
Humans
Interferon
Interferon regulatory factor 3
Interferon regulatory factor 7
Interferon Regulatory Factor-3 - genetics
Interferon Regulatory Factor-3 - metabolism
Interferon Regulatory Factor-7 - genetics
Interferon Regulatory Factor-7 - metabolism
Interferon Type I - genetics
Interferon Type I - metabolism
Nucleic acids
Proteins
Regulators
Signal Transduction - physiology
Small Ubiquitin-Related Modifier Proteins - genetics
Small Ubiquitin-Related Modifier Proteins - metabolism
SUMO protein
Sumoylation - physiology
THP-1 Cells
Transcription factors
Ubiquitin
Ubiquitins - genetics
Ubiquitins - metabolism
Vertebrates
Viral infections
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Summary:Detection of nucleic acids by innate immune sensors triggers the production of type I interferons (IFNs). While IFNs are essential for host defense against viral infection, dysregulated production of IFNs underlies numerous autoinflammatory diseases. We have found that the loss of sumoylation results in a potent, spontaneous IFN response. Vertebrates possess three small ubiquitin-like modifiers (SUMOs) that can be conjugated onto target proteins and alter protein function in diverse but still poorly characterized ways. We demonstrate that regulation of IFN by sumoylation is redundantly mediated by both SUMO2 and SUMO3, but not SUMO1, revealing a previously unknown function of SUMO2/3. Remarkably, this IFN response is independent of all known IFN-inducing pathways and does not require either of the canonical IFN-associated transcription factors IRF3 or IRF7. Taken together, our findings demonstrate that SUMO2 and SUMO3 are specific and essential negative regulators of a noncanonical mechanism of IFN induction.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1802114115