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dc.contributor.authorHiggs, Rowan
dc.contributor.authorLazzari, Elisa
dc.contributor.authorWynne, Claire
dc.contributor.authorNí Gabhann, Joan
dc.contributor.authorEspinosa, Alexander
dc.contributor.authorWahren-Herlenius, Marie
dc.contributor.authorJefferies, Caroline A
dc.date.accessioned2010-11-17T12:46:59Z
dc.date.available2010-11-17T12:46:59Z
dc.date.issued2010
dc.identifier.citationSelf protection from anti-viral responses--Ro52 promotes degradation of the transcription factor IRF7 downstream of the viral Toll-Like receptors. 2010, 5 (7):e11776 PLoS ONEen
dc.identifier.issn1932-6203
dc.identifier.pmid20668674
dc.identifier.doi10.1371/journal.pone.0011776
dc.identifier.urihttp://hdl.handle.net/10147/115726
dc.description.abstractRo52 is a member of the TRIM family of single-protein E3 ligases and is also a target for autoantibody production in systemic lupus erythematosus and Sjögren's syndrome. We previously demonstrated a novel function of Ro52 in the ubiquitination and proteasomal degradation of IRF3 following TLR3/4 stimulation. We now present evidence that Ro52 has a similar role in regulating the stability and activity of IRF7. Endogenous immunoprecipitation of Ro52-bound proteins revealed that IRF7 associates with Ro52, an effect which increases following TLR7 and TLR9 stimulation, suggesting that Ro52 interacts with IRF7 post-pathogen recognition. Furthermore, we show that Ro52 ubiquitinates IRF7 in a dose-dependent manner, resulting in a decrease in total IRF7 expression and a subsequent decrease in IFN-alpha production. IRF7 stability was increased in bone marrow-derived macrophages from Ro52-deficient mice stimulated with imiquimod or CpG-B, consistent with a role for Ro52 in the negative regulation of IRF7 signalling. Taken together, these results suggest that Ro52-mediated ubiquitination promotes the degradation of IRF7 following TLR7 and TLR9 stimulation. As Ro52 is known to be IFN-inducible, this system constitutes a negative-feedback loop that acts to protect the host from the prolonged activation of the immune response.
dc.language.isoenen
dc.subjectIMMUNE SYSTEMen
dc.subjectGENETICSen
dc.subject.meshAnimals
dc.subject.meshCell Line
dc.subject.meshHela Cells
dc.subject.meshHumans
dc.subject.meshImmunoprecipitation
dc.subject.meshInterferon Regulatory Factor-7
dc.subject.meshInterferon-alpha
dc.subject.meshMice
dc.subject.meshMice, Knockout
dc.subject.meshProtein Binding
dc.subject.meshRibonucleoproteins
dc.subject.meshToll-Like Receptor 7
dc.subject.meshToll-Like Receptor 9
dc.subject.meshToll-Like Receptors
dc.subject.meshUbiquitination
dc.titleSelf protection from anti-viral responses--Ro52 promotes degradation of the transcription factor IRF7 downstream of the viral Toll-Like receptors.en
dc.typeArticleen
dc.contributor.departmentMolecular and Cellular Therapeutics and RSCI Research Institute, Royal College of Surgeons in Ireland, Dublin, Ireland.en
dc.identifier.journalPloS oneen
refterms.dateFOA2018-08-22T09:53:26Z
html.description.abstractRo52 is a member of the TRIM family of single-protein E3 ligases and is also a target for autoantibody production in systemic lupus erythematosus and Sjögren's syndrome. We previously demonstrated a novel function of Ro52 in the ubiquitination and proteasomal degradation of IRF3 following TLR3/4 stimulation. We now present evidence that Ro52 has a similar role in regulating the stability and activity of IRF7. Endogenous immunoprecipitation of Ro52-bound proteins revealed that IRF7 associates with Ro52, an effect which increases following TLR7 and TLR9 stimulation, suggesting that Ro52 interacts with IRF7 post-pathogen recognition. Furthermore, we show that Ro52 ubiquitinates IRF7 in a dose-dependent manner, resulting in a decrease in total IRF7 expression and a subsequent decrease in IFN-alpha production. IRF7 stability was increased in bone marrow-derived macrophages from Ro52-deficient mice stimulated with imiquimod or CpG-B, consistent with a role for Ro52 in the negative regulation of IRF7 signalling. Taken together, these results suggest that Ro52-mediated ubiquitination promotes the degradation of IRF7 following TLR7 and TLR9 stimulation. As Ro52 is known to be IFN-inducible, this system constitutes a negative-feedback loop that acts to protect the host from the prolonged activation of the immune response.


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