Abstract
IFN regulatory factor (IRF)-8 is a transcription factor important for the development and function of macrophages. It plays a critical role in the induction of cytokine genes, including IL-12p40. Immunopurification and mass spectrometry analysis found that IRF-8 interacted with Ro52 in murine macrophages upon IFN-gamma and TLR stimulation. Ro52 is an IFN-inducible protein of the tripartite motif (TRIM) family and is an autoantigen present in patients with Sjögren's syndrome and systemic lupus erythematosus. Ro52 has a RING motif and is capable of ubiquitinating itself. We show that IRF-8 is ubiquitinated by Ro52 both in vivo and in vitro. Ectopic expression of Ro52 enhanced IL-12p40 expression in IFN-gamma/TLR-stimulated macrophages in an IRF-8-dependent manner. Together, Ro52 is an E3 ligase for IRF-8 that acts in a non-degradation pathway of ubiquitination, and contributes to the elicitation of innate immunity in macrophages.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Animals
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Autoantigens / chemistry
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Autoantigens / metabolism
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Autoantigens / physiology
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Cell Line
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Cytokines / biosynthesis*
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Immunity, Innate
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Interferon Regulatory Factors / chemistry
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Interferon Regulatory Factors / metabolism*
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Interferon-gamma / physiology*
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Macrophage Activation / immunology
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Macrophages / enzymology
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Macrophages / immunology*
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Macrophages / metabolism
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Mice
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Protein Structure, Tertiary
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Ribonucleoproteins / chemistry
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Ribonucleoproteins / metabolism
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Ribonucleoproteins / physiology*
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Signal Transduction / immunology
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Toll-Like Receptors / physiology
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Ubiquitin / metabolism*
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Ubiquitin-Protein Ligases / biosynthesis
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Ubiquitin-Protein Ligases / physiology*
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Up-Regulation / immunology*
Substances
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Autoantigens
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Cytokines
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Interferon Regulatory Factors
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Ribonucleoproteins
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SS-A antigen
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Toll-Like Receptors
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Ubiquitin
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interferon regulatory factor-8
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Interferon-gamma
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Ubiquitin-Protein Ligases