title: Cutting edge: autoantigen Ro52 is an interferon inducible E3 ligase that ubiquitinates IRF-8 and enhances cytokine expression in macrophages.
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.
authors.affiliation: Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, 6 Center Drive, Bethesda, MD 20892, USA.
authors.forename: Hee Jeong
authors.initials: HJ
authors.lastname: Kong
authors.forename: D Eric
authors.initials: DE
authors.lastname: Anderson
authors.forename: Chang Hoon
authors.initials: CH
authors.lastname: Lee
authors.forename: Moon Kyoo
authors.initials: MK
authors.lastname: Jang
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Tamura
authors.forename: Prafullakumar
authors.initials: P
authors.lastname: Tailor
authors.forename: Hyun Kook
authors.initials: HK
authors.lastname: Cho
authors.forename: JaeHun
authors.initials: J
authors.lastname: Cheong
authors.forename: Huabao
authors.initials: H
authors.lastname: Xiong
authors.forename: Herbert C
authors.initials: HC
authors.lastname: Morse
authors.forename: Keiko
authors.initials: K
authors.lastname: Ozato
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis*; D007113:Immunity, Innate; D050835:Interferon Regulatory Factors / Q000737:chemistry / Q000378:metabolism*; D007371:Interferon-gamma / Q000502:physiology*; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D017434:Protein Structure, Tertiary; D012261:Ribonucleoproteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology; D051193:Toll-Like Receptors / Q000502:physiology; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis / Q000502:physiology*; D015854:Up-Regulation / Q000276:immunology*; D000099207:SS-A Antigen; D000099185:Interferon Regulatory Factor-8
chemical_list: D001324:Autoantigens; D016207:Cytokines; D050835:Interferon Regulatory Factors; D007371:Interferon-gamma; D012261:Ribonucleoproteins; D051193:Toll-Like Receptors; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D000099207:SS-A Antigen; D000099185:Interferon Regulatory Factor-8