Cutting edge: autoantigen Ro52 is an interferon inducible E3 ligase that ubiquitinates IRF-8 and enhances cytokine expression in macrophages.
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.
Kong
Hee Jeong
HJ
Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, 6 Center Drive, Bethesda, MD 20892, USA.
Anderson
D Eric
DE
Lee
Chang Hoon
CH
Jang
Moon Kyoo
MK
Tamura
Tomohiko
T
Tailor
Prafullakumar
P
Cho
Hyun Kook
HK
Cheong
JaeHun
J
Xiong
Huabao
H
Morse
Herbert C
HC
Ozato
Keiko
K
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
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