Cutting Edge: Autoantigen Ro52 Is an Interferon Inducible E3 Ligase That Ubiquitinates IRF-8 and Enhances Cytokine Expression in Macrophages | Zendy

Hee Jeong Kong | Zendy; David E. Anderson | Zendy; Chang Hoon Lee | Zendy; Moon Kyoo Jang | Zendy; Tomohiko Tamura | Zendy; Prafullakumar Tailor | Zendy; Hyun Kook Cho | Zendy; JaeHun Cheong | Zendy; Huabao Xiong | Zendy; Herbert C. Morse | Zendy; Keiko Ozato | Zendy

Open Access

Cutting Edge: Autoantigen Ro52 Is an Interferon Inducible E3 Ligase That Ubiquitinates IRF-8 and Enhances Cytokine Expression in Macrophages

Author(s) -

Hee Jeong Kong,

David E. Anderson,

Chang Hoon Lee,

Moon Kyoo Jang,

Tomohiko Tamura,

Prafullakumar Tailor,

Hyun Kook Cho,

JaeHun Cheong,

Huabao Xiong,

Herbert C. Morse,

Keiko Ozato

Publication year - 2007

Publication title -

the journal of immunology

Language(s) - English

Resource type - Journals

eISSN - 1550-6606

pISSN - 0022-1767

DOI - 10.4049/jimmunol.179.1.26

Subject(s) - ubiquitin ligase , interferon regulatory factors , innate immune system , microbiology and biotechnology , ectopic expression , transcription factor , biology , interferon , ubiquitin , irf1 , cytokine , immunology , immune system , chemistry , gene , genetics

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.

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