TRIM35 negatively regulates TLR7‐ and TLR9‐mediated type I interferon production by targeting IRF7. Issue 12 (20th April 2015)

• Record Type: Journal Article
• Authors: Wang, Yanming; Yan, Shanshan; Yang, Bo; Wang, Yan; Zhou, Haiyan; Lian, Qiaoshi; Sun, Bing
• Is Part Of: FEBS letters. Volume 589:Issue 12(2015)
• Page Start: 1322
• Page End: 1330
• Publication Date: 2015-04-20
• Subjects: TRIM35 -- TLR7/9 -- IRF7 -- K48-linked ubiquitination -- Proteasome-dependent degradation -- Feedback regulation; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2015.04.019
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : Toll‐like receptor 7 (TLR7) and TLR9 sense viral nucleic acids and induce type I IFN production, which must be properly controlled to avoid autoimmune diseases. Here, we report the negative regulation of TLR7/9‐mediated type I IFN production by TRIM35. TRIM35 expression is induced by TLR7/9 stimulation and then interacts with IRF7, which is the master regulator of type I IFN response. Furthermore, TRIM35 promotes the K48‐linked ubiquitination of IRF7 and induces its degradation via a proteasome‐dependent pathway. Therefore, TRIM35 is a negative feedback regulator of TLR7/9‐mediated type I IFN production due to its ability to suppress the stability of IRF7. Abstract : TRIM35 expression is induced by TLR7/9 ligand stimulation. Knockdown of TRIM35 enhances type I IFN production following TLR7/9 stimulation. TRIM35 interacts with IRF7 and induces the K48‐linked ubiquitination of it. TRIM35 promotes the degradation of IRF7 via a ubiquitin‐proteasome pathway.