TRIM35 negatively regulates TLR7- and TLR9-mediated type I interferon production by targeting IRF7

  • FEBS Lett. 2015 May 22;589(12):1322-30. doi: 10.1016/j.febslet.2015.04.019.
Yanming Wang  1 ,  Shanshan Yan  1 ,  Bo Yang  1 ,  Yan Wang  2 ,  Haiyan Zhou  3 ,  Qiaoshi Lian  3 ,  Bing Sun  4
Affiliations
  • 1. School of Life Sciences, University of Science and Technology of China, Hefei, China.
  • 2. Key Laboratory of Molecular Virology & Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
  • 3. Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
  • 4. Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. Electronic address: [email protected].
PMID: 25907537 DOI: 10.1016/j.febslet.2015.04.019
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.

Keywords
Feedback regulation; IRF7; K48-linked ubiquitination; Proteasome-dependent degradation; TLR7/9; TRIM35.