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

Yanming Wang; Shanshan Yan; Bo Yang; Yan Wang; Haiyan Zhou; Qiaoshi Lian; Bing Sun

doi:10.1016/j.febslet.2015.04.019

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. Epub 2015 Apr 20.

Authors

Yanming Wang¹, Shanshan Yan¹, Bo Yang¹, Yan Wang², Haiyan Zhou³, Qiaoshi Lian³, Bing Sun⁴

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: bsun@sibs.ac.cn.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis Regulatory Proteins / antagonists & inhibitors
Apoptosis Regulatory Proteins / genetics
Apoptosis Regulatory Proteins / metabolism*
Cell Line
Cells, Cultured
Dendritic Cells / immunology
Dendritic Cells / metabolism*
Down-Regulation*
Humans
Interferon Regulatory Factor-7 / metabolism*
Interferon Type I / biosynthesis*
Ligands
Membrane Glycoproteins / agonists
Membrane Glycoproteins / antagonists & inhibitors
Membrane Glycoproteins / genetics
Membrane Glycoproteins / metabolism*
Mice
Mice, Inbred C57BL
Mutation
Proteasome Endopeptidase Complex
Protein Stability
RNA Interference
RNA, Small Interfering
Recombinant Proteins / chemistry
Recombinant Proteins / metabolism
Specific Pathogen-Free Organisms
Toll-Like Receptor 7 / agonists
Toll-Like Receptor 7 / antagonists & inhibitors
Toll-Like Receptor 7 / genetics
Toll-Like Receptor 7 / metabolism*
Toll-Like Receptor 9 / agonists
Toll-Like Receptor 9 / antagonists & inhibitors
Toll-Like Receptor 9 / genetics
Toll-Like Receptor 9 / metabolism*
Ubiquitination

Substances

Apoptosis Regulatory Proteins
Interferon Regulatory Factor-7
Interferon Type I
Irf7 protein, mouse
Ligands
Membrane Glycoproteins
RNA, Small Interfering
Recombinant Proteins
TRIM35 protein, mouse
Tlr7 protein, mouse
Tlr9 protein, mouse
Toll-Like Receptor 7
Toll-Like Receptor 9
Proteasome Endopeptidase Complex