TRIM35 negatively regulates TLR7- and TLR9-mediated type I interferon production by targeting IRF7.
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.
Mesh Terms:
Animals, Apoptosis Regulatory Proteins, Cell Line, Cells, Cultured, Dendritic Cells, Down-Regulation, Humans, Interferon Regulatory Factor-7, Interferon Type I, Ligands, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Mutation, Proteasome Endopeptidase Complex, Protein Stability, RNA Interference, RNA, Small Interfering, Recombinant Proteins, Specific Pathogen-Free Organisms, Toll-Like Receptor 7, Toll-Like Receptor 9, Ubiquitination
Animals, Apoptosis Regulatory Proteins, Cell Line, Cells, Cultured, Dendritic Cells, Down-Regulation, Humans, Interferon Regulatory Factor-7, Interferon Type I, Ligands, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Mutation, Proteasome Endopeptidase Complex, Protein Stability, RNA Interference, RNA, Small Interfering, Recombinant Proteins, Specific Pathogen-Free Organisms, Toll-Like Receptor 7, Toll-Like Receptor 9, Ubiquitination
FEBS Lett.
Date: May. 22, 2015
PubMed ID: 25907537
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