TARBP2 inhibits IRF7 activation by suppressing TRAF6-mediated K63-linked ubiquitination of IRF7.

Interferon regulatory factor 7 (IRF7), a crucial regulator of type I interferons (IFNs), plays a crucial role in resistance to viral infection. The abnormal production of type I IFNs is associated with many types of disease, such as cancer and inflammatory disorders. Thus, understanding the post-translational modifications of IRF7 is ...
essential to promoting an appropriate immune response. We have recently showed that the TAR RNA binding protein 2 (TARBP2) suppresses IFN-? production and the innate antiviral response by targeting MAVS. Here, we further identified TARBP2 as a novel inhibitor of IRF7, which inhibits IRF7-mediated IFN-? production triggered by the Sendai virus in 293?T cells. Overexpression of TARBP2 inhibits the phosphorylation as well as the K63-linked ubiquitination of IRF7, whilst TARBP2 also impairs the stability of endogenous TRAF6. Furthermore, TARBP2 participates in the interaction between IRF7 and TRAF6, thereby suppressing TRAF6-mediated K63-linked ubiquitination of IRF7, which is a prerequisite of IRF7 phosphorylation. Our findings further reveal the mechanism by which TARBP2 regulates the antiviral signaling pathways of the innate immune system.
Mesh Terms:
HEK293 Cells, Humans, Interferon Regulatory Factor-7, Interferon-beta, Lysine, Phosphorylation, Protein Binding, Proteolysis, RNA-Binding Proteins, Sendai virus, Signal Transduction, TNF Receptor-Associated Factor 6, Ubiquitination
Mol. Immunol.
Date: Dec. 01, 2018
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