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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-β 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-β 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.
This article was published in the following journal.
Name: Molecular immunology
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The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activa
An Ig domain-containing membrane receptor that is expressed by TH1 CELLS. It regulates the activation of MACROPHAGES and inhibits TH1-mediated auto- and alloimmune responses to promote IMMUNE TOLERANCE.
A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).
A caspase-like cysteine endopeptidase that also exhibits ubiquitin ligase activity. It contains an N-terminal DEATH DOMAIN, two IMMUNOGLOBULIN-LIKE DOMAINS, and localizes to the perinuclear region of MONOCYTES, where it functions in activation of NF-KAPPA B; it also binds to and activates TRAF6. Chromosomal translocations involving the MALT1 and BIRC2 genes are associated with MALT LYMPHOMA, and mutations in the MALT1 gene are associated with Type 12 IMMUNODEFICIENCY SYNDROMES.
This enzyme is a lymphoid-specific src family tyrosine kinase that is critical for T-cell development and activation. Lck is associated with the cytoplasmic domains of CD4, CD8 and the beta-chain of the IL-2 receptor, and is thought to be involved in the earliest steps of TCR-mediated T-cell activation.
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