IndraLab

Statements

USP18 binds IFNAR1. 6 / 6
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"Their study showed that USP18 does not interact with IFNAR1, but with Box1-Box2 region of IFNAR2 to disrupt its interaction with JAK to inhibit JAK’s tyrosine kinase activity in a DUB activity independent manner [ xref ]."
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"USP18 specifically binds to the intracellular domain of the type I interferon receptor 2 (IFNAR2), interfering with the JAK1-receptor interaction and thereby preventing the downstream phosphorylation cascade and the expression of IFN-stimulated genes (ISGs)."
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"USP18 binds to the Type I interferon receptor and blocks JAK1 activation of interferon signaling, which could also explain the reduction in ISGylation [ xref ]."
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"Usp18 can directly activate the JAK/STAT signaling pathway to promote IFN responses [ xref ] or may bind to interferon receptor 2 (IFNAR2) and inhibit the JAK/STAT [ xref ]."
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"In addition to the enzymatic activity, USP18 also interacts with the type I interferon receptor and shuts off downstream signaling."
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"Interestingly, USP18 in humans (but not in mice) can also interfere with the anti-viral outcome of IFN signaling by an additional mechanism: USP18 can bind the interferon receptor 2 (IFNAR2), block the association of JAK, and possibly limit IFNAR2-IFNAR1 dimerization, thereby interfering with the JAK-STAT signaling pathway xref ."
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