IndraLab

Statements


USP18 activates ISG15. 11 / 11
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"However divergent, ISG15 removal is nevertheless exclusively mediated by USP18 in humans, mice, and zebrafish."

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"In addition, absence of USP18, which cleaves ISG15 from its target protein, prolongs ISG15 mediated ISGylation."

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"USP18 can increase HBV susceptibility by removing isopeptidase activity of ISG15 and promoting HBV replication by downregulating the I-IFN signal transduction pathway."

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"At later stages, USP18 mediated de-ISGylation releases free ISG15, which in turn stabilizes USP18 and tunes down IFN-alpha and beta signalling and inflammation."

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"The absence of USP18 strengthens the signaling of IFN-I and IFN-III; 1,2 and is associated with prolonged Janusactivated kinase/signal transducer and activator of In addition, absence of USP18, which cleaves ISG15 from its target protein, prolongs ISG15-mediated ISGylation."

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"Further investigation with the KEGG pathway enrichment analysis showed those up-regulated genes could cause the activation of the IFN-induced pathway, type II interferon signaling pathway, and regulation of protein ISGylation by the ISG15 deconjugating enzyme USP18 pathway (Figure 4B)."

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"Interestingly, this enhanced type I interferon signalling has not been observed in mice (Box 1), raising interesting questions about the divergent function of ISG15 between species.The regulation of interferon signalling by ISG15 and USP18 also contributes to the unexpected proviral activity for ISG15 that has been associated with chronic viral hepatitis."

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"Our data are consistent with this mechanism, since the blunting of hepatocyte IFN signaling after exposure to inflammatory stimuli is independent of USP18 mediated removal of ISG15 from its target proteins."

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"Usp18 deficient cells have enhanced IFN-alpha and beta signaling and more ISG15 modified proteins."

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"Unlike Lbpro, USP18-mediated ISG15 cleavage leads to ISG15 recycling since USP18 cleaves the isopeptide linkage after the C-terminal GlyGly motif and ISG15 remains competent for reconjugation."

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"Selective inactivation of USP18 isopeptidase activity in vivo enhances ISG15 conjugation and viral resistance."