IndraLab

Statements

USP18 inhibits ISG15. 11 / 11
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"Finally, USP18 (an ISG15 specific isopeptidase enzyme) can reverse ISG15 conjugation of target proteins."
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"USP18 is the main ISG15 isopeptidase and can inhibit 593 ISG15-mediated ISGylation and can repress the establishment of an antiviral state (Honke et al., 594 2016; Ketscher et al., 2015)."
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"Immunoprecipitation (IP) assays confirmed that ISG15 directly complexed with PTEN protein and this conjugation was attenuated by engineered overexpression of USP18."
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"In particular, replacement of the Ala138 in USP18 by a polar residue in other USPs might block the access of the bulky and hydrophobic Trp121 side chain of ISG15 (XREF_FIG)."
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"As expected, USP18 silencing dramatically decreased USP18 protein and increased the free ISG15 protein compared to the control group (XREF_FIG)."
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"Here, a clear negative feedback loop can be observed, in which Ubiquitin like protein ISG15 (G1P2) induces IFN-gamma expression while Ubl carboxyl-terminal hydrolase 18 (USP18) inhibits G1P2 activity, explaining the observed down-regulation state of IFN-gamma."
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"In particular, replacement of the Ala138 in USP18 by a polar residue in other USPs might block the access of the bulky and hydrophobic Trp121 side chain of ISG15 (Fig. 4d)."
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"ISG15 conjugation (ISGylation) can be reversed by the IFN-a/b-induced isopeptidase (USP18) that cleaves ISG15 from target proteins 4 ."
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"USP18 activity reduces ISG15 protein conjugation and promotes tumorigenesis if an oncogenic substrate is stabilized by USP18."
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"Inhibiting USP18, the negative regulator of ISGylation, has been shown in both cell line and invivo systems to enhance ISG15 conjugation (Ketscher et al., 2015)."
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"In a positive feedback loop, the ISG15 conjugation system is also upregulated by p53 ISGylation to further potentiate p53 transactivity and downregulated by USP18 mediated deISGylation of p53."
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