IndraLab

Statements

USP18 inhibits ISG15. 11 / 11
| 11
reach
"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)."
31820845
reach
"Immunoprecipitation (IP) assays confirmed that ISG15 directly complexed with PTEN protein and this conjugation was attenuated by engineered overexpression of USP18."
27980214
reach
"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."
29618802
reach
"Consistently, USP18 was able to efficiently reverse the ISG15 modification from ADAMTS1 in a dose-dependent manner (Fig. 5G)."
37170317
reach
"USP18 activity reduces ISG15 protein conjugation and promotes tumorigenesis if an oncogenic substrate is stabilized by USP18."
28242811
reach
"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)."
| DOI
reach
"In contrast, binding this free ISG15, USP18 suppresses JAK-STAT signaling further counteracting IFN signaling.By better understanding the ISG15 pathway, it may be possible to target certain illnesses on a case-by-case basis without the need for general activation of IFN signaling with its hundreds of downstream targets."
35764457
reach
"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."
33203188
reach
"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)."
28165509
reach
"As expected, USP18 silencing dramatically decreased USP18 protein and increased the free ISG15 protein compared to the control group (XREF_FIG)."
27227879
reach
"Finally, USP18 (an ISG15 specific isopeptidase enzyme) can reverse ISG15 conjugation of target proteins."
28186990