IndraLab

Statements

USP18 inhibits STAT1. 11 / 13
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"XREF_BIBR, XREF_BIBR To asses whether STAT1 or STAT2, which are both upregulated by USP18 inhibition (XREF_FIG), are implicated in the upregulation of Bim, DP5 and PUMA mRNA expression in USP18 silenced cells, we inhibited in parallel USP18 and STAT1 or STAT2 in INS-1E cells by use of specific siRNAs."
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"Interestingly, IL-17A pretreatment increased the expression of suppressor of cytokine signaling (SOCS) 1, SOCS3 and USP18, which were also the ISGs negatively regulating activity of ISGF3."
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"Interferon genes including Interferon (IFN)-induced protein 44-like ( IFI44L ), Interferon-induced protein with tetratricopeptide repeats 1 ( IFIT1 ), Interferon-induced protein with tetratricopeptide[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"We further found that microglial Usp18 negatively regulates the activation of Stat1 and concomitant induction of interferon induced genes, thereby terminating IFN signaling."
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"Silencing USP18 prolongs the phosphorylated state of signal transducer and activator of transcription 1 (STAT1) and enhances the expression of ISGs in response to IFN-alpha [XREF_BIBR]."
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"In mice, Usp18 negatively regulates Stat1 activation and the downstream IFN-I response by interaction with Ifnar2, and mice lacking Usp18 in microglia display brain disease due to uncontrolled IFN-I signalling [6]."
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"In addition, USP18, which is increased by interferon signaling and is stabilized through a noncovalent association with ISG15, also acts to inhibit STAT1 activation by type I interferons to limit undue interferon signaling (17, 18)."
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"Silencing of USP18 by specific siRNA attenuated the pSTAT1 suppression by Ach."
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"USP18 negatively regulates the activation of STAT1 upon interaction with IFNAR2 (Malakhova et al., 2006)."
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"Therefore, knockdown USP18 leads to prolonged and enhanced the activity of STAT1, and upregulated expression of many ISGs."
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"Of note, USP18 knockdown did not increase pSTAT1 in response to IFN-alpha before 24 h; these findings are consistent with previous observations."
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