IndraLab

Statements


| 18

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"We further investigated the effect of USP25 knockdown on virus triggered IFN signaling."

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"Collectively, these findings suggest that USP25 inhibits RIG-I and MDA5-dependent type I IFN signaling."

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"However, the catalytic mutants (C178A and H607A) devoid of DUB activity lost the ability of USP25 WT-mediated IFN inhibition to some degree, indicating that DUB activity is involved in USP25 inhibition of type I IFN induction.Sequence for siRNAs of human USP25."

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"doi: 10.1371/journal.pone.0080976.g005 USP25 Negatively Regulates Type I IFN Signaling PLOS ONE | www.plosone.org 7B), TRAF2 (Figure 7D), and TRAF6 (The deubiquitinating activity of USP25 is involved in virus-induced type I IFN signaling."

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"*P < 0.05 for all pairwise comparisons by one-way ANOVA followed by Dunnett's multiple comparisons test.doi: 10.1371/journal.pone.0080976.g006 USP25 Negatively Regulates Type I IFN Signaling PLOS ONE | www.plosone.orgUSP25 deubiquitinates RIG-I, TRAF2 and TRAF6."

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"To further determine the levels at which USP25 negatively regulates type I IFN signaling, HEK-293T cells were transfected with DNA constructs encoding RIG-I, IPS-1, TRAF2, or TRAF6, together with IFN-beta-Luc."

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"To examine whether the inhibitory effects of USP25 on SEV induced type I IFN signaling is due to its deubiquitinase activity, wild-type USP25 (USP25-WT) and its mutants (C178A and H607A) lacking DUB activity were co-transfected with the promoter luciferase reporter plasmid of IFN-beta, IRF3, NF-kappaB and ISRE, and the luciferase activity was detected."

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"In addition, USP25 deficiency inhibits transcriptional activity of interferon regulatory factor, thereby reducing type I interferon production."
| PMC

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"However, the catalytic mutants (C178A and H607A) devoid of DUB activity lost the ability of USP25 WT-mediated IFN inhibition to some degree, indicating that DUB activity is involved in USP25 inhibition of type I IFN induction.To further determine the levels at which USP25 negatively regulates type I IFN signaling, HEK-293T cells were transfected with DNA constructs encoding RIG-I, IPS-1, TRAF2, or TRAF6, together with IFN-β-Luc."

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"Several studies showed that USP25 negatively regulates virus-induced type I IFN signaling by stabilizing TRAF2, TRAF3 and TRAF6 [64,65,75,87,121,122,123,124]."

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"However, the catalytic mutants (C178A and H607A) devoid of DUB activity lost the ability of USP25 WT mediated IFN inhibition to some degree, indicating that DUB activity is involved in USP25 inhibition of type I IFN induction."

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"In addition, the catalytic USP25 mutants (C178A and H607A) devoid of DUB activity significantly lost the ability of USP25 WT mediated IFN inhibition."

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"To examine whether the inhibitory effects of USP25 on SEV-induced type I IFN signaling is due to its deubiquitinase activity, wild-type USP25 (USP25-WT) and its mutants (C178A and H607A) lacking DUB activity were co-transfected with the promoter luciferase reporter plasmid of IFN-β, IRF3, NF-κB and ISRE, and the luciferase activity was detected."

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"USP25 inhibits SEV induced type I IFN signaling by disrupting activation of IRF3 and NF-kappaB."

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"The input tagged proteins were verified with the indicated antibodies.doi: 10.1371/journal.pone.0080976.g002 USP25 Negatively Regulates Type I IFN Signaling PLOS ONE | www.plosone.orgdoi: 10.1371/journal.pone.0080976.g003 USP25 Negatively Regulates Type I IFN Signaling PLOS ONE | www.plosone.org manner."

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"Interestingly, the genetic deletion of USP21 in macrophages enhances IRF3 activation, IFN production, and antiviral response."

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"Future investigation will be required to test whether these domains of USP25 are also involved in USP25 mediated IFN inhibition."

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"Usp25 deficiency in macrophages enhances TBK1-NF-κB signaling and the induction of inflammatory chemokines and type I interferon-related genes exacerbates pancreatic and lung injury in AP."