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USP22 binds STING1. 16 / 17
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"In line with this, USP22-induced ISG expression could be reversed as well in USP22-STING dKO HT-29 cells (Fig. xref )."
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"Additionally, USP22-mediated increases in IFN-λ expression could also largely be reduced upon USP22-STING dKO, whereas expression of IFN-α and IFN-β remained largely unaffected (Fig. xref )."
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"The differential response to ISD, but not poly(I:C), and the reversal of the IFN signature in USP22-STING dKO hIECs suggests an important role of USP22 in the control of STING-induced type III IFN signaling."
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"E. Western blot 831 analysis of STING and USP22 expression levels in control-NHT, control-USP22 KO 832 #1 and #6, STING-NHT and STING-USP22 KO #1 and #6 double KO (dKO) HT-29 833 cells."
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"To investigate the significance of USP22 and the 326 resulting STING-mediated upregulation of type III IFN and ISG signaling for viral327 defense, the role of the USP22-STING axis was tested during SARSexpression of STING, compared to wild-type (WT) and NHT 332 CRISPR/Cas9 control Caco-2 cells (Figure 6A)."
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"Intriguingly, 351 USP22-STING dKO hIECs exhibit higher SARS-CoV-2 replication rates as well as the formation of more de novo infectious viral particles compared to USP22 inflammatory diseases and cancer 1,2 ."
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"To confirm the role of STING in USP22-induced type III IFN signaling, USP22-STING dKO HT-29 cells were generated (Fig. xref )."
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"USP22-STING dKO cells exhibited strikingly reduced levels of basal and phosphorylated STAT1 protein compared to USP22 KO HT-29 cells (Fig. xref ), suggesting a STING-dependent rescue of the USP22-dependent IFN signature."
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"F. Quantification of relative SARS-CoV-2 835 genome expression of SARS-CoV-2-infected control-NHT, control-USP22 KO #1 and 836 #6, STING-NHT and STING-USP22 KO #1 and #6 dKO HT-29 cells at 24 hpi."
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"In line with this, USP22-283 induced ISG expression could be reversed as well in USP22-STING dKO HT-29 cells 284 (Figure 4H)."
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"To investigate the significance of USP22 and the resulting STING-mediated upregulation of type III IFN and ISG signaling for viral defense, the role of the USP22-STING axis was tested during SARS-CoV-2 infection."
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"Intriguingly, USP22-STING dKO hIECs exhibit higher SARS-CoV-2 replication rates as well as the formation of more de novo infectious viral particles compared to USP22 KO hIECs, confirming that the USP22-STING connection also affects antiviral defense against SARS-CoV-2 infection (Fig. xref and Supplemental Fig. xref C)."
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"Increased STAT1 phosphorylation in USP22 KO Caco-2 cells could be reduced by USP22-STING dKO, confirming a highly conserved role of USP22 in regulating type III IFN via STING (Fig. xref )."
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"To confirm the role of STING in USP22-induced type III IFN 279 signaling, USP22-STING dKO HT-29 cells were generated (Figure 4G)."
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"Accordingly, IFNL1 and ISG mRNA expression was also rescued in USP22-STING dKO Caco-2 cells, compared to USP22 KO, whereas no STING-dependent alterations could be detected in panIFNA and IFNB1 mRNA expression in STING-USP22 dKO Caco-2 cells compared to USP22 KO cells (Fig. xref )."
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"288 289 USP22 negatively regulates STING activation and ubiquitination 290 The differential response to ISD, but not poly(I:C), and the reversal of the IFN signature 291 in USP22-STING dKO hIECs suggests an important role of USP22 in the control of 292 STING-induced type III IFN signaling."
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