Ubiquitin specific protease 5 negatively regulates the IFNs-mediated antiviral activity via targeting SMURF1.
Type I interferons are broadly used for antiviral therapy in clinical. However, the IFNs-mediated antiviral efficacy is commonly restricted by negative regulators. Here, we show that the ubiquitin-specific protease 5 (USP5) inhibits the IFNs-induced p-STAT1 activation (phosphorylation at tyrosine site of STAT1) and its downstream antiviral genes expression. We clarify that USP5 physically interacts with SMURF1 (Smad ubiquitination regulating factor 1) and IFNs signaling regulates the interaction and turnover of both proteins. USP5 enhances the stability and turnover of SMURF1 via decreasing its polyubiquitin expression level, which caused STAT1 to decrease. Importantly, USP5 is also involved in the SMURF1-mediated antiviral response, and its small-molecule inhibitor PYR41 remarkably enhances the IFNs antiviral efficacy. These findings reveal a previously unrecognized function of the USP5 and USP5-SMURF1 axis in regulating the IFNs-mediated antiviral activity.
['Qian|Guanghui|G|', 'Zhu|Liyan|L|', 'Huang|Chengcheng|C|', 'Liu|Ying|Y|', 'Ren|Ying|Y|', 'Ding|Yueyue|Y|', 'Qian|Weiguo|W|', 'Xu|Qiuqin|Q|', 'Zheng|Hui|H|', 'Lv|Haitao|H|']
D000818:Animals D010450:Endopeptidases D057809:HEK293 Cells D006367:HeLa Cells D006801:Humans D016898:Interferon-alpha D051379:Mice D000067996:RAW 264.7 Cells D050794:STAT1 Transcription Factor D044767:Ubiquitin-Protein Ligases D054875:Ubiquitination D018116:Vesiculovirus
Ubiquitination SMURF1 USP5 IFNs Vesicular stomatitis virus (VSV)