2. Academic Validation
  3. Ubiquitin specific protease 5 negatively regulates the IFNs-mediated antiviral activity via targeting SMURF1

Ubiquitin specific protease 5 negatively regulates the IFNs-mediated antiviral activity via targeting SMURF1

  • Int Immunopharmacol. 2020 Oct;87:106763. doi: 10.1016/j.intimp.2020.106763.
Guanghui Qian 1,  Liyan Zhu 2,  Chengcheng Huang 1,  Ying Liu 1,  Ying Ren 2,  Yueyue Ding 1,  Weiguo Qian 1,  Qiuqin Xu 1,  Hui Zheng 3,  Haitao Lv 4
Affiliations

Affiliations

  • 1 Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu Province 215025, China.
  • 2 Medical College of Soochow University, Suzhou 215123, China.
  • 3 Medical College of Soochow University, Suzhou 215123, China. Electronic address: huizheng@suda.edu.cn.
  • 4 Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu Province 215025, China. Electronic address: haitaosz@163.com.
PMID: 32683298 DOI: 10.1016/j.intimp.2020.106763
Abstract

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.

Keywords

IFNs; SMURF1; USP5; Ubiquitination; Vesicular stomatitis virus (VSV).

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