The Type I Interferon-IRF7 Axis Mediates Transcriptional Expression of Usp25 Gene

J Biol Chem. 2016 Jun 17;291(25):13206-15. doi: 10.1074/jbc.M116.718080. Epub 2016 Apr 27.


Viral infection or lipopolysaccharide (LPS) treatment induces expression of a large array of genes, the products of which play a critical role in host antipathogen immunity and inflammation. We have previously reported that the expression of ubiquitin-specific protease 25 (USP25) is significantly up-regulated after viral infection or LPS treatment, and this is essential for innate immune signaling. However, the mechanism behind this phenomenon is unclear. In this study, we found that viral infection-induced up-regulation of Usp25 is diminished in cells lacking interferon regulatory factor 7 (IRF7) or interferon α receptor 1 (IFNAR1) but not p65. Sendai virus- or type I interferon-induced up-regulation of Usp25 requires de novo protein synthesis of IRF7. Furthermore, IRF7 directly binds to the two conserved IRF binding sites on the USP25 promoter to drive transcription of Usp25, and mutation of these two sites abolished Sendai virus-induced IRF7-mediated activation of the USP25 promoter. Our study has uncovered a previously unknown mechanism by which viral infection or LPS induces up-regulation of USP25.

Keywords: USP25; cell signaling; gene regulation; immunology; interferon; interferon regulatory factor (IRF); transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Enzyme Induction / immunology
  • Herpes Simplex / enzymology
  • Herpesvirus 1, Human / physiology
  • Interferon Regulatory Factor-7 / physiology*
  • Interferon Type I / physiology*
  • Lipopolysaccharides / pharmacology
  • Mice, Knockout
  • Promoter Regions, Genetic
  • Protein Binding
  • Signal Transduction
  • Transcription, Genetic
  • Ubiquitin Thiolesterase / genetics*
  • Ubiquitin Thiolesterase / metabolism
  • Up-Regulation / immunology


  • Interferon Regulatory Factor-7
  • Interferon Type I
  • Irf7 protein, mouse
  • Lipopolysaccharides
  • USP25 protein, mouse
  • Ubiquitin Thiolesterase