Roles of ubiquitin-specific proteases in inflammatory diseases

Front Immunol. 2024 Jan 23:15:1258740. doi: 10.3389/fimmu.2024.1258740. eCollection 2024.


Ubiquitin-specific proteases (USPs), as one of the deubiquitinating enzymes (DUBs) families, regulate the fate of proteins and signaling pathway transduction by removing ubiquitin chains from the target proteins. USPs are essential for the modulation of a variety of physiological processes, such as DNA repair, cell metabolism and differentiation, epigenetic modulations as well as protein stability. Recently, extensive research has demonstrated that USPs exert a significant impact on innate and adaptive immune reactions, metabolic syndromes, inflammatory disorders, and infection via post-translational modification processes. This review summarizes the important roles of the USPs in the onset and progression of inflammatory diseases, including periodontitis, pneumonia, atherosclerosis, inflammatory bowel disease, sepsis, hepatitis, diabetes, and obesity. Moreover, we highlight a comprehensive overview of the pathogenesis of USPs in these inflammatory diseases as well as post-translational modifications in the inflammatory responses and pave the way for future prospect of targeted therapies in these inflammatory diseases.

Keywords: deubiquitination; inflammatory diseases; protein stability; targeted therapies; ubiquitin-specific proteases.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation
  • DNA Repair
  • Humans
  • Protein Processing, Post-Translational
  • Ubiquitin* / metabolism
  • Ubiquitin-Specific Proteases*


  • Ubiquitin-Specific Proteases
  • Ubiquitin

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants from National Natural Science Foundation of China (82101012, 82104069, 22172120); Sichuan Science and Technology Program (2021JDRC0158, 2022089); Southwest Jiaotong University Fundamental Research Cultivation Support Program for Medicine-Engineering Integration (2682023ZTPY046); Medical Youth Innovation Project of Sichuan Province (Q20019).