Deubiquitination and stabilization of T-bet by USP10

Biochem Biophys Res Commun. 2014 Jul 4;449(3):289-94. doi: 10.1016/j.bbrc.2014.05.037. Epub 2014 May 17.

Abstract

The T-box transcriptional factor T-bet is crucial in the development, differentiation and function of Th1 cells. It drives Th1 immune response primarily through promoting expression of Th1 hallmark cytokine IFN-γ. Although T-bet was found associated with many immune-mediated diseases such as asthma and systemic sclerosis, little is known about the regulation of T-bet stability and function. Here we identified USP10, a carboxyl-terminal ubiquitin-processing protease, could interact with T-bet in the nucleus. Overexpression of USP10 directly inhibited T-bet ubiquitination and increased the expression of T-bet. We further confirmed Quercetin, a reported inhibitor of T-bet, could target USP10. Quercetin treatment downregulated USP10 and promoted T-bet degradation in a proteasome dependent way. Moreover, we found USP10 expression was upregulated in asthmatic patient PBMC, suggesting USP10 may maintain high level of T-bet and IFN-γ to fight against Th2-dominated inflammation.

Keywords: Deubiquitination; Inflammation; Quercetin; T-bet; USP10.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asthma / immunology
  • Cell Nucleus / metabolism
  • Down-Regulation
  • HEK293 Cells
  • Humans
  • Inflammation
  • Protein Stability
  • Proteolysis
  • Quercetin / pharmacology
  • T-Box Domain Proteins / antagonists & inhibitors
  • T-Box Domain Proteins / metabolism*
  • Th1 Cells / immunology
  • Ubiquitin Thiolesterase / antagonists & inhibitors
  • Ubiquitin Thiolesterase / metabolism*
  • Ubiquitination / drug effects
  • Ubiquitination / physiology*

Substances

  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • USP10 protein, human
  • Quercetin
  • Ubiquitin Thiolesterase