Deubiquitination and stabilization of T-bet by USP10

作者：Pan, Lina; Chen, Zuojia; Wang, Linlin; Chen, Chen; Li, Dan; Wan, Huanying; Li, Bin^*; Shi, Guochao

来源：Biochemical and Biophysical Research Communications, 2014, 449(3): 289-294.

DOI：10.1016/j.bbrc.2014.05.037

• T-bet
• USP10
• Deubiquitination
• Quercetin
• Inflammation

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-gamma. 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-gamma to fight against Th2-dominated inflammation.

• 出版日期2014-7-4
• 单位上海市闵行区中心医院; 中国科学院上海巴斯德研究所; 上海交通大学