Deubiquitination and stabilization of T-bet by USP10.
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.
Department of Pulmonary Medicine, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, PR China.
Lina
L
Pan
Key Laboratory of Molecular Virology and Immunology, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (CAS), Shanghai 200031, PR China.
Zuojia
Z
Chen
Department of Pulmonary Medicine, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, PR China.
Linlin
L
Wang
Key Laboratory of Molecular Virology and Immunology, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (CAS), Shanghai 200031, PR China.
Chen
C
Chen
Key Laboratory of Molecular Virology and Immunology, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (CAS), Shanghai 200031, PR China.
Dan
D
Li
Department of Pulmonary Medicine, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, PR China.
Huanying
H
Wan
Key Laboratory of Molecular Virology and Immunology, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (CAS), Shanghai 200031, PR China. Electronic address: binli@sibs.ac.cn.
Bin
B
Li
Department of Pulmonary Medicine, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, PR China. Electronic address: shiguochao@hotmail.com.
Guochao
G
Shi
D001249:Asthma / Q000276:immunology; D002467:Cell Nucleus / Q000378:metabolism; D015536:Down-Regulation; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation; D055550:Protein Stability; D059748:Proteolysis; D011794:Quercetin / Q000494:pharmacology; D020825:T-Box Domain Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology; D043222:Ubiquitin Thiolesterase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054875:Ubiquitination / Q000187:drug effects / Q000502:physiology*; D000098815:T-bet Transcription Factor
D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; C431363:USP10 protein, human; D011794:Quercetin; D043222:Ubiquitin Thiolesterase
Deubiquitination; Inflammation; Quercetin; T-bet; USP10