USP16-mediated deubiquitination of calcineurin A controls peripheral T cell maintenance

Zhang, Yu; Liu, Rongbei; Cao, Qian; Fan, Ke-qi; Huang, Liying; Yu, Jian-shuai; Gao, Zijun; Huang, Tao; Zhong, Jiang-yan; Mao, Xin-tao; Wang, Fei; Xiao, Peng; Zhao, Yuan; Feng, Xin‐Hua; Li, Yi-yuan; Jin, Jin

doi:10.1172/jci123801

Cited by 41 publications

(40 citation statements)

References 58 publications

(57 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The in vivo ubiquitination assay was performed as previously described ( Liu et al, 2018 ; Zhang et al, 2019 ). In brief, VSV infected or uninfected macrophages or HEK293T cells transfected with the desired plasmids were lysed with cell lysis RIPA buffer (50 mM Tris-HCl, pH 7.4, 150 mM NaCl, 1% NP-40, 0.5% sodium deoxycholate, and 1 mM EDTA) containing protease inhibitor and N -ethylmaleimide (Sigma-Aldrich).…”

Section: Methodsmentioning

confidence: 99%

TRIM24 facilitates antiviral immunity through mediating K63-linked TRAF3 ubiquitination

Zhu

Gan

et al. 2020

Journal of Experimental Medicine

View full text Add to dashboard Cite

Ubiquitination is an essential mechanism in the control of antiviral immunity upon virus infection. Here, we identify a series of ubiquitination-modulating enzymes that are modulated by vesicular stomatitis virus (VSV). Notably, TRIM24 is down-regulated through direct transcriptional suppression induced by VSV-activated IRF3. Reducing or ablating TRIM24 compromises type I IFN (IFN-I) induction upon RNA virus infection and thus renders mice more sensitive to VSV infection. Mechanistically, VSV infection induces abundant TRIM24 translocation to mitochondria, where TRIM24 binds with TRAF3 and directly mediates K63-linked TRAF3 ubiquitination at K429/K436. This modification of TRAF3 enables its association with MAVS and TBK1, which consequently activates downstream antiviral signaling. Together, these findings establish TRIM24 as a critical positive regulator in controlling the activation of antiviral signaling and describe a previously unknown mechanism of TRIM24 function.

show abstract

Section: Methodsmentioning

confidence: 99%

TRIM24 facilitates antiviral immunity through mediating K63-linked TRAF3 ubiquitination

Zhu

Gan

et al. 2020

Journal of Experimental Medicine

View full text Add to dashboard Cite

show abstract

“…Our results demonstrated that the treatment of DOX significantly increased the percentage of CRT positive cells, and the release of extracellular HMGB1 and ATP. Additionally, the release of HMGB1 is a late event of ICD, leading to matured DCs to present tumor-associated antigen to the T cells (Liu et al 2018;Zhang et al 2019). We then co-cultured DOX-treated HCC cells with DCs, and the results demonstrated that higher amount of matured DCs in the DOX-treated treated group as compared with those in the control group.…”

Section: Discussionmentioning

confidence: 94%

Nanomedicine-mediated induction of immunogenic cell death and prevention of PD-L1 overexpression for enhanced hepatocellular carcinoma therapy

et al. 2020

View full text Add to dashboard Cite

Background The present study aims to develop a nanoparticle encapsulating doxorubicin (DOX) and programmed death-ligand 1 (PD-L1) siRNA and evaluate its anti-tumor effects on hepatoma carcinoma (HCC). Methods Nanoparticle encapsulating DOX and PD-L1 siRNA (NPDOX/siPD-L1) was characterized by dynamic light scattering and transmission electron microscopy. Flow cytometry was applied to analyze cell populations, NPDOX/siPD-L1 internalization, and cell apoptosis. Real-Time (RT)-quantitative reverse transcription (qPCR) and western blotting were used to determine the mRNA and protein levels, respectively. Released ATP was determined using ATP determination kit and cytokines were determined using specific ELISAs. A tumor-bearing animal model was established to evaluate the anti-tumor effects of NPDOX/siPD-L1. Results Treatment of NPDOX/siPD-L1 induced immunogenic cell death (ICD) and PD-L1 overexpression in HCC. In vivo study demonstrated that intravenously injection of NPDOX/siPD-L1 significantly inhibited the tumor volume and PD-L1 expressions of tumor tissue in the H22 tumor-bearing animal model. Besides, the treatment of NPDOX/siPD-L1 also regulated the populations of matured dendritic cells and cytotoxic T cells and the productions of cytokines in the tumor tissues. Conclusion Taken together, NPDOX/siPD-L1 showed significant anti-tumor effects on HCC by the induction of ICD and inhibition of PD-L1 overexpression.

show abstract

“…However, children with DS are predisposed to acute lymphoblastic leukemia (ALL), indicating that immune cells are possibly regulated by USP16 [58]. A recent study by Zhang et al demonstrated that expression of USP16 is significantly increased in T cells of patients with autoimmune diseases [59]. Upon intracellular calcium stimulation, the Lys29 polyubiquitination of calcineurin A (CNA) blocks the recruitment of NFAT and this polyubiquitination can be reduced by USP16 (Fig.…”

Section: Usp16mentioning

confidence: 99%

“…Deletion of USP16 increases ubiquitination of CNA and thereby reduces transcription of NFATinduced genes. As a result, both the maintenance and proliferation of T cells are defective in T cell-specific USP16 knockout mice, and these mice are refractory to T cellmediated autoimmune diseases including inflammatory bowel disease and EAE [59]. Specific USP16 inhibitors might be of potential efficacy in treating autoimmune diseases mediated by T cells, such as MS.…”

Section: Usp16mentioning

confidence: 99%

Deubiquitinating enzymes (DUBs): DoUBle-edged swords in CNS autoimmunity

Ruan

Schlüter

Wang

2020

J Neuroinflammation

View full text Add to dashboard Cite

Multiple sclerosis (MS) is the most common autoimmune disease of the CNS. The etiology of MS is still unclear but it is widely recognized that both genetic and environmental factors contribute to its pathogenesis. Immune signaling and responses are critically regulated by ubiquitination, a posttranslational modification that is promoted by ubiquitinating enzymes and inhibited by deubiquitinating enzymes (DUBs). Genome-wide association studies (GWASs) identified that polymorphisms in or in the vicinity of two human DUB genes TNFAIP3 and USP18 were associated with MS susceptibility. Studies with experimental autoimmune encephalomyelitis (EAE), an animal model of MS, have provided biological rationale for the correlation between these DUBs and MS. Additional studies have shown that other DUBs are also involved in EAE by controlling distinct cell populations. Therefore, DUBs are emerging as crucial regulators of MS/EAE and might become potential therapeutic targets for the clinical treatment of MS.

show abstract

USP16-mediated deubiquitination of calcineurin A controls peripheral T cell maintenance

Cited by 41 publications

References 58 publications

TRIM24 facilitates antiviral immunity through mediating K63-linked TRAF3 ubiquitination

TRIM24 facilitates antiviral immunity through mediating K63-linked TRAF3 ubiquitination

Nanomedicine-mediated induction of immunogenic cell death and prevention of PD-L1 overexpression for enhanced hepatocellular carcinoma therapy

Deubiquitinating enzymes (DUBs): DoUBle-edged swords in CNS autoimmunity

Contact Info

Product

Resources

About