The deubiquitinase Otub1 controls the activation of CD8+ T cells and NK cells by regulating IL-15-mediated priming

Zhou, Xiaofei; Yu, Jiayi; Cheng, Xuhong; Zhao, Baoyu; Manyam, Ganiraju C.; Zhang, Li; Schluns, Kimberly S.; Li, Pingwei; Wang, Jing; Sun, Shao‐Cong

doi:10.1038/s41590-019-0405-2

Cited by 76 publications

(88 citation statements)

References 53 publications

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“…OTUB1 regulated the anergy of T-cells via interaction with RNF128/GRAIL ( Lin et al, 2009 ; Stempin et al, 2017 ) and modified the activation of CD8 T cells. As a checkpoint of IL-15-mediated priming, OTUB1 exerts a dramatic influence on the activation of CD8 T cells and NK cells ( Zhou et al, 2019 ). The deficiency of OTUB1 could enhance the sensitization of CD8 T cells to TCR-CD28 and subsequently activate T cells into antigen-specific effector cells ( Zhou et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

“…As a checkpoint of IL-15-mediated priming, OTUB1 exerts a dramatic influence on the activation of CD8 T cells and NK cells ( Zhou et al, 2019 ). The deficiency of OTUB1 could enhance the sensitization of CD8 T cells to TCR-CD28 and subsequently activate T cells into antigen-specific effector cells ( Zhou et al, 2019 ). OTUB1 also potently regulates the function of DC and influences the synthesis of immune factors.…”

Section: Discussionmentioning

confidence: 99%

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OTUB1 Recruits Tumor Infiltrating Lymphocytes and Is a Prognostic Marker in Digestive Cancers

Zhang

Qiu

2020

Front. Mol. Biosci.

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Background: The deubiquitinating enzyme (DUB) OTUB1 can regulate the process of ubiquitination, but the influence of OTUB1 on immunity, apoptosis, autophagy, and the prognosis of digestive cancers requires further exploration. Methods: OTUB1 expression was analyzed with the Oncomine and TIMER database. Kaplan-Meier plotter was used to calculate the association between OTUB1 and clinical prognosis. The regulation of OTUB1 on cancer immunocyte infiltration was determined by the TIMER database. The interaction between OTUB1 and immune genes, gene expression profiling (GEP), key genes of apoptosis and autophagy were analyzed via GEPIA. Protein-protein interaction (PPI), gene expression profiling (GEP), and functional pathway enrichment were also performed with the STRING and Pathway Common databases, respectively. Results: High OTUB1 expression was found in CHOL, LIHC, READ, ESCA, and COAD, which was significantly associated with the poorer OS of LIHC (HR = 2.07, 95% CI = 1.30-3.30, P = 0.002), with modifications by sex, stage, grade, and mutant burden. OTUB1 can promote the recruitment of B cells, CD8 + T cells, macrophages in ESCA, B cells, and neutrophils in LIHC. We determined a significant interaction between OTUB1 and USP8, RNF128, LRIG1, UBB, UBC, STAM2, RNF41, EGFR, RPS27A, and HGS by PPI. This functional pathway indicates the regulatory role of OTUB1on immune, apoptosis, and autophagy through its interaction with TP53 and ATG. Conclusions: OTUB1 performed as a molecular indicator of poor prognosis in digestive cancers, regulated the infiltration of tumor immunocytes, and exerted a significant influence on apoptosis and autophagy. OTUB1 is a potential antitumor target for digestive tumors.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

OTUB1 Recruits Tumor Infiltrating Lymphocytes and Is a Prognostic Marker in Digestive Cancers

Zhang

Qiu

2020

Front. Mol. Biosci.

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“…Given that OTUB1 is versatile in regulating key molecules involved in various cellular activities, it is not surprising that global OTUB1 knockout mice are embryonic lethal [94,95]. A study by Zhou et al shows that OTUB1 inhibits the activation of T cells and NK cells by dampening IL-15R signaling [96]. Given that T cells and NK cells are key mediators in MS [97], OTUB1 might influence EAE by regulating the functions of T cells and NK cells.…”

Section: Otub1mentioning

confidence: 99%

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

Ruan

Schlüter

Wang

2020

J Neuroinflammation

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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.

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“…OTUB1 recruits phosphorylated SMAD2/3 and inhibits its ubiquitination by binding with E2 Ub-conjugating enzyme to enhance TGF-β signaling [80]. OTUB1 regulates the maturation and activation of NK and CD8+T cells via inhibiting AKT ubiquitination [77]. Furthermore, virus-induced OTUB1 degradation blocks the RIG-I-dependent immune signaling cascade and antiviral response [79].…”

Section: Otusmentioning

confidence: 99%

The Role of Deubiquitinating Enzymes in Acute Lung Injury and Acute Respiratory Distress Syndrome

Zou

2020

IJMS

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Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) are characterized by an inflammatory response, alveolar edema, and hypoxemia. ARDS occurs most often in the settings of pneumonia, sepsis, aspiration of gastric contents, or severe trauma. The prevalence of ARDS is approximately 10% in patients of intensive care. There is no effective remedy with mortality high at 30–40%. Most functional proteins are dynamic and stringently governed by ubiquitin proteasomal degradation. Protein ubiquitination is reversible, the covalently attached monoubiquitin or polyubiquitin moieties within the targeted protein can be removed by a group of enzymes called deubiquitinating enzymes (DUBs). Deubiquitination plays an important role in the pathobiology of ALI/ARDS as it regulates proteins critical in engagement of the alveolo-capillary barrier and in the inflammatory response. In this review, we provide an overview of how DUBs emerge in pathogen-induced pulmonary inflammation and related aspects in ALI/ARDS. Better understanding of deubiquitination-relatedsignaling may lead to novel therapeutic approaches by targeting specific elements of the deubiquitination pathways.

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The deubiquitinase Otub1 controls the activation of CD8+ T cells and NK cells by regulating IL-15-mediated priming

Cited by 76 publications

References 53 publications

OTUB1 Recruits Tumor Infiltrating Lymphocytes and Is a Prognostic Marker in Digestive Cancers

OTUB1 Recruits Tumor Infiltrating Lymphocytes and Is a Prognostic Marker in Digestive Cancers

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

The Role of Deubiquitinating Enzymes in Acute Lung Injury and Acute Respiratory Distress Syndrome

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