The deubiquitinating enzyme USP48 stabilizes TRAF2 and reduces E‐cadherin‐mediated adherens junctions

Li, Shuang; Wang, Dan; Zhao, Jing; Weathington, Nathaniel M.; Shang, Dong; Zhao, Yutong

doi:10.1096/fj.201700415rr

Cited by 29 publications

(28 citation statements)

References 57 publications

(76 reference statements)

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“…Phosphorylation of TRAF2 promotes K63‐linked polyubiquitination . It is also reported that the deubiquitinating enzyme USP48 stabilizes TRAF2 by modifying its ubiquitination .…”

Section: Discussionmentioning

confidence: 95%

Tripartite motif‐containing 37 (TRIM37) promotes the aggressiveness of non‐small‐cell lung cancer cells by activating the NF‐κB pathway

Deng

Zhao

et al. 2018

The Journal of Pathology

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Non-small-cell lung cancer (NSCLC), in which the NF-κB pathway is constitutively activated, is one of the most common malignancies. Herein, we identify an E3 ubiquitin ligase, tripartite motif-containing 37 (TRIM37), participating in the K63 polyubiquitination of TRAF2, which is a significant step in the activation of NF-κB signaling. Both the mRNA and the protein expression levels of TRIM37 were much higher in NSCLC cell lines and tissues than in normal bronchial epithelial cells and matched adjacent non-tumor tissues. TRIM37 expression correlated closely with clinical stage and poor survival in NSCLC. Overexpression of TRIM37 antagonized cisplatin-induced apoptosis, induced angiogenesis and proliferation, and increased the aggressiveness of NSCLC cells in vitro and in vivo, whereas inhibition of TRIM37 led to the opposite effects. Gene set enrichment analysis (GSEA) showed that TRIM37 expression significantly correlated with NF-κB signaling. Furthermore, we found that TRIM37 bound to TRAF2 and promoted K63-linked ubiquitination of TRAF2, sustaining the eventual activation of the NF-κB pathway. Mutation in the ring finger domain of TRIM37, a hallmark of E3 ubiquitin ligases, led to loss of the ability to promote K63 polyubiquitination of TRAF2 and activate NF-κB signaling. Taken together, our findings provide evidence that TRIM37 plays an important role in constitutive NF-κB pathway activation and could serve as a prognostic factor and therapeutic target in NSCLC. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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“…Phosphorylation of TRAF2 promotes K63‐linked polyubiquitination . It is also reported that the deubiquitinating enzyme USP48 stabilizes TRAF2 by modifying its ubiquitination .…”

Section: Discussionmentioning

confidence: 95%

Tripartite motif‐containing 37 (TRIM37) promotes the aggressiveness of non‐small‐cell lung cancer cells by activating the NF‐κB pathway

Deng

Zhao

et al. 2018

The Journal of Pathology

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“…USP48 (also known as USP31) interacted with and deubiquitinated TRAF2 in beas2B cells [71]. A noteworthy fact is that TRAF2 in JNK pathway was targeted by USP48, but not TRAF2 in NF-κB signaling [71].…”

Section: Usp48mentioning

confidence: 99%

“…Exposure to TNFα caused GSK3β-mediated phosphorylation of USP48, leading to deubiquitination of TRAF2 in beas2B cells, increasing JNK signaling upon TNF-α-induction [71].…”

Section: Usp48mentioning

confidence: 99%

Regulatory interplay between deubiquitinating enzymes and cytokines

Woo

Baek

2019

Cytokine & Growth Factor Reviews

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A B S T R A C TDeubiquitinating enzymes (DUBs) are cysteine protease proteins that reverse the ubiquitination by removing ubiquitins from the target protein. With over 100 DUBs identified and categorized into at least 7 families, many DUBs interact with one or more cytokines, influencing cellular processes, such as antiviral responses, inflammatory responses, apoptosis, etc. While some DUBs influence cytokine pathway or production, some DUBs are cytokine-inducible. In this article, we summarize a list of DUBs, their interaction with cytokines, target proteins and mechanisms of action.

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“…Deubiquitination and DUBs have been shown to regulate adherence of junctional proteins [101]. For example, USP48 regulates E-cadherin mRNA levels through stabilizing the TRAF2-JNK pathway in lung epithelial cells [69]. This study exhibits an indirect effect of DUBs on regulation of E-cadherin levels and lung epithelial barrier integrity.…”

Section: Dubsmentioning

confidence: 66%

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 deubiquitinating enzyme USP48 stabilizes TRAF2 and reduces E‐cadherin‐mediated adherens junctions

Cited by 29 publications

References 57 publications

Tripartite motif‐containing 37 (TRIM37) promotes the aggressiveness of non‐small‐cell lung cancer cells by activating the NF‐κB pathway

Tripartite motif‐containing 37 (TRIM37) promotes the aggressiveness of non‐small‐cell lung cancer cells by activating the NF‐κB pathway

Regulatory interplay between deubiquitinating enzymes and cytokines

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

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