ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2018
The deubiquitinating enzyme USP48 stabilizes TRAF2 and reduces E-cadherin-mediated adherens junctions.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 43 citations in OpenAlex.
- Amyloid Precursor Protein Processing Links Female Urgency Urinary Incontinence with Alzheimer's Disease: Implications for Treatment.International journal of molecular sciences · 2026Article
- Caspase 3-specific cleavage of ubiquitin-specific peptidase 48 enhances drug-induced apoptosis in AML.Cancer biology & therapy · 2025Article
- USP33 promotes pulmonary microvascular endothelial cell pyroptosis by stabilizing TRAF2 through deubiquitination.Histology and histopathology · 2025Article
- Inflammation and cancer cell survival: TRAF2 as a key player.Cell death & disease · 2025Review
- GRK2 activates TRAF2-NF-Acta pharmaceutica Sinica. B · 2025Article
- 1'-Acetoxychavicol Acetate Selectively Downregulates Tumor Necrosis Factor Receptor-Associated Factor 2 (TRAF2) Expression.Molecules (Basel, Switzerland) · 2025Article
- CSN-CRL Complexes: New Regulators of Adipogenesis.Biomolecules · 2025Review
- Review
- USP48 deubiquitination stabilizes SLC1A5 to inhibit retinal pigment epithelium cell inflammation, oxidative stress and ferroptosis in the progression of diabetic retinopathy.Journal of bioenergetics and biomembranes · 2024Article
- Friend or foe? Reciprocal regulation between E3 ubiquitin ligases and deubiquitinases.Biochemical Society transactions · 2024Review
- The deubiquitinating enzyme OTUD7b protects dendritic cells from TNF-induced apoptosis by stabilizing the E3 ligase TRAF2.Cell death & disease · 2023Article
- Exploiting E3 ubiquitin ligases to reeducate the tumor microenvironment for cancer therapy.Experimental hematology & oncology · 2023Review
- The Deubiquitinating Enzyme USP48 Interacts with the Retinal Degeneration-Associated Proteins UNC119a and ARL3.International journal of molecular sciences · 2022Article
- Article
- USP48 and A20 synergistically promote cell survival in Helicobacter pylori infection.Cellular and molecular life sciences : CMLS · 2022Article
- Translocating proteins compartment-specifically alter the fate of epithelial-mesenchymal transition in a compartmentalized Boolean network model.NPJ systems biology and applications · 2022Article
- miR-489-3p promotes malignant progression of non-small cell lung cancer through the inactivation of Wnt/β-catenin signaling pathway via regulating USP48.Respiratory research · 2022Article
- SMYD2-mediated TRAF2 methylation promotes the NF-κB signaling pathways in inflammatory diseases.Clinical and translational medicine · 2021Article
- USP48 Governs Cell Cycle Progression by Regulating the Protein Level of Aurora B.International journal of molecular sciences · 2021Article
- IL-37-induced activation of glycogen synthase kinase 3β promotes IL-1R8/Sigirr phosphorylation, internalization, and degradation in lung epithelial cells.Journal of cellular physiology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
The tumor necrosis factor receptor-associated factor 2 (TRAF2) is a second messenger adaptor protein that plays an essential role in propagating TNF-α-mediated signaling pathways. Modulation of TRAF2 activity by ubiquitination is well studied; however, the deubiquitinating enzyme (DUB), which regulates TRAF2 stability, has not been identified. Here we reveal USP48 as the first identified DUB to deubiquitinate and stabilize TRAF2 in epithelial cells. Down-regulation of USP48 increases K48-linked polyubiquitination of TRAF2 and reduces TRAF2 protein levels. Interestingly, USP48 only targets the TRAF2 related to JNK pathway, not the TRAF2 related to NF-κB and p38 pathways. USP48 is serine phosphorylated in response to TNF-α. The phosphorylation is catalyzed by glycogen synthase kinase 3β (GSK3β), ultimately resulting in increases in USP48 DUB activity. Furthermore, we reveal a new biologic function of TRAF2 that contributes to epithelial barrier dysfunction, which is attenuated by knockdown of USP48. Inhibition of TRAF2/JNK pathway increases E (epithelial)-cadherin expression and enhances epithelial barrier integrity, while knockdown of USP48 attenuates TNF-α/JNK pathway and increases E-cadherin expression and cell-cell junction in epithelial cells. These data, taken together, indicate that USP48 stabilizes TRAF2, which is promoted by GSK3β-mediated phosphorylation. Further, down-regulation of USP48 increases E-cadherin expression and epithelial barrier integrity through reducing TRAF2 stability.-Li, S., Wang, D., Zhao, J., Weathington, N. M., Shang, D., Zhao, Y. The deubiquitinating enzyme USP48 stabilizes TRAF2 and reduces E-cadherin-mediated adherens junctions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.