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C-Terminal Farnesylation of UCH-L1 Plays a Role in Transport of Epstein-Barr Virus Primary Oncoprotein LMP1 to Exosomes.
Article in mSphere. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed.
- Review
- Article
- A State-of-the-Art Review on the Recent Advances in Exosomes in Oncogenic Virus.Health science reports · 2024Article
- Non-functional ubiquitin C-terminal hydrolase L1 drives podocyte injury through impairing proteasomes in autoimmune glomerulonephritis.Nature communications · 2023Article
- Pivotal Role of Ubiquitin Carboxyl-Terminal Hydrolase L1 (UCHL1) in Uterine Leiomyoma.Biomolecules · 2023Article
- Small extracellular vesicles as key players in cancer development caused by human oncogenic viruses.Infectious agents and cancer · 2022Review
- Protein Farnesylation on Nasopharyngeal Carcinoma, Molecular Background and Its Potential as a Therapeutic Target.Cancers · 2022Review
- Integrative biology of extracellular vesicles in diabetes mellitus and diabetic complications.Theranostics · 2022Review
- New insights into Epstein‑Barr virus‑associated tumors: Exosomes (Review).Oncology reports · 2022Review
- New Look of EBV LMP1 Signaling Landscape.Cancers · 2021Review
- Long-term inhibition of UCHL1 decreases hypertension and retinopathy in spontaneously hypertensive rats.The Journal of international medical research · 2021Article
- Signaling pathways of EBV-induced oncogenesis.Cancer cell international · 2021Review
- The Role of Viral Proteins in the Regulation of Exosomes Biogenesis.Frontiers in cellular and infection microbiology · 2021Review
- The role of Exosomes in the Pathogenesis of Nasopharyngeal Carcinoma and the involved Clinical Application.International journal of biological sciences · 2021Review
- Regulation of Deubiquitinating Enzymes by Post-Translational Modifications.International journal of molecular sciences · 2020Review
- The deubiquitinase UCHL1 regulates cardiac hypertrophy by stabilizing epidermal growth factor receptor.Science advances · 2020Article
- Epstein-Barr virus-encoded latent membrane protein 1 promotes extracellular vesicle secretion through syndecan-2 and synaptotagmin-like-4 in nasopharyngeal carcinoma cells.Cancer science · 2020Article
- Extracellular Vesicles in Epstein-Barr Virus Pathogenesis.Current clinical microbiology reports · 2019Article
- Inhibition of UCH-L1 Deubiquitinating Activity with Two Forms of LDN-57444 Has Anti-Invasive Effects in Metastatic Carcinoma Cells.International journal of molecular sciences · 2019Article
- The role of extracellular vesicles from different origin in the microenvironment of head and neck cancers.Molecular cancer · 2019Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Increasing evidence shows that exosomes are key regulators in cancer cell-to-cell communication. Several reports on Epstein-Barr virus (EBV)-related malignancies demonstrate that latent membrane protein 1 (LMP1) secreted by exosomes derived from EBV- or LMP1-positive cells can promote cancer progression and metastasis. However, the mechanism by which LMP1 is loaded into exosomes is still poorly understood. Here, we examined whether the process of LMP1 loading into exosomes is linked to the multifunctional molecule of the ubiquitin system-ubiquitin C-terminal hydrolase-L1 (UCH-L1). For the first time, we demonstrate that LMP1 is physically associated with UCH-L1 and that directing of LMP1 to exosomes is mediated by C-terminal farnesylation of UCH-L1. Additionally, we found that the FTI-277 farnesyltransferase inhibitor reduces motility- and anchorage-independent growth of EBV-positive cells in functional assays. On the basis of our results, we conclude that C-terminal farnesylation of UCH-L1 is one of the key mechanisms by which LMP1 is sorted to exosomes. We hypothesize that inhibition of farnesylation with specific small-molecule inhibitors blocks exosome-mediated transfer of prometastatic molecules such as LMP1 during cancer cell-to-cell communications and thereby impedes the process of cancer invasion.
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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.