ArticleThe EMBO journal2011
LMP1 association with CD63 in endosomes and secretion via exosomes limits constitutive NF-κB activation.
Article in The EMBO journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers.
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Who cites it
140 citing papers in PubMed, 227 citations in OpenAlex.
- Exosome in Hashimoto's thyroiditis: from pathogenesis to diagnostic and therapeutic potential.Molecular biology reports · 2026Review
- Biology and therapeutic potential of extracellular vesicle targeting and uptake.Nature reviews. Molecular cell biology · 2026Review
- Review
- Heat shock proteins function as signaling molecules to mediate neuron-glia communication in C. elegans during aging.Nature neuroscience · 2025Article
- Extracellular Vesicular Delta-Like Ligand 3 and Subtype Transcription Factors for Small Cell Lung Cancer Diagnosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Roles of extracellular vesicles from mesenchymal stem cells in regeneration.Molecules and cells · 2024Review
- CD63 sorts cholesterol into endosomes for storage and distribution via exosomes.Nature cell biology · 2024Article
- The multifunctionProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Bioengineering extracellular vesicle cargo for optimal therapeutic efficiency.Molecular therapy. Methods & clinical development · 2024Review
- Arf GTPase-Activating proteins ADAP1 and ARAP1 regulate incorporation of CD63 in multivesicular bodies.Biology open · 2024Article
- Extracellular Vesicular Analysis of Glypican 1 mRNA and Protein for Pancreatic Cancer Diagnosis and Prognosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Heat Shock Proteins Function as Signaling Molecules to Mediate Neuron-Glia Communication During Aging.bioRxiv : the preprint server for biology · 2024Article
- Impact of UPF2 on the levels of CD81 on extracellular vesicles.Frontiers in cell and developmental biology · 2024Article
- Exosomes as Powerful Biomarkers in Cancer: Recent Advances in Isolation and Detection Techniques.International journal of nanomedicine · 2024Review
- Article
- Extracellular Vesicles as a Translational Approach for the Treatment of COVID-19 Disease: An Updated Overview.Viruses · 2023Review
- A Review Study of the Participation of Late Domains in Sorting and Transport of Viral Factors to Exosomes.Life (Basel, Switzerland) · 2023Review
- Extracellular Vesicles in Neurodegenerative Diseases: An Update.International journal of molecular sciences · 2023Review
- Exosomal release of the virus-encoded chemokine receptor US28 contributes to chemokine scavenging.iScience · 2023Article
- STIM1-regulated exosomal EBV-LMP1 empowers endothelial cells with an aggressive phenotype by activating the Akt/ERK pathway in nasopharyngeal carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2023Article
80 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
The ubiquitous Epstein Barr virus (EBV) exploits human B-cell development to establish a persistent infection in ∼90% of the world population. Constitutive activation of NF-κB by the viral oncogene latent membrane protein 1 (LMP1) has an important role in persistence, but is a risk factor for EBV-associated lymphomas. Here, we demonstrate that endogenous LMP1 escapes degradation upon accumulation within intraluminal vesicles of multivesicular endosomes and secretion via exosomes. LMP1 associates and traffics with the intracellular tetraspanin CD63 into vesicles that lack MHC II and sustain low cholesterol levels, even in 'cholesterol-trapping' conditions. The lipid-raft anchoring sequence FWLY, nor ubiquitylation of the N-terminus, controls LMP1 sorting into exosomes. Rather, C-terminal modifications that retain LMP1 in Golgi compartments preclude assembly within CD63-enriched domains and/or exosomal discharge leading to NF-κB overstimulation. Interference through shRNAs further proved the antagonizing role of CD63 in LMP1-mediated signalling. Thus, LMP1 exploits CD63-enriched microdomains to restrain downstream NF-κB activation by promoting trafficking in the endosomal-exosomal pathway. CD63 is thus a critical mediator of LMP1 function in- and outside-infected (tumour) cells.
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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.