ArticlePLoS pathogens2015
TRAF1 Coordinates Polyubiquitin Signaling to Enhance Epstein-Barr Virus LMP1-Mediated Growth and Survival Pathway Activation.
Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 83 citations in OpenAlex.
- Epstein-Barr virus (EBV) infection causes human germinal center B cell-derived lymphomas in the absence of EBNA2 expression.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- EBV (LMP1) enhances cisplatin resistance by enhancing degradation of interferon regulatory factor 3.Cell communication and signaling : CCS · 2026Article
- CRISPR Screens Reveal Epstein-Barr Virus-activated JunB as a Key Lymphoblastoid B cell Dependency Factor that Represses Cyclin Dependent Kinase Inhibitor P18INK4c.bioRxiv : the preprint server for biology · 2026Article
- A CRISPR-Cas9 screen Reveals STEEP1 as a Key Host Dependency Factor for Epstein-Barr Virus Latent Membrane Protein 1 Trafficking and Signaling.bioRxiv : the preprint server for biology · 2026Article
- Epstein-barr virus latent membrane protein 1 targets cIAP1, cIAP2 and TRAF2 for proteasomal degradation to activate the non-canonical NF-κB pathway.PLoS pathogens · 2026Article
- Epstein-Barr Virus Encoded lncRNAs Control the Viral Lytic Switch.bioRxiv : the preprint server for biology · 2025Article
- Epstein-Barr Virus Latent Membrane Protein 1 targets cIAP1, cIAP2 and TRAF2 for Proteasomal Degradation to Activate the Non-canonical NF-κB Pathway.bioRxiv : the preprint server for biology · 2025Article
- Linear ubiquitination mediates coronavirus NSP14-induced NF-κB activation.Cell communication and signaling : CCS · 2024Article
- Review
- The nucleic acid binding protein SFPQ represses EBV lytic reactivation by promoting histone H1 expression.Nature communications · 2024Article
- TRAF1 from a Structural Perspective.Biomolecules · 2024Review
- The microbiota and renal cell carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Germinal center cytokine driven epigenetic control of Epstein-Barr virus latency gene expression.PLoS pathogens · 2024Article
- Epstein-Barr virus-driven B cell lymphoma mediated by a direct LMP1-TRAF6 complex.Nature communications · 2024Article
- Germinal Center Cytokines Driven Epigenetic Control of Epstein-Barr Virus Latency Gene Expression.bioRxiv : the preprint server for biology · 2024Article
- Epstein-Barr virus evades restrictive host chromatin closure by subverting B cell activation and germinal center regulatory loci.Cell reports · 2023Article
- CD137 (4-1BB) requires physically associated cIAPs for signal transduction and antitumor effects.Science advances · 2023Article
- CD40/TRAF1 decreases synovial cell apoptosis in patients with rheumatoid arthritis through JNK/NF-κB pathway.Journal of bone and mineral metabolism · 2022Article
- Time-resolved transcriptomes reveal diverse B cell fate trajectories in the early response to Epstein-Barr virus infection.Cell reports · 2022Article
- Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
The Epstein-Barr virus (EBV) encoded oncoprotein Latent Membrane Protein 1 (LMP1) signals through two C-terminal tail domains to drive cell growth, survival and transformation. The LMP1 membrane-proximal TES1/CTAR1 domain recruits TRAFs to activate MAP kinase, non-canonical and canonical NF-kB pathways, and is critical for EBV-mediated B-cell transformation. TRAF1 is amongst the most highly TES1-induced target genes and is abundantly expressed in EBV-associated lymphoproliferative disorders. We found that TRAF1 expression enhanced LMP1 TES1 domain-mediated activation of the p38, JNK, ERK and canonical NF-kB pathways, but not non-canonical NF-kB pathway activity. To gain insights into how TRAF1 amplifies LMP1 TES1 MAP kinase and canonical NF-kB pathways, we performed proteomic analysis of TRAF1 complexes immuno-purified from cells uninduced or induced for LMP1 TES1 signaling. Unexpectedly, we found that LMP1 TES1 domain signaling induced an association between TRAF1 and the linear ubiquitin chain assembly complex (LUBAC), and stimulated linear (M1)-linked polyubiquitin chain attachment to TRAF1 complexes. LMP1 or TRAF1 complexes isolated from EBV-transformed lymphoblastoid B cell lines (LCLs) were highly modified by M1-linked polyubiqutin chains. The M1-ubiquitin binding proteins IKK-gamma/NEMO, A20 and ABIN1 each associate with TRAF1 in cells that express LMP1. TRAF2, but not the cIAP1 or cIAP2 ubiquitin ligases, plays a key role in LUBAC recruitment and M1-chain attachment to TRAF1 complexes, implicating the TRAF1:TRAF2 heterotrimer in LMP1 TES1-dependent LUBAC activation. Depletion of either TRAF1, or the LUBAC ubiquitin E3 ligase subunit HOIP, markedly impaired LCL growth. Likewise, LMP1 or TRAF1 complexes purified from LCLs were decorated by lysine 63 (K63)-linked polyubiqutin chains. LMP1 TES1 signaling induced K63-polyubiquitin chain attachment to TRAF1 complexes, and TRAF2 was identified as K63-Ub chain target. Co-localization of M1- and K63-linked polyubiquitin chains on LMP1 complexes may facilitate downstream canonical NF-kB pathway activation. Our results highlight LUBAC as a novel potential therapeutic target in EBV-associated lymphoproliferative disorders.
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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.