ArticleProceedings of the National Academy of Sciences of the United States of America2009
TRAF5 is a critical mediator of in vitro signals and in vivo functions of LMP1, the viral oncogenic mimic of CD40.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. 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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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- Identification of a systemic lupus erythematosus disease signature in resting naive B cells.The Journal of clinical investigation · 2026Article
- The Role of Tumor Necrosis Factor Associated Factors (TRAFs) in Vascular Inflammation and Atherosclerosis.Frontiers in cardiovascular medicine · 2022Review
- Toll-like receptor signalling in B cells during systemic lupus erythematosus.Nature reviews. Rheumatology · 2021Review
- HP1BP3 promotes tumor growth and metastasis by upregulating miR-23a to target TRAF5 in esophageal squamous cell carcinoma.American journal of cancer research · 2021Article
- Epstein-Barr Functional Mimicry: Pathogenicity of Oncogenic Latent Membrane Protein-1 in Systemic Lupus Erythematosus and Autoimmunity.Frontiers in immunology · 2020Article
- Review
- The Epstein-Barr virus LMP1 interactome: biological implications and therapeutic targets.Future virology · 2018Article
- Genetic Alterations of TRAF Proteins in Human Cancers.Frontiers in immunology · 2018Review
- Emergence of Members of TRAF and DUB of Ubiquitin Proteasome System in the Regulation of Hypertrophic Cardiomyopathy.Frontiers in genetics · 2018Review
- The oncogenic membrane protein LMP1 sequesters TRAF3 in B-cell lymphoma cells to produce functional TRAF3 deficiency.Blood advances · 2017Article
- Tumor necrosis factor receptor- associated factor 6 (TRAF6) regulation of development, function, and homeostasis of the immune system.Immunological reviews · 2015Review
- A new model of LMP1-MYC interaction in B cell lymphoma.Leukemia & lymphoma · 2014Article
- Roles for TNF-receptor associated factor 3 (TRAF3) in lymphocyte functions.Cytokine & growth factor reviews · 2014Review
- TRAF6 is a critical regulator of LMP1 functions in vivo.International immunology · 2014Article
- TRAF5 negatively regulates TLR signaling in B lymphocytes.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- TRAF5 and TRAF3IP2 gene polymorphisms are associated with Behçet's disease and Vogt-Koyanagi-Harada syndrome: a case-control study.PloS one · 2014Article
- TRAF molecules in cell signaling and in human diseases.Journal of molecular signaling · 2013Article
- Up-regulation and pre-activation of TRAF3 and TRAF5 in inflammatory bowel disease.International journal of medical sciences · 2013Article
- TRAF binding is required for a distinct subset of in vivo B cell functions of the oncoprotein LMP1.Journal of immunology (Baltimore, Md. : 1950) · 2012Article
- Epstein-Barr virus LMP2A reduces hyperactivation induced by LMP1 to restore normal B cell phenotype in transgenic mice.PLoS pathogens · 2012Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
The cytoplasmic signaling protein TNF receptor-associated factor 5 (TRAF5) has been implicated in several biological roles in T-lymphocyte responses. However, a clear connection between in vivo TRAF5 immune cell functions and specific signaling pathways has not been made. This study shows that TRAF5 associated strongly with the viral oncogenic CD40 mimic latent membrane protein 1 (LMP1), in contrast to weaker association with CD40, for which it has been shown to play a modest role. LMP1 uses specific TRAFs differently than CD40, resulting in amplified and dysregulated CD40-like activation of B lymphocytes. When the cytoplasmic domain of LMP1 is expressed as a transgenic replacement for CD40 in mouse B cells, the resulting mouse exhibits measures of B-cell hyperactivity such as splenomegaly, lymphadenopathy, elevated serum IL-6, elevated serum autoantibodies, and abnormal splenic architecture. Thus, in contrast to CD40, TRAF5 may have an important nonredundant role as a positive mediator of LMP1 signaling and functions in B cells. To test this hypothesis, mice were created that express mCD40LMP1 in place of CD40, and are either sufficient or deficient in TRAF5. Results revealed that TRAF5 plays a critical role in LMP1-mediated c-Jun kinase signaling and is required for much of the abnormal phenotype observed in mCD40LMP1 transgenic mice. This is the first report showing a major requirement for TRAF5 in signaling by a specific receptor both in vitro and in vivo, as well as playing an important role in biological function in B lymphocytes.
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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.