ArticleFrontiers in immunology2013
A Complex Relationship between TRAF3 and Non-Canonical NF-κB2 Activation in B Lymphocytes.
Article in Frontiers in immunology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 32 citations in OpenAlex.
- Syk inhibition limits autoimmunity and abnormal B cell phenotype and function in mice with B cell-specific TRAF3 deficiency.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Clinical applications and challenges of CD40/CD40L signaling regulation in autoimmune diseases.Frontiers in immunology · 2026Review
- Reduction of TRAF3 by heterozygosity or aging impacts B cell function.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- TRAF3 regulation of proximal TLR signaling in B cells.Journal of leukocyte biology · 2024Article
- A review of the literature on the use of CRISPR/Cas9 gene therapy to treat hepatocellular carcinoma.Oncology research · 2024Review
- Multiple mechanisms for TRAF3-mediated regulation of the T cell costimulatory receptor GITR.The Journal of biological chemistry · 2021Article
- Article
- TRAF2 Ser-11 Phosphorylation Promotes Cytosolic Translocation of the CD40 Complex To Regulate Downstream Signaling Pathways.Molecular and cellular biology · 2020Article
- B Cell Dysregulation in Common Variable Immunodeficiency Interstitial Lung Disease.Frontiers in immunology · 2020Review
- TRAF3 regulates the oncogenic proteins Pim2 and c-Myc to restrain survival in normal and malignant B cells.Scientific reports · 2019Article
- Targeting CD40-Induced TRAF6 Signaling in Macrophages Reduces Atherosclerosis.Journal of the American College of Cardiology · 2018Article
- Dysregulated TRAF3 and BCL2 Expression Promotes Multiple Classes of Mature Non-hodgkin B Cell Lymphoma in Mice.Frontiers in immunology · 2018Article
- TRAF3 as a Multifaceted Regulator of B Lymphocyte Survival and Activation.Frontiers in immunology · 2018Review
- BAFF and BAFF-Receptor in B Cell Selection and Survival.Frontiers in immunology · 2018Review
- CD137 (4-1BB) Signalosome: Complexity Is a Matter of TRAFs.Frontiers in immunology · 2018Review
- B Cell-Activating Factor (BAFF)-Targeted B Cell Therapies in Inflammatory Bowel Diseases.Digestive diseases and sciences · 2016Review
- TRAF3 as a powerful and multitalented regulator of lymphocyte functions.Journal of leukocyte biology · 2016Review
- Genetic and genomic basis of antibody response to porcine reproductive and respiratory syndrome (PRRS) in gilts and sows.Genetics, selection, evolution : GSE · 2016Article
- Nuclear TRAF3 is a negative regulator of CREB in B cells.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- The adaptor protein TRAF3 inhibits interleukin-6 receptor signaling in B cells to limit plasma cell development.Science signaling · 2015Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The adaptor protein TRAF3 restrains B cell activating factor receptor (BAFFR) and CD40-mediated activation of the NF-κB2 pathway in B cells. Mice lacking TRAF3 specifically in B cells revealed the critical role of TRAF3 in restraining homeostatic B cell survival. Furthermore, loss-of-function mutations of the traf3 gene have been associated with human B cell malignancies, especially multiple myeloma (MM). It has been proposed that receptor-induced TRAF3 degradation leads to stabilization of the NF-κB inducing kinase (NIK), and subsequent NF-κB2 activation. However, it is unclear how receptor-mediated TRAF3 degradation or loss-of-function contributes to B cell-specific NF-κB2 activation. In the current study, we employed two complementary models to address this question. One utilized a mutant traf3 gene found in a human MM-derived cell line called LP1. The LP1 mutant TRAF3 protein lacks the TRAF-N and TRAF-C domains. Consistent with the paradigm described, expression of LP1 TRAF3 in B cells promoted higher basal levels of NF-κB2 activation compared to Wt TRAF3. However, LP1 did not associate with TRAF2, CD40, or BAFFR, and no LP1 degradation was observed following receptor engagement. Interestingly, LP1 showed enhanced NIK association. Thus, TRAF3 degradation becomes dispensable to activate NF-κB2 when it is unable to associate with TRAF2. In a second model, we examined several mutant forms of BAFFR that are unable to induce NF-κB2 activation in B cells. Signaling to B cells by each of these BAFFR mutants, however, induced levels of TRAF3 degradation similar to those induced by Wt BAFFR. Thus, in B cells, receptor-mediated TRAF3 degradation is not sufficient to promote NF-κB2 activation. We thus conclude that there is not a simple linear relationship in B lymphocytes between relative levels of cellular TRAF3, induced TRAF3 degradation, NIK activation, and NF-κB2 activation.
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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.