ArticleProceedings of the National Academy of Sciences of the United States of America2016
Nuclear TRAF3 is a negative regulator of CREB in B cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 51 citations in OpenAlex.
- DUSP12 Regulates NAT10-Mediated RNA Acetylation to Modulate DNA Repair and Therapeutic Response in Hepatocellular Carcinoma.MedComm · 2026Article
- Dual Role of Cancer Epithelial-Specific TRAF3 in Regulating Breast Cancer Cell Survival and Lymphocyte Activity.International journal of molecular sciences · 2026Article
- 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
- 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
- Neuroactive steroids activate membrane progesterone receptors to induce sex specific effects on protein kinase activity.iScience · 2025Article
- Down-regulation of MIR-378A-3P expression associated with inflammation: The effects of restoring its levels.PloS one · 2025Article
- TRAF3 regulation of proximal TLR signaling in B cells.Journal of leukocyte biology · 2024Article
- The TRAF3-DYRK1A-RAD54L2 complex maintains ACE2 expression to promote SARS-CoV-2 infection.Journal of virology · 2024Article
- cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment.Journal of hematology & oncology · 2024Review
- A review of the literature on the use of CRISPR/Cas9 gene therapy to treat hepatocellular carcinoma.Oncology research · 2024Review
- TRAF3: A novel regulator of mitochondrial physiology and metabolic pathways in B lymphocytes.Frontiers in oncology · 2023Review
- The Roles of TRAF3 in Immune Responses.Disease markers · 2023Review
- TRAF3: Guardian of T lymphocyte functions.Frontiers in immunology · 2023Review
- Circ-CREBBP inhibits sperm apoptosis via the PI3K-Akt signaling pathway by sponging miR-10384 and miR-143-3p.Communications biology · 2022Article
- Excess BAFF Alters NR4As Expression Levels and Breg Function of Human Precursor-like Marginal Zone B-Cells in the Context of HIV-1 Infection.International journal of molecular sciences · 2022Article
- The Tumor Suppressor Protein TRAF3 Modulates GSK3 Activity and Susceptibility of B Lymphoma Cells to GSK3 Inhibition.Cancers · 2022Article
- TRAF3 enhances type I interferon receptor signaling in T cells by modulating the phosphatase PTPN22.Science signaling · 2022Article
- Marginal Zone B-Cell Populations and Their Regulatory Potential in the Context of HIV and Other Chronic Inflammatory Conditions.International journal of molecular sciences · 2022Review
- Hepatoprotective effects of sevoflurane against hepatic ischemia-reperfusion injury by regulating microRNA-124-3p-mediated TRAF3/CREB axis.Cell death discovery · 2022Article
- Cytoplasmic and Nuclear Functions of cIAP1.Biomolecules · 2022Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The adaptor protein TNF receptor-associated factor 3 (TRAF3) regulates signaling through B-lymphocyte receptors, including CD40, BAFF receptor, and Toll-like receptors, and also plays a critical role inhibiting B-cell homoeostatic survival. Consistent with these findings, loss-of-function human TRAF3 mutations are common in B-cell cancers, particularly multiple myeloma and B-cell lymphoma. B cells of B-cell-specific TRAF3(-/-) mice (B-Traf3(-/-)) display remarkably enhanced survival compared with littermate control (WT) B cells. The mechanism for this abnormal homeostatic survival is poorly understood, a key knowledge gap in selecting optimal treatments for human B-cell cancers with TRAF3 deficiency. We show here for the first time to our knowledge that TRAF3 is a resident nuclear protein that associates with the transcriptional regulator cAMP response element binding protein (CREB) in both mouse and human B cells. The TRAF-C domain of TRAF3 was necessary and sufficient to localize TRAF3 to the nucleus via a functional nuclear localization signal. CREB protein was elevated in TRAF3(-/-) B cells, without change in mRNA, but with a decrease in CREB ubiquitination. CREB-mediated transcriptional activity was increased in TRAF3-deficient B cells. Consistent with these findings, Mcl-1, an antiapoptotic target of CREB-mediated transcription, was increased in the absence of TRAF3 and enhanced Mcl-1 was suppressed with CREB inhibition. TRAF3-deficient B cells were also preferentially sensitive to survival inhibition with pharmacologic CREB inhibitor. Our results identify a new mechanism by which nuclear TRAF3 regulates B-cell survival via inhibition of CREB stability, information highly relevant to the role of TRAF3 in B-cell malignancies.
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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.