ArticleThe Journal of biological chemistry2012
Opposing roles for TRAF1 in the alternative versus classical NF-κB pathway in T cells.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 95 citations in OpenAlex.
- TRAF1 S146 is constitutively phosphorylated in OP9-cultured primary chronic lymphocytic leukemia cells by PKN1/2.ImmunoHorizons · 2026Article
- Disrupting the TRAF1/cIAP2 interaction attenuates inflammasome activation and protects against monosodium urate crystal-induced arthritis.ImmunoHorizons · 2025Article
- Helicobacter pylori VacA modulates TRAF1-mediated 4-1BB/NF-kappaB axis to induce host apoptosis and chronic inflammatory damage.Molecular medicine (Cambridge, Mass.) · 2025Article
- A novel TLR4 accessory molecule drives hepatic oncogenesis through tumor-associated macrophages.Cancer letters · 2025Article
- Role of DZ2002 in reducing corneal graft rejection in rats by influencing Th17 activation via inhibition of the PI3K/AKT pathway and downregulation of TRAF1.Open life sciences · 2025Article
- Article
- Differential protein-protein interactions underlie signaling mediated by the TCR and a 4-1BB domain-containing CAR.Science signaling · 2024Article
- Insights on the NF-κB system in polycystic ovary syndrome, attractive therapeutic targets.Molecular and cellular biochemistry · 2024Review
- Identification of a regulatory pathway governing TRAF1 via an arthritis-associated non-coding variant.Cell genomics · 2023Article
- A systems and computational biology perspective on advancing CAR therapy.Seminars in cancer biology · 2023Review
- CD137 (4-1BB) requires physically associated cIAPs for signal transduction and antitumor effects.Science advances · 2023Article
- NFκB signaling in T cell memory.Frontiers in immunology · 2023Review
- NMolecular cancer · 2022Article
- The Role of Tumor Necrosis Factor Associated Factors (TRAFs) in Vascular Inflammation and Atherosclerosis.Frontiers in cardiovascular medicine · 2022Review
- CD137 (4-1BB) costimulation of CD8Nature communications · 2021Article
- Inhibitory feedback control of NF-κB signalling in health and disease.The Biochemical journal · 2021Review
- 4-1BBL as a Mediator of Cross-Talk between Innate, Adaptive, and Regulatory Immunity against Cancer.International journal of molecular sciences · 2021Review
- The PKN1- TRAF1 signaling axis as a potential new target for chronic lymphocytic leukemia.Oncoimmunology · 2021Article
- Tumor necrosis family receptor superfamily member 9/tumor necrosis factor receptor-associated factor 1 pathway on hepatitis C viral persistence and natural history.World journal of hepatology · 2020Review
- TRAF family molecules in T cells: Multiple receptors and functions.Journal of leukocyte biology · 2020Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T cells lacking TRAF1 hyperproliferate in response to T cell receptor signaling but have impaired signaling downstream of specific TNFR family members such as 4-1BB. Here we resolve this paradox by showing that while TRAF1 is required for maximal activation of the classical NF-κB pathway downstream of 4-1BB in primary T cells, TRAF1 also restricts the constitutive activation of NIK in anti-CD3-activated T cells. Activation of the alternative NF-κB pathway is restricted in unstimulated cells by a cIAP1/2:TRAF2:TRAF3:NIK complex. Using knockdown of NIK by siRNA we show that in activated CD8 T cells TRAF1 is also involved in this process and that constitutive activation of the alternative NF-κB pathway is responsible for costimulation independent hyperproliferation and excess cytokine production in TRAF1-deficient CD8 T cells compared with WT CD8 T cells. The T cell costimulatory molecule 4-1BB critically regulates the survival of activated and memory CD8 T cells. We demonstrate that stimulation through 4-1BB induces cIAP1-dependent TRAF3 degradation and activation of the alternative NF-κB pathway. We also show that while both TRAF1 and cIAP1 have non-redundant roles in suppressing the alternative NF-κB pathway in T cells activated in the absence of costimulation, activation of the classical NF-κB pathway downstream of 4-1BB requires TRAF1, whereas cIAP1 plays a redundant role with cIAP2. Collectively these results demonstrate that TRAF1 plays a critical role in regulating T cell activation both through restricting the costimulation independent activation of NIK in activated T cells and by promoting the 4-1BB-induced classical NF-κB pathway.
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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.