ArticleCellular & molecular immunology2021
TRAF2 regulates T cell immunity by maintaining a Tpl2-ERK survival signaling axis in effector and memory CD8 T cells.
Article in Cellular & molecular immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 16 citations in OpenAlex.
- Deconjugating taurocholic acid with Bifidobacterium to mitigate obesity-driven cancer progression by restoring CD8NPJ biofilms and microbiomes · 2025Article
- Inflammation and cancer cell survival: TRAF2 as a key player.Cell death & disease · 2025Review
- The role of TRAF2 in pan-cancer revealed by integrating informatics and experimental validation.Frontiers in pharmacology · 2025Article
- 4-1BB-encoding CAR causes cell death via sequestration of the ubiquitin-modifying enzyme A20.Cellular & molecular immunology · 2024Article
- Eosinophils promote CD8Signal transduction and targeted therapy · 2024Article
- Balancing activation and co-stimulation of CAR tunes signaling dynamics and enhances therapeutic potency.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- TRAF2 as a key candidate gene in clinical hepatitis B-associated liver fibrosis.Frontiers in molecular biosciences · 2023Article
- Establishment of a new prognostic risk model of MAPK pathway-related molecules in kidney renal clear cell carcinoma based on genomes and transcriptomes analysis.Frontiers in oncology · 2023Article
- Signaling Dynamics of TSHR-Specific CAR-T Cells Revealed by FRET-Based Biosensors.Frontiers in cell and developmental biology · 2022Article
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Authors and funding
11 authors at 1 institution in 3 countries.
Funding
Abstract
Generation and maintenance of antigen-specific effector and memory T cells are central events in immune responses against infections. We show that TNF receptor-associated factor 2 (TRAF2) maintains a survival signaling axis in effector and memory CD8 T cells required for immune responses against infections. This signaling axis involves activation of Tpl2 and its downstream kinase ERK by NF-κB-inducing kinase (NIK) and degradation of the proapoptotic factor Bim. NIK mediates Tpl2 activation by stimulating the phosphorylation and degradation of the Tpl2 inhibitor p105. Interestingly, while NIK is required for Tpl2-ERK signaling under normal conditions, uncontrolled NIK activation due to loss of its negative regulator, TRAF2, causes constitutive degradation of p105 and Tpl2, leading to severe defects in ERK activation and effector/memory CD8 T cell survival. Thus, TRAF2 controls a previously unappreciated signaling axis mediating effector/memory CD8 T cell survival and protective immunity.
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Registered trials
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