ArticleScience signaling2014
T cell receptor signals to NF-κB are transmitted by a cytosolic p62-Bcl10-Malt1-IKK signalosome.
Article in Science signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- Lck regulates T cell activation through phosphorylation of p62.EMBO reports · 2026Article
- A PBD dimer-containing antibody-drug conjugate targeting CCRL2 for high-risk MDS/AML including TP53-mutated disease.Blood advances · 2026Article
- TRBC2-targeting antibody-drug conjugates for the treatment of T cell cancers.Nature cancer · 2025Article
- Article
- IL-18 serves as a main effector of CAF-derived METTL3 against immunosuppression of NSCLC via driving NF-κB pathway.Epigenetics · 2023Article
- Autophagy-associated immune dysregulation and hyperplasia in a patient with compound heterozygous mutations inAutophagy · 2023Article
- Impact of ROS-Dependent Lipid Metabolism on Psoriasis Pathophysiology.International journal of molecular sciences · 2022Review
- DEAD-Box Helicase 3 X-Linked Promotes Metastasis by Inducing Epithelial-Mesenchymal Transition via p62/Sequestosome-1.Digestive diseases and sciences · 2021Article
- Signaling through polymerization and degradation: Analysis and simulations of T cell activation mediated by Bcl10.PLoS computational biology · 2021Article
- Gain-of-function mutations in CARD11 promote enhanced aggregation and idiosyncratic signalosome assembly.Cellular immunology · 2020Article
- The Tripartite Nexus: Autophagy, Cancer, and Tripartite Motif-Containing Protein Family Members.Frontiers in pharmacology · 2020Review
- SQSTM-1/p62 potentiates HTLV-1 Tax-mediated NF-κB activation through its ubiquitin binding function.Scientific reports · 2019Article
- TAK1 converts Sequestosome 1/p62 from an autophagy receptor to a signaling platform.EMBO reports · 2019Article
- Altered Lipid Metabolism in Blood Mononuclear Cells of Psoriatic Patients Indicates Differential Changes in Psoriasis Vulgaris and Psoriatic Arthritis.International journal of molecular sciences · 2019Article
- Supramolecular Complexes in Cell Death and Inflammation and Their Regulation by Autophagy.Frontiers in cell and developmental biology · 2019Review
- Role of IκB kinase β in regulating the remodeling of the CARMA1-Bcl10-MALT1 complex.Biochemical and biophysical research communications · 2018Article
- The Many Roles of Ubiquitin in NF-κB Signaling.Biomedicines · 2018Review
- Impaired Control of Epstein-Barr Virus Infection in B-Cell Expansion with NF-κB and T-Cell Anergy Disease.Frontiers in immunology · 2018Review
- Mechanisms of Regulated and Dysregulated CARD11 Signaling in Adaptive Immunity and Disease.Frontiers in immunology · 2018Review
- CARMA3 Is a Critical Mediator of G Protein-Coupled Receptor and Receptor Tyrosine Kinase-Driven Solid Tumor Pathogenesis.Frontiers in immunology · 2018Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Antigen-mediated stimulation of the T cell receptor (TCR) triggers activation of nuclear factor κB (NF-κB), a key transcriptional regulator of T cell proliferation and effector cell differentiation. TCR signaling to NF-κB requires both the Carma1-Bcl10-Malt1 (CBM) complex and the inhibitor of κB (IκB) kinase (IKK) complex; however, the molecular mechanisms connecting the CBM complex to activation of IKK are incompletely defined. We found that the active IKK complex is a component of a TCR-dependent cytosolic Bcl10-Malt1 signalosome containing the adaptor protein p62, which forms in effector T cells. Phosphorylated IκBα and NF-κB were transiently recruited to this signalosome before NF-κB translocated to the nucleus. Inhibiting the activity of the kinase TAK1 or IKK blocked the phosphorylation of IKK, but not the formation of p62-Bcl10-Malt1 clusters, suggesting that activation of IKK occurs after signalosome assembly. Furthermore, analysis of T cells from p62-deficient mice demonstrated that the p62-dependent clustering of signaling components stimulated activation of NF-κB in effector T cells. Thus, TCR-stimulated activation of NF-κB requires the assembly of cytosolic p62-Bcl10-Malt1-IKK signalosomes, which may ensure highly regulated activation of NF-κB in response to TCR engagement.
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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.