ArticleFrontiers in immunology2014
NOTCH1 Can Initiate NF-κB Activation via Cytosolic Interactions with Components of the T Cell Signalosome.
Article in Frontiers in immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
29 citing papers in PubMed, 49 citations in OpenAlex.
- Jojoba Oil Protects against Chlorpyrifos-Induced Testicular Toxicity by Modulating Notch1/Jagged1-Inflammatory Axis and Oxidative Stress.Cell biochemistry and biophysics · 2026Article
- Another Notch in the Belt of Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2024Review
- Notch signaling, hypoxia, and cancer.Frontiers in oncology · 2023Review
- Notch signaling in oral pre-cancer and oral cancer.Medical oncology (Northwood, London, England) · 2021Review
- CARMA1 is required for Notch1-induced NF-κB activation in SIL-TAL1-negative T cell acute lymphoblastic leukemia.Journal of molecular medicine (Berlin, Germany) · 2021Article
- Targeting Notch in oncology: the path forward.Nature reviews. Drug discovery · 2021Review
- Therapeutic Targeting of Notch Signaling: From Cancer to Inflammatory Disorders.Frontiers in cell and developmental biology · 2021Review
- Spatial regulation and generation of diversity in signaling pathways.Journal of biosciences · 2021Review
- TAO-kinase 3 governs the terminal differentiation of NOTCH2-dependent splenic conventional dendritic cells.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Cell-Penetrating Anti-Protein Kinase C Theta Antibodies Act Intracellularly to Generate Stable, Highly Suppressive Regulatory T Cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Nucleolar localization of the Notch4 intracellular domain underpins its regulation of the cellular response to genotoxic stressors.Cell death discovery · 2020Article
- Specific Targeting of Notch Ligand-Receptor Interactions to Modulate Immune Responses: A Review of Clinical and Preclinical Findings.Frontiers in immunology · 2020Review
- CD28 Signaling Drives Notch Ligand Expression on CD4 T Cells.Frontiers in immunology · 2020Article
- Notch signalling in T cell homeostasis and differentiation.Open biology · 2019Review
- Folic acid deficiency enhanced microglial immune response via the Notch1/nuclear factor kappa B p65 pathway in hippocampus following rat brain I/R injury and BV2 cells.Journal of cellular and molecular medicine · 2019Article
- Modeling CADASIL vascular pathologies with patient-derived induced pluripotent stem cells.Protein & cell · 2019Article
- Cymerus™ iPSC-MSCs significantly prolong survival in a pre-clinical, humanized mouse model of Graft-vs-host disease.Stem cell research · 2019Article
- Ancient Origin of the CARD-Coiled Coil/Bcl10/MALT1-Like Paracaspase Signaling Complex Indicates Unknown Critical Functions.Frontiers in immunology · 2018Article
- Notch and NF-κB: Coach and Players of Regulatory T-Cell Response in Cancer.Frontiers in immunology · 2018Review
- Rotenone Treatment Reveals a Role for Electron Transport Complex I in the Subcellular Localization of Key Transcriptional Regulators During T Helper Cell Differentiation.Frontiers in immunology · 2018Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
T cell stimulation requires the input and integration of external signals. Signaling through the T cell receptor (TCR) is known to induce formation of the membrane-tethered CBM complex, comprising CARMA1, BCL10, and MALT1, which is required for TCR-mediated NF-κB activation. TCR signaling has been shown to activate NOTCH proteins, transmembrane receptors also implicated in NF-κB activation. However, the link between TCR-mediated NOTCH signaling and early events leading to induction of NF-κB activity remains unclear. In this report, we demonstrate a novel cytosolic function for NOTCH1 and show that it is essential to CBM complex formation. Using a model of skin allograft rejection, we show in vivo that NOTCH1 acts in the same functional pathway as PKCθ, a T cell-specific kinase important for CBM assembly and classical NF-κB activation. We further demonstrate in vitro NOTCH1 associates physically with PKCθ and CARMA1 in the cytosol. Unexpectedly, when NOTCH1 expression was abrogated using RNAi approaches, interactions between CARMA1, BCL10, and MALT1 were lost. This failure in CBM assembly reduced inhibitor of kappa B alpha phosphorylation and diminished NF-κB-DNA binding. Finally, using a luciferase gene reporter assay, we show the intracellular domain of NOTCH1 can initiate robust NF-κB activity in stimulated T cells, even when NOTCH1 is excluded from the nucleus through modifications that restrict it to the cytoplasm or hold it tethered to the membrane. Collectively, these observations provide evidence that NOTCH1 may facilitate early events during T cell activation by nucleating the CBM complex and initiating NF-κB signaling.
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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.