ArticleGenes & development2009
Pre-TCR signaling inactivates Notch1 transcription by antagonizing E2A.
Article in Genes & development, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
108 citing papers in PubMed, 191 citations in OpenAlex.
- Specific Notch receptor-ligand interactions control human TCR-αβ/γδ development by inducing differential Notch signal strength.The Journal of experimental medicine · 2013Trial
- Notch interaction with RUNX factors regulates initiation of the T-lineage program.The Journal of experimental medicine · 2026Article
- Tumor-Associated Glycan Exploits Adenosine Receptor 2A Signaling to Facilitate Immune Evasion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Native stem cell transcriptional circuits define cardinal features of high-risk leukemia.The Journal of experimental medicine · 2025Article
- The epigenetic landscape of fate decisions in T cells.Nature immunology · 2025Review
- A feedback amplifier circuit with Notch and E2A orchestrates T-cell fate and suppresses the innate lymphoid cell lineages during thymic ontogeny.Genes & development · 2025Article
- Food for thought: Nutrient metabolism controlling early T cell development.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- T Cell Development: From T-Lineage Specification to Intrathymic Maturation.Advances in experimental medicine and biology · 2025Review
- Disruption of Notch signaling by KGF induces a developmental pause in thymocytes.Frontiers in immunology · 2025Article
- 17β-estradiol inhibits Notch1 activation in murine macrophage cell line RAW 264.7.Molecular biology reports · 2024Article
- Article
- Transcriptional network dynamics in early T cell development.The Journal of experimental medicine · 2024Review
- Triptolide, a Cancer Cell Proliferation Inhibitor, Causes Zebrafish Muscle Defects by Regulating Notch and STAT3 Signaling Pathways.International journal of molecular sciences · 2024Article
- CaInternational journal of molecular sciences · 2023Article
- Notch Partners in the Long Journey of T-ALL Pathogenesis.International journal of molecular sciences · 2023Review
- Stepwise progression of β-selection during T cell development involves histone deacetylation.Life science alliance · 2023Article
- The β-selection step shapes T-cell identity.Nature · 2023Article
- Generation of T-cell-receptor-negative CD8αβ-positive CAR T cells from T-cell-derived induced pluripotent stem cells.Nature biomedical engineering · 2022Article
- Fine-tuning Notch1 by the stage-specific enhancer.Nature immunology · 2022Article
- A double-negative thymocyte-specific enhancer augments Notch1 signaling to direct early T cell progenitor expansion, lineage restriction and β-selection.Nature immunology · 2022Article
48 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Precise control of the timing and magnitude of Notch signaling is essential for the normal development of many tissues, but the feedback loops that regulate Notch are poorly understood. Developing T cells provide an excellent context to address this issue. Notch1 signals initiate T-cell development and increase in intensity during maturation of early T-cell progenitors (ETP) to the DN3 stage. As DN3 cells undergo beta-selection, during which cells expressing functionally rearranged TCRbeta proliferate and differentiate into CD4(+)CD8(+) progeny, Notch1 signaling is abruptly down-regulated. In this report, we investigate the mechanisms that control Notch1 expression during thymopoiesis. We show that Notch1 and E2A directly regulate Notch1 transcription in pre-beta-selected thymocytes. Following successful beta-selection, pre-TCR signaling rapidly inhibits Notch1 transcription via signals that up-regulate Id3, an E2A inhibitor. Consistent with a regulatory role for Id3 in Notch1 down-regulation, post-beta-selected Id3-deficient thymocytes maintain Notch1 transcription, whereas enforced Id3 expression decreases Notch1 expression and abrogates Notch1-dependent T-cell survival. These data provide new insights into Notch1 regulation in T-cell progenitors and reveal a direct link between pre-TCR signaling and Notch1 expression during thymocyte development. Our findings also suggest new strategies for inhibiting Notch1 signaling in pathologic conditions.
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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.