ArticleDevelopment (Cambridge, England)2015
The intracellular domains of Notch1 and Notch2 are functionally equivalent during development and carcinogenesis.
Article in Development (Cambridge, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 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
62 citing papers in PubMed.
- NOTCH1 reverses immune suppression in small cell lung cancer through reactivation of STING.The Journal of clinical investigation · 2025Trial
- Single-cell and spatial transcriptomics reveal that THBS1 induces radiation resistance in TNBC through the interaction between myCAF and TOPBP1⁺ tumor cells.Journal of translational medicine · 2026Article
- Notch receptors in breast cancer: context-dependent roles and therapeutic targeting.Cell communication and signaling : CCS · 2026Review
- Notch signaling in the embryonic ectoderm promotes periderm cell fate and represses mineralization of vibrissa hair follicles.bioRxiv : the preprint server for biology · 2026Article
- Sympathetic Activation Promotes Kidney Fibrosis in Mice via Macrophage-Derived N2ICD-Enriched Extracellular Vesicles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Immunosuppressive JAG2Cancer communications (London, England) · 2025Article
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- The Mutational and Microenvironmental Landscape of Cutaneous Squamous Cell Carcinoma: A Review.Cancers · 2024Review
- The cellular Notch1 protein promotes KSHV reactivation in an Rta-dependent manner.Journal of virology · 2024Article
- Neurobeachin regulates hematopoietic progenitor differentiation and survival by modulating Notch activity.Blood advances · 2024Article
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- Unraveling paralog-specific Notch signaling through thermodynamics of ternary complex formation and transcriptional activation of chimeric receptors.Protein science : a publication of the Protein Society · 2024Article
- Effect of Valproic Acid on Promoting the Differentiation of Human Embryonic Stem Cells Into Cholangiocyte-Like Cells.Stem cells translational medicine · 2024Article
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- A topographic atlas defines developmental origins of cell heterogeneity in the human embryonic lung.Nature cell biology · 2023Article
- Notch receptor/ligand diversity: contribution to colorectal cancer stem cell heterogeneity.Frontiers in cell and developmental biology · 2023Review
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- Principles of human and mouse nephron development.Nature reviews. Nephrology · 2022Review
- Multiple Mechanisms of NOTCH1 Activation in Chronic Lymphocytic Leukemia: NOTCH1 Mutations and Beyond.Cancers · 2022Review
2 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
9 authors.
Funding
Abstract
Although Notch1 and Notch2 are closely related paralogs and function through the same canonical signaling pathway, they contribute to different outcomes in some cell and disease contexts. To understand the basis for these differences, we examined in detail mice in which the Notch intracellular domains (N1ICD and N2ICD) were swapped. Our data indicate that strength (defined here as the ultimate number of intracellular domain molecules reaching the nucleus, integrating ligand-mediated release and nuclear translocation) and duration (half-life of NICD-RBPjk-MAML-DNA complexes, integrating cooperativity and stability dependent on shared sequence elements) are the factors that underlie many of the differences between Notch1 and Notch2 in all the contexts we examined, including T-cell development, skin differentiation and carcinogenesis, the inner ear, the lung and the retina. We were able to show that phenotypes in the heart, endothelium, and marginal zone B cells are attributed to haploinsufficiency but not to intracellular domain composition. Tissue-specific differences in NICD stability were most likely caused by alternative scissile bond choices by tissue-specific γ-secretase complexes following the intracellular domain swap. Reinterpretation of clinical findings based on our analyses suggests that differences in outcome segregating with Notch1 or Notch2 are likely to reflect outcomes dependent on the overall strength of Notch signals.
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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.