ArticleThe Journal of experimental medicine2015
Loss of the Notch effector RBPJ promotes tumorigenesis.
Article in The Journal of experimental medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
What it found
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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
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Functional Gene Expression Differentiation of the Notch Signaling Pathway in Female Reproductive Tract Tissues-A Comprehensive Review With Analysis.Frontiers in cell and developmental biology · 2020Pooled it
- Genomic alterations in high-risk chronic lymphocytic leukemia frequently affect cell cycle key regulators and NOTCH1-regulated transcription.Haematologica · 2020Trial
- Inhibition of RBPJ transcription complex promotes IL-17 and IFN-γ secretion by CD4⁺ T cells in hepatocellular carcinoma.Archives of pharmacal research · 2025Article
- Examining the role of Notch signaling in dysplastic lung repair.BMC research notes · 2025Article
- Molecular docking andToxicology reports · 2024Article
- Notch signaling, hypoxia, and cancer.Frontiers in oncology · 2023Review
- Regulation of the THRA gene, encoding the thyroid hormone nuclear receptor TRα1, in intestinal lesions.Molecular oncology · 2022Article
- Genetic Inactivation ofCancers · 2022Article
- FBXO42 facilitates Notch signaling activation and global chromatin relaxation by promoting K63-linked polyubiquitination of RBPJ.Science advances · 2022Article
- Notch-dependent and -independent functions of transcription factor RBPJ.Nucleic acids research · 2022Article
- Chromatin accessibility landscape and active transcription factors in primary human invasive lobular and ductal breast carcinomas.Breast cancer research : BCR · 2022Article
- Exosomal circRNA BTG2 derived from RBP-J overexpressed-macrophages inhibits glioma progression via miR-25-3p/PTEN.Cell death & disease · 2022Article
- COVID-19 and dys-regulation of pulmonary endothelium: implications for vascular remodeling.Cytokine & growth factor reviews · 2022Review
- Aberrant Notch signaling in gliomas: a potential landscape of actionable converging targets for combination approach in therapies resistance.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Alcohol drinking inhibits NOTCH-PAX9 signaling in esophageal squamous epithelial cells.The Journal of pathology · 2021Article
- Article
- NOTCH Signaling Controls Ciliary Body Morphogenesis and Secretion by Directly Regulating Nectin Protein Expression.Cell reports · 2021Article
- Exosomal LncRNA LBX1-AS1 Derived From RBPJ Overexpressed-Macrophages Inhibits Oral Squamous Cell Carcinoma ProgressFrontiers in oncology · 2021Article
- Deficiency of Notch signaling in pericytes results in arteriovenous malformations.JCI insight · 2020Article
- A Molecular Test for Quantifying Functional Notch Signaling Pathway Activity in Human Cancer.Cancers · 2020Article
Corrections and comments
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Authors and funding
21 authors at 4 institutions in 3 countries.
Funding
Abstract
Aberrant Notch activity is oncogenic in several malignancies, but it is unclear how expression or function of downstream elements in the Notch pathway affects tumor growth. Transcriptional regulation by Notch is dependent on interaction with the DNA-binding transcriptional repressor, RBPJ, and consequent derepression or activation of associated gene promoters. We show here that RBPJ is frequently depleted in human tumors. Depletion of RBPJ in human cancer cell lines xenografted into immunodeficient mice resulted in activation of canonical Notch target genes, and accelerated tumor growth secondary to reduced cell death. Global analysis of activated regions of the genome, as defined by differential acetylation of histone H4 (H4ac), revealed that the cell death pathway was significantly dysregulated in RBPJ-depleted tumors. Analysis of transcription factor binding data identified several transcriptional activators that bind promoters with differential H4ac in RBPJ-depleted cells. Functional studies demonstrated that NF-κB and MYC were essential for survival of RBPJ-depleted cells. Thus, loss of RBPJ derepresses target gene promoters, allowing Notch-independent activation by alternate transcription factors that promote tumorigenesis.
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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.