ArticleJournal of molecular cell biology2020
NUMB enhances Notch signaling by repressing ubiquitination of NOTCH1 intracellular domain.
Article in Journal of molecular cell biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed.
- Bmp9 regulates Notch signaling and the temporal dynamics of angiogenesis via Lunatic Fringe.Developmental cell · 2026Article
- Uncovering the role of integrated stress in Alzheimer's disease through single-cell and transcriptomic analysis.Scientific reports · 2026Article
- Lymphatic-stem cell crosstalk promotes tendon regeneration via Notch1-Srebp2-mediated cholesterol metabolism.Nature communications · 2025Article
- Regulation of Notch signaling by multiple Ankyrin repeat containing protein Mask.Cell communication and signaling : CCS · 2025Article
- The Roles of the Numb Protein in Synaptic Development and Plasticity.Developmental neurobiology · 2025Article
- Melatonin Exerts Positive Effects on Sepsis Through Various Beneficial Mechanisms.Drug design, development and therapy · 2025Review
- Despicable role of epithelial-mesenchymal transition in breast cancer metastasis: ExhibitingCancer pathogenesis and therapy · 2025Review
- RAB4A is a master regulator of cancer cell stemness upstream of NUMB-NOTCH signaling.Cell death & disease · 2024Article
- Genetic Signatures of Positive Selection in Human Populations Adapted to High Altitude in Papua New Guinea.Genome biology and evolution · 2024Article
- Article
- FBP1 inhibits NSCLC stemness by promoting ubiquitination of Notch1 intracellular domain and accelerating degradation.Cellular and molecular life sciences : CMLS · 2024Article
- Molecular pathways and targeted therapies in head and neck cancers pathogenesis.Frontiers in oncology · 2024Review
- Expression and clinical significance of Numb and Notch-1 proteins between tissue of colon cancer and regional lymph node metastases.Frontiers in oncology · 2024Article
- SSH3 promotes pancreatic cancer proliferation and migration by activating the notch signaling pathway.American journal of cancer research · 2024Article
- Article
- Modulation of Notch Signaling by Small-Molecular Compounds and Its Potential in Anticancer Studies.Cancers · 2023Review
- BAP1-related signature predicts benefits from immunotherapy over VEGFR/mTOR inhibitors in ccRCC: a retrospective analysis of JAVELIN Renal 101 and checkmate-009/010/025 trials.Cancer immunology, immunotherapy : CII · 2023Article
- The Intricate Notch Signaling Dynamics in Therapeutic Realms of Cancer.ACS pharmacology & translational science · 2023Review
- HIV-1 exploits Hes-1 expression during pre-existing HPV-16 infection for cancer progression.Virusdisease · 2023Article
- Review
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The release and nuclear translocation of the intracellular domain of Notch receptor (NICD) is the prerequisite for Notch signaling-mediated transcriptional activation. NICD is subjected to various posttranslational modifications including ubiquitination. Here, we surprisingly found that NUMB proteins stabilize the intracellular domain of NOTCH1 receptor (N1ICD) by regulating the ubiquitin-proteasome machinery, which is independent of NUMB's role in modulating endocytosis. BAP1, a deubiquitinating enzyme (DUB), was further identified as a positive N1ICD regulator, and NUMB facilitates the association between N1ICD and BAP1 to stabilize N1ICD. Intriguingly, BAP1 stabilizes N1ICD independent of its DUB activity but relying on the BRCA1-inhibiting function. BAP1 strengthens Notch signaling and maintains stem-like properties of cortical neural progenitor cells. Thus, NUMB enhances Notch signaling by regulating the ubiquitinating activity of the BAP1-BRCA1 complex.
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Registered trials
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