ArticleNature2011
Acetylation-dependent regulation of endothelial Notch signalling by the SIRT1 deacetylase.
Article in Nature, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 185 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
185 citing papers in PubMed, 1 synthesis or guideline pooled it, 374 citations in OpenAlex.
- Sirtuin1 in Spinal Cord Injury: Regulatory Mechanisms, Microenvironment Remodeling and Therapeutic Potential.CNS neuroscience & therapeutics · 2025Pooled it
- Ticagrelor IncreasesInternational journal of molecular sciences · 2020Trial
- Notch receptors in breast cancer: context-dependent roles and therapeutic targeting.Cell communication and signaling : CCS · 2026Review
- SIRT1 regulates CaOx crystal-induced exacerbation of renal mitochondrial dysfunction and fibrosis through PPAR-α in aged mice.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Single-cell insights into maladaptive endothelial plasticity and therapeutic targets in diabetic vascular complications.Cardiovascular diabetology · 2026Review
- Posttranslational modifications in regulating Notch signaling pathway and tumor angiogenesis: from molecular mechanisms to therapeutic applications.Journal of molecular cell biology · 2026Review
- Bmp9 regulates Notch signaling and the temporal dynamics of angiogenesis via Lunatic Fringe.Developmental cell · 2026Article
- NOTCH1 intracellular domain stabilization by MDM2 plays a major role in NSCLC response to platinum.EMBO molecular medicine · 2026Article
- What role does the Notch signaling pathway play in exercise-related metabolic and neurological adaptations? A molecular-to-systems perspective.Frontiers in physiology · 2026Review
- Article
- Aging and lung diseases: Unraveling mechanisms and therapeutic targets.Chinese medical journal pulmonary and critical care medicine · 2025Review
- Endothelial cell metabolism in cardiovascular physiology and disease.Nature reviews. Cardiology · 2025Review
- Role of vascular smooth muscle phenotypic transformation induced by histone modifications in the development of abdominal aortic aneurysms.Clinical epigenetics · 2025Review
- Reversion of aortic valve cells calcification by activation of Notch signalling via histone acetylation induction.Signal transduction and targeted therapy · 2025Article
- Metabolic Stress-Induced Choline Kinase α (CHKA) Activation in Endothelial Subpopulation Contributes to Diabetes-Associated Microvascular Dysfunction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Temporal dynamics of angiogenesis: the emerging role of mechanoregulated pathways.Biochemical Society transactions · 2025Review
- The Memory Gene,Biomolecules · 2025Article
- Modes of Notch signalling in development and disease.Nature reviews. Molecular cell biology · 2025Review
- Notch signaling pathway modulation by food functional ingredients: mechanisms, cancer and immunoregulation.Frontiers in cell and developmental biology · 2025Review
- Pediatric cancer-pathology and microenvironment influence: a perspective into osteosarcoma and non-osteogenic mesenchymal malignant neoplasms.Discover oncology · 2024Review
125 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 5 countries.
Funding
Abstract
Notch signalling is a key intercellular communication mechanism that is essential for cell specification and tissue patterning, and which coordinates critical steps of blood vessel growth. Although subtle alterations in Notch activity suffice to elicit profound differences in endothelial behaviour and blood vessel formation, little is known about the regulation and adaptation of endothelial Notch responses. Here we report that the NAD(+)-dependent deacetylase SIRT1 acts as an intrinsic negative modulator of Notch signalling in endothelial cells. We show that acetylation of the Notch1 intracellular domain (NICD) on conserved lysines controls the amplitude and duration of Notch responses by altering NICD protein turnover. SIRT1 associates with NICD and functions as a NICD deacetylase, which opposes the acetylation-induced NICD stabilization. Consequently, endothelial cells lacking SIRT1 activity are sensitized to Notch signalling, resulting in impaired growth, sprout elongation and enhanced Notch target gene expression in response to DLL4 stimulation, thereby promoting a non-sprouting, stalk-cell-like phenotype. In vivo, inactivation of Sirt1 in zebrafish and mice causes reduced vascular branching and density as a consequence of enhanced Notch signalling. Our findings identify reversible acetylation of the NICD as a molecular mechanism to adapt the dynamics of Notch signalling, and indicate that SIRT1 acts as rheostat to fine-tune endothelial Notch responses.
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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.