ArticleMolecular and cellular biology2014
Regulated proteolysis of NOTCH2 and NOTCH3 receptors by ADAM10 and presenilins.
Article in Molecular and cellular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 88 citations in OpenAlex.
- The Abelson kinase and the Nedd4 family E3 ligases co-regulate Notch trafficking to limit signaling.The Journal of cell biology · 2025Article
- Signaling pathways and molecular mechanisms involved in the onset and progression of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL); a focus on Notch3 signaling.The journal of headache and pain · 2025Review
- Tetraspanins 10 and 15 support Venezuelan equine encephalitis virus replication in astrocytoma cells.Molecular biology of the cell · 2025Article
- Traumatic brain injury causes early aggregation of beta-amyloid peptides and NOTCH3 reduction in vascular smooth muscle cells of leptomeningeal arteries.Acta neuropathologica · 2025Article
- Article
- A novel lineage-tracing tool reveals that hypoxic tumor cells drive tumor relapse after radiotherapy.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2025Article
- Notch signaling regulates UNC5B to suppress endothelial proliferation, migration, junction activity, and retinal plexus branching.Scientific reports · 2024Article
- Combinatorial expression motifs in signaling pathways.Cell genomics · 2024Article
- DLBCL-associated NOTCH2 mutations escape ubiquitin-dependent degradation and promote chemoresistance.Blood · 2023Article
- Update on the Epidemiology, Pathogenesis, and Biomarkers of Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy.Journal of clinical neurology (Seoul, Korea) · 2023Review
- Extracellular vesicles mediate the communication between multiple myeloma and bone marrow microenvironment in a NOTCH dependent way.Haematologica · 2022Article
- Secretases Related to Amyloid Precursor Protein Processing.Membranes · 2021Review
- BMP7 reduces the fibrocartilage chondrocyte phenotype.Scientific reports · 2021Article
- The Role of Intracellular Trafficking of Notch Receptors in Ligand-Independent Notch Activation.Biomolecules · 2021Review
- Regulation of ADAM10 by the TspanC8 Family of Tetraspanins and Their Therapeutic Potential.International journal of molecular sciences · 2021Review
- Discovery of bone morphogenetic protein 7-derived peptide sequences that attenuate the human osteoarthritic chondrocyte phenotype.Molecular therapy. Methods & clinical development · 2021Article
- Tetraspanins as Potential Modulators of Glutamatergic Synaptic Function.Frontiers in molecular neuroscience · 2021Review
- Biological Significance of NOTCH Signaling Strength.Frontiers in cell and developmental biology · 2021Review
- Evolution of Human Brain Size-Associated NOTCH2NL Genes Proceeds toward Reduced Protein Levels.Molecular biology and evolution · 2020Article
- A lineage-tracing tool to map the fate of hypoxic tumour cells.Disease models & mechanisms · 2020Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
In mammals, there are four NOTCH receptors and five Delta-Jagged-type ligands regulating many aspects of embryonic development and adult tissue homeostasis. NOTCH proteins are type I transmembrane receptors that interact with ligands on adjacent cells and are activated by regulated intramembrane proteolysis (RIP). The activation mechanism of NOTCH1 receptors upon ligand binding is well understood and requires cleavage by ADAM10 metalloproteases prior to intramembranous cleavage by γ-secretase. How the other human NOTCH receptor homologues are activated upon ligand binding is not known. Here, we dissect the proteolytic activation mechanism of the NOTCH2 and NOTCH3 receptors. We show that NOTCH2 and NOTCH3 signaling can be triggered by both Delta-Jagged-type ligands and requires ADAM10 and presenilin-1 or -2. Importantly, we did not find any role for the highly related ADAM17/TACE (tumor necrosis factor alpha-converting enzyme) protease in ligand-induced NOTCH2 or NOTCH3 signaling. These results demonstrate that canonical ligand-induced proteolysis of the NOTCH1, -2, and -3 receptors strictly depends on consecutive cleavage of these receptors by ADAM10 and the presenilin-containing γ-secretase complex, leading to transcriptional activation.
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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.