ArticleMolecular and cellular biology2015
Notch1 Autoactivation via Transcriptional Regulation of Furin, Which Sustains Notch1 Signaling by Processing Notch1-Activating Proteases ADAM10 and Membrane Type 1 Matrix Metalloproteinase.
Article in Molecular and cellular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- RND3 Potentiates Proinflammatory Activation through NOTCH Signaling in Activated Macrophages.Journal of immunology research · 2024Article
- Furin as a therapeutic target in cystic fibrosis airways disease.European respiratory review : an official journal of the European Respiratory Society · 2023Review
- Review
- Sulindac sulfide as a non-immune suppressive γ-secretase modulator to target triple-negative breast cancer.Frontiers in immunology · 2023Article
- NOTCH signaling in COVID-19: a central hub controlling genes, proteins, and cells that mediate SARS-CoV-2 entry, the inflammatory response, and lung regeneration.Frontiers in cellular and infection microbiology · 2022Article
- Molecular pathways involved in COVID-19 and potential pathway-based therapeutic targets.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Review
- Molecular Insights into the Crosstalk Between Immune Inflammation Nexus and SARS-CoV-2 Virus.Current microbiology · 2021Review
- ADAM10 Site-Dependent Biology: Keeping Control of a Pervasive Protease.International journal of molecular sciences · 2021Review
- Performance Assessment of the Network Reconstruction Approaches on Various Interactomes.Frontiers in molecular biosciences · 2021Article
- The Notch Pathway: A Link Between COVID-19 Pathophysiology and Its Cardiovascular Complications.Frontiers in cardiovascular medicine · 2021Review
- NOTCH3 signaling is essential for NF-κB activation in TLR-activated macrophages.Scientific reports · 2020Article
- Prometastatic secretome trafficking via exosomes initiates pancreatic cancer pulmonary metastasis.Cancer letters · 2020Article
- Methylglyoxal couples metabolic and translational control of Notch signalling in mammalian neural stem cells.Nature communications · 2020Article
- COVID-19 in the heart and the lungs: could we "Notch" the inflammatory storm?Basic research in cardiology · 2020Article
- A Disintegrin and Metalloproteinase-Control Elements in Infectious Diseases.Frontiers in cardiovascular medicine · 2020Review
- Article
- The expression of the nicotinic acetylcholine receptor α3 subunit in the brains of patients with Alzheimer's disease and its effects on α- and γ-secretases and Notch signal transduction in SH-SY5Y cells.International journal of clinical and experimental pathology · 2019Article
- Doxorubicin combined with Notch1-targeting siRNA for the treatment of gastric cancer.Oncology letters · 2018Article
- Notch1 signaling in melanoma cells promoted tumor-induced immunosuppression via upregulation of TGF-β1.Journal of experimental & clinical cancer research : CR · 2018Article
- Proprotein convertase inhibition promotes ciliated cell differentiation - a potential mechanism for the inhibition of Notch1 signalling by decanoyl-RVKR-chloromethylketone.Journal of tissue engineering and regenerative medicine · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Notch1 is an evolutionarily conserved transmembrane receptor involved in melanoma growth. Notch1 is first cleaved by furin in the Golgi apparatus to produce the biologically active heterodimer. Following ligand binding, Notch1 is cleaved at the cell membrane by proteases such as ADAM10 and -17 and membrane type 1 matrix metalloproteinase (MT1-MMP), the latter of which we recently identified as a novel protease involved in Notch1 processing. The final cleavage is γ-secretase dependent and releases the active Notch intracellular domain (NIC). We now demonstrate that Notch1 directly regulates furin expression. Aside from activating Notch1, furin cleaves and activates several proteases, including MT1-MMP, ADAM10, and ADAM17. By chromatin immunoprecipitation and a reporter assay, we demonstrate that Notch1 binds at position -1236 of the furin promoter and drives furin expression. The Notch1-dependent enhancement of furin expression increases the activities of MT1-MMP and ADAM10 but not that of ADAM17, as demonstrated by short hairpin RNA (shRNA) knockdown of furin, and promotes the cleavage of Notch1 itself. These data highlight a novel positive-feedback loop whereby Notch1-dependent furin expression can induce Notch1 signaling by increasing Notch1 processing and by potentiating the activity of the proteases responsible for Notch1 activation. This leads to Notch1 signal amplification, which can promote melanoma tumor growth and progression, as demonstrated by the inhibition of cell migration and invasion upon furin inhibition downstream of Notch1. Disruption of such feedback signaling might represent an avenue for the treatment of melanoma.
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