ArticleTraffic (Copenhagen, Denmark)2010
γ-secretase-dependent cleavage initiates notch signaling from the plasma membrane.
Article in Traffic (Copenhagen, Denmark), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
41 citing papers in PubMed, 66 citations in OpenAlex.
- Article
- Canonical and noncanonical NOTCH signaling in the nongenetic resistance of cancer: distinct and concerted control.Frontiers of medicine · 2025Review
- Arachidonic acid metabolism regulates the development of retinopathy of prematurity among preterm infants.Journal of neurochemistry · 2024Article
- A deficiency screen of the 3rd chromosome for dominant modifiers of the Drosophila ER integral membrane protein, Jagunal.G3 (Bethesda, Md.) · 2023Article
- Therapeutic Potential of Targeting Regulated Intramembrane Proteolysis Mechanisms of Voltage-Gated Ion Channel Subunits and Cell Adhesion Molecules.Pharmacological reviews · 2022Review
- The Potential of Gamma Secretase as a Therapeutic Target for Cardiac Diseases.Journal of personalized medicine · 2021Review
- The Role of Intracellular Trafficking of Notch Receptors in Ligand-Independent Notch Activation.Biomolecules · 2021Review
- DR-5 and DLL-4 mAb Functionalized SLNs of Gamma-Secretase Inhibitors- An Approach for TNBC Treatment.Advanced pharmaceutical bulletin · 2021Review
- Class II phosphatidylinositol 3-kinase-C2α is essential for Notch signaling by regulating the endocytosis of γ-secretase in endothelial cells.Scientific reports · 2021Article
- Variants inBrain communications · 2021Article
- To be more precise: the role of intracellular trafficking in development and pattern formation.Biochemical Society transactions · 2020Review
- Review
- A toolkit of taggedmicroPublication biology · 2020Article
- Elucidating Critical Proteinopathic Mechanisms and Potential Drug Targets in Neurodegeneration.Cellular and molecular neurobiology · 2020Review
- Decoding the PTM-switchboard of Notch.Biochimica et biophysica acta. Molecular cell research · 2019Review
- Review
- Histone deacetylase 6 controls Notch3 trafficking and degradation in T-cell acute lymphoblastic leukemia cells.Oncogene · 2018Article
- PI5P4Kγ functions in DTX1-mediated Notch signaling.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Glycogen synthase kinase 3β inhibition enhances Notch1 recycling.Molecular biology of the cell · 2018Article
- The curious case of vacuolar ATPase: regulation of signaling pathways.Molecular cancer · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Notch signaling is critical to animal development, and its dysregulation leads to human maladies ranging from birth defects to cancer. Although endocytosis is currently thought to promote signal activation by delivering activated Notch to endosome-localized gamma-secretase, the data are controversial and the mechanisms that control Notch endocytosis remain poorly defined. Here, we investigated the relationship between Notch internalization and signaling. siRNA-mediated depletion studies reveal that Notch endocytosis is clathrin-dependent and requires epsin1, the adaptor protein complex (AP2) and Nedd4. Moreover, we show that epsin1 interaction with Notch is ubiquitin-dependent. Contrary to the current model, we show that internalization defects lead to elevated gamma-secretase-mediated Notch processing and downstream signaling. These results indicate that signal activation occurs independently of Notch endocytosis and that gamma-secretase cleaves Notch at the plasma membrane. These observations support a model where endocytosis serves to downregulate Notch in signal-receiving cells.
Indexed as
Identifiers
What OpenQuestion holds
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.