ArticleProceedings of the National Academy of Sciences of the United States of America2010
A conserved tetraspanin subfamily promotes Notch signaling in Caenorhabditis elegans and in human cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 62 citations in OpenAlex.
- Article
- Tetraspanin TSP-12 and SUP-17/ADAM10 exhibit cell type-specific codependence for trafficking through the Golgi.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Cldn11 deficiency aggravates osteoarthritis by inhibiting Notch signalling in a Tspan5-dependent manner.Journal of orthopaedic surgery and research · 2026Article
- Identification of a potential internalization or endocytic compartment-targeting signal in the C-terminal tail of the tetraspanin protein TSP-12.microPublication biology · 2026Article
- Tetraspanins affect membrane structures and the trafficking of molecular partners: what impact on extracellular vesicles?Biochemical Society transactions · 2025Review
- New Report of a Different Clinical Presentation ofMolecular syndromology · 2022Article
- MiR-322-5p Alleviates Cell Injury and Impairment of Cognitive Function in Vascular Dementia by Targeting TSPAN5.Yonsei medical journal · 2022Article
- The C. elegans TspanC8 tetraspanin TSP-14 exhibits isoform-specific localization and function.PLoS genetics · 2022Article
- Tspan5 promotes epithelial-mesenchymal transition and tumour metastasis of hepatocellular carcinoma by activating Notch signalling.Molecular oncology · 2021Article
- Review
- Tetraspanins as Potential Modulators of Glutamatergic Synaptic Function.Frontiers in molecular neuroscience · 2021Review
- Tetraspanins TSP-12 and TSP-14 function redundantly to regulate the trafficking of the type II BMP receptor inProceedings of the National Academy of Sciences of the United States of America · 2020Article
- TspanC8 tetraspanins differentially regulate ADAM10 endocytosis and half-life.Life science alliance · 2020Article
- TSPAN5 Enriched Microdomains Provide a Platform for Dendritic Spine Maturation through Neuroligin-1 Clustering.Cell reports · 2019Article
- Transcriptome profiling revealed multiple genes and ECM-receptor interaction pathways that may be associated with breast cancer.Cellular & molecular biology letters · 2019Article
- OrthoList 2: A New Comparative Genomic Analysis of Human andGenetics · 2018Article
- Article
- Immune Targeting of Tetraspanins Involved in Cell Invasion and Metastasis.Frontiers in immunology · 2018Review
- Genetic and biochemical changes of the serotonergic system in migraine pathobiology.The journal of headache and pain · 2017Review
- Tetraspanin 6: a pivotal protein of the multiple vesicular body determining exosome release and lysosomal degradation of amyloid precursor protein fragments.Molecular neurodegeneration · 2017Article
Corrections and comments
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Authors and funding
4 authors at 4 institutions in 3 countries.
Funding
Abstract
The cytosolic domain of Notch is a membrane-tethered transcription factor. Ligand binding ultimately leads to gamma-secretase cleavage within the transmembrane domain, allowing the intracellular domain to translocate to the nucleus and activate target gene transcription. Constitutive Notch signaling has been associated with human cancers such as T cell acute lymphoblastic leukemia (T-ALL). As tetraspanins have been implicated in many different signaling processes, we assessed their potential contribution to Notch signaling. We used a genetic assay in Caenorhabditis elegans to identify TSP-12 as a positive factor for Notch activity in several cellular contexts. Then, using a cell culture system, we showed that two human TSP-12 orthologs, TSPAN33 and TSPAN5, promote Notch activity and are likely to act at the gamma-secretase cleavage step. We also acquired evidence for functional redundancy among tetraspanins in both C. elegans and human cells. Selective inhibition of tetraspanins may constitute an anti-NOTCH therapeutic approach to reduce gamma-secretase activity.
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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.