Publication: A conserved tetraspanin subfamily promotes Notch signaling in Caenorhabditis elegans and in human cells
dc.contributor.coauthor | Sulis, M.L. | |
dc.contributor.coauthor | Ferrando, A.A. | |
dc.contributor.coauthor | Greenwald, I. | |
dc.contributor.department | Department of Molecular Biology and Genetics | |
dc.contributor.kuauthor | Dunn, Cory David | |
dc.contributor.schoolcollegeinstitute | College of Sciences | |
dc.date.accessioned | 2024-11-09T12:11:46Z | |
dc.date.issued | 2010 | |
dc.description.abstract | The cytosolic domain of Notch is a membrane-tethered transcription factor. Ligand binding ultimately leads to γ-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 γ-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 γ-secretase activity. | |
dc.description.fulltext | YES | |
dc.description.indexedby | WOS | |
dc.description.indexedby | Scopus | |
dc.description.openaccess | YES | |
dc.description.publisherscope | International | |
dc.description.sponsoredbyTubitakEu | N/A | |
dc.description.sponsorship | National Institutes of Health-National Center for Research Resources | |
dc.description.sponsorship | National Institutes of Health | |
dc.description.sponsorship | Leukemia and Lymphoma Society | |
dc.description.version | Publisher version | |
dc.identifier.doi | 10.1073/pnas.1001647107 | |
dc.identifier.eissn | 1091-6490 | |
dc.identifier.embargo | NO | |
dc.identifier.filenameinventoryno | IR00890 | |
dc.identifier.issn | 0027-8424 | |
dc.identifier.quartile | Q1 | |
dc.identifier.scopus | 2-s2.0-77950540047 | |
dc.identifier.uri | https://doi.org/10.1073/pnas.1001647107 | |
dc.identifier.wos | 413221100001 | |
dc.keywords | γ-Secretase | |
dc.keywords | Cancer | |
dc.keywords | Development | |
dc.keywords | Gamma secretase | |
dc.keywords | Glucagon like peptide 1 | |
dc.keywords | Notch receptor | |
dc.keywords | Notch1 receptor | |
dc.keywords | RNA | |
dc.keywords | Tetraspanin | |
dc.keywords | Tetraspanin 12 | |
dc.keywords | TSPAN33 protein | |
dc.keywords | TSPAN5 protein | |
dc.keywords | Unclassified drug | |
dc.keywords | Caenorhabditis elegans proteins | |
dc.keywords | Conserved sequence | |
dc.keywords | DNA primers | |
dc.keywords | Germ cells | |
dc.keywords | Hela cells | |
dc.keywords | Humans | |
dc.keywords | Membrane glycoproteins | |
dc.keywords | Membrane proteins | |
dc.keywords | Precursor T-cell lymphoblastic Leukemia-lymphoma | |
dc.keywords | RNA interference | |
dc.keywords | Signal transduction | |
dc.language.iso | eng | |
dc.publisher | National Academy of Sciences | |
dc.relation.grantno | R01CA095389 | |
dc.relation.grantno | R01CA120196 | |
dc.relation.grantno | 1287-08 | |
dc.relation.grantno | 6237-08 | |
dc.relation.ispartof | Proceedings of the National Academy of Sciences of the United States of America | |
dc.relation.uri | http://cdm21054.contentdm.oclc.org/cdm/ref/collection/IR/id/887 | |
dc.subject | Molecular biology and genetics | |
dc.title | A conserved tetraspanin subfamily promotes Notch signaling in Caenorhabditis elegans and in human cells | |
dc.type | Conference Proceeding | |
dspace.entity.type | Publication | |
local.contributor.kuauthor | Dunn, Cory David | |
local.publication.orgunit1 | College of Sciences | |
local.publication.orgunit2 | Department of Molecular Biology and Genetics | |
relation.isOrgUnitOfPublication | aee2d329-aabe-4b58-ba67-09dbf8575547 | |
relation.isOrgUnitOfPublication.latestForDiscovery | aee2d329-aabe-4b58-ba67-09dbf8575547 | |
relation.isParentOrgUnitOfPublication | af0395b0-7219-4165-a909-7016fa30932d | |
relation.isParentOrgUnitOfPublication.latestForDiscovery | af0395b0-7219-4165-a909-7016fa30932d |
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