Publication:
A conserved tetraspanin subfamily promotes Notch signaling in Caenorhabditis elegans and in human cells

dc.contributor.coauthorSulis, M.L.
dc.contributor.coauthorFerrando, A.A.
dc.contributor.coauthorGreenwald, I.
dc.contributor.departmentDepartment of Molecular Biology and Genetics
dc.contributor.kuauthorDunn, Cory David
dc.contributor.schoolcollegeinstituteCollege of Sciences
dc.date.accessioned2024-11-09T12:11:46Z
dc.date.issued2010
dc.description.abstractThe 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.fulltextYES
dc.description.indexedbyWOS
dc.description.indexedbyScopus
dc.description.openaccessYES
dc.description.publisherscopeInternational
dc.description.sponsoredbyTubitakEuN/A
dc.description.sponsorshipNational Institutes of Health-National Center for Research Resources
dc.description.sponsorshipNational Institutes of Health
dc.description.sponsorshipLeukemia and Lymphoma Society
dc.description.versionPublisher version
dc.identifier.doi10.1073/pnas.1001647107
dc.identifier.eissn1091-6490
dc.identifier.embargoNO
dc.identifier.filenameinventorynoIR00890
dc.identifier.issn0027-8424
dc.identifier.quartileQ1
dc.identifier.scopus2-s2.0-77950540047
dc.identifier.urihttps://doi.org/10.1073/pnas.1001647107
dc.identifier.wos413221100001
dc.keywordsγ-Secretase
dc.keywordsCancer
dc.keywordsDevelopment
dc.keywordsGamma secretase
dc.keywordsGlucagon like peptide 1
dc.keywordsNotch receptor
dc.keywordsNotch1 receptor
dc.keywordsRNA
dc.keywordsTetraspanin
dc.keywordsTetraspanin 12
dc.keywordsTSPAN33 protein
dc.keywordsTSPAN5 protein
dc.keywordsUnclassified drug
dc.keywordsCaenorhabditis elegans proteins
dc.keywordsConserved sequence
dc.keywordsDNA primers
dc.keywordsGerm cells
dc.keywordsHela cells
dc.keywordsHumans
dc.keywordsMembrane glycoproteins
dc.keywordsMembrane proteins
dc.keywordsPrecursor T-cell lymphoblastic Leukemia-lymphoma
dc.keywordsRNA interference
dc.keywordsSignal transduction
dc.language.isoeng
dc.publisherNational Academy of Sciences
dc.relation.grantnoR01CA095389
dc.relation.grantnoR01CA120196
dc.relation.grantno1287-08
dc.relation.grantno6237-08
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America
dc.relation.urihttp://cdm21054.contentdm.oclc.org/cdm/ref/collection/IR/id/887
dc.subjectMolecular biology and genetics
dc.titleA conserved tetraspanin subfamily promotes Notch signaling in Caenorhabditis elegans and in human cells
dc.typeConference Proceeding
dspace.entity.typePublication
local.contributor.kuauthorDunn, Cory David
local.publication.orgunit1College of Sciences
local.publication.orgunit2Department of Molecular Biology and Genetics
relation.isOrgUnitOfPublicationaee2d329-aabe-4b58-ba67-09dbf8575547
relation.isOrgUnitOfPublication.latestForDiscoveryaee2d329-aabe-4b58-ba67-09dbf8575547
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