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dc.contributor.authorMartin, Seamus
dc.date.accessioned2019-10-09T13:42:58Z
dc.date.available2019-10-09T13:42:58Z
dc.date.created2018en
dc.date.issued2018
dc.date.submitted2018en
dc.identifier.citationOikonomidi, I., Burbridge, E., Cavadas, M., Sullivan, G., Collis, B., Naegele, H., Clancy, D., Brezinova, J., Hu, T., Bileck, A., Gerner, C., Bolado, A., von Kriegsheim, A., Martin, S.J., Steinberg, F., Strisovsky, K., Adrain, C. ITap, a novel irhom interactor, controls TNF secretion by policing the stability of iRhom/TACE, eLife, 2018, 7en
dc.identifier.otherY
dc.identifier.urihttps://elifesciences.org/articles/35032
dc.identifier.urihttp://hdl.handle.net/2262/89663
dc.descriptionPUBLISHEDen
dc.description.abstractThe apical inflammatory cytokine TNF regulates numerous important biological processes including inflammation and cell death, and drives inflammatory diseases. TNF secretion requires TACE (also called ADAM17), which cleaves TNF from its transmembrane tether. The trafficking of TACE to the cell surface, and stimulation of its proteolytic activity, depends on membrane proteins, called iRhoms. To delineate how the TNF/TACE/iRhom axis is regulated, we performed an immunoprecipitation/mass spectrometry screen to identify iRhom-binding proteins. This identified a novel protein, that we name iTAP (iRhom Tail-Associated Protein) that binds to iRhoms, enhancing the cell surface stability of iRhoms and TACE, preventing their degradation in lysosomes. Depleting iTAP in primary human macrophages profoundly impaired TNF production and tissues from iTAP KO mice exhibit a pronounced depletion in active TACE levels. Our work identifies iTAP as a physiological regulator of TNF signalling and a novel target for the control of inflammation.en
dc.language.isoenen
dc.publishereLife Sciences Publicationsen
dc.relation.ispartofserieseLife;
dc.relation.ispartofseries7;
dc.rightsYen
dc.subjectApical inflammatory cytokine TNFen
dc.subjectInflammatory diseasesen
dc.subjectiRhom-binding proteinen
dc.titleITap, a novel irhom interactor, controls TNF secretion by policing the stability of iRhom/TACEen
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/martinsj
dc.identifier.rssinternalid204584
dc.identifier.doihttp://dx.doi.org/10.7554/eLife.35032
dc.rights.ecaccessrightsopenAccess


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