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iTAP, a novel iRhom interactor, controls TNF secretion by policing the stability of iRhom/TACE

2018Journal article Open access
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dc.contributor.authorOikonomidi, Ioanna
dc.contributor.authorBurbridge, Emma
dc.contributor.authorCavadas, Miguel
dc.contributor.authorSullivan, Graeme
dc.contributor.authorCollis, Blanka
dc.contributor.authorNaegele, Heike
dc.contributor.authorClancy, Danielle
dc.contributor.authorBrezinova, Jana
dc.contributor.authorHu, Tianyi
dc.contributor.authorBileck, Andrea
dc.contributor.authorGerner, Christopher
dc.contributor.authorBolado, Alfonso
dc.contributor.authorKriegsheim, Alex Von
dc.contributor.authorMartin, Seamus J.
dc.contributor.authorSteinberg, Florian
dc.date.accessioned2019-12-09T23:43:19Z
dc.date.available2019-12-09T23:43:19Z
dc.date.issued2018
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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.7554/eLife.35032.001pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.7/912
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publishereLife Sciences Publicationspt_PT
dc.relationFundação Calouste Gulbenkian 91/BD/14pt_PT
dc.relationFCT SFRH/ BPD/117216/2016pt_PT
dc.relationScience Foundation Ireland 14/IA/2622pt_PT
dc.relationDeutsche Forschungsge- meinschaft Emmy Noether scholarship DFG STE2310/1-1pt_PT
dc.relationEuropean Molecular Biology Organization Installation Grant no. 2329pt_PT
dc.relationMinisterstvo Skolstv ́ı, Mla ́dezˇe a T?lovy ́chovy LO1302pt_PT
dc.relationEuropean Regional Develop- ment Fund CZ.2.16/3.1.00/24016pt_PT
dc.relationWorldwide Cancer Research 14-1289pt_PT
dc.relationFCT SFRH/BCC/52507/2014pt_PT
dc.relationSeventh Framework Programme Marie Curie Career Integration Grant (project no. 618769pt_PT
dc.relationFCT PTDC/BEX-BCM/3015/2014pt_PT
dc.relationEuropean Cooperation in Science and Technology BM1406pt_PT
dc.relationFCT BEX-BCM/3015/2014pt_PT
dc.relationFCT LISBOA-01-0145-FEDER- 031330pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectiTAPpt_PT
dc.subjectIRhom interactorpt_PT
dc.subjectTACEpt_PT
dc.subjectTNFpt_PT
dc.titleiTAP, a novel iRhom interactor, controls TNF secretion by policing the stability of iRhom/TACEpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage35pt_PT
oaire.citation.startPage1pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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