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Quantitative proteomics screen identifies a substrate repertoire of rhomboid protease RHBDL2 in human cells and implicates it in epithelial homeostasis

2017-08-04Journal article Open access
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dc.contributor.authorJohnson, Nicholas
dc.contributor.authorBřezinová, Jana
dc.contributor.authorStephens, Elaine
dc.contributor.authorBurbridge, Emma
dc.contributor.authorFreeman, Matthew
dc.contributor.authorAdrain, Colin
dc.contributor.authorStrisovsky, Kvido
dc.date.accessioned2017-08-08T10:49:07Z
dc.date.available2017-08-08T10:49:07Z
dc.date.issued2017-08-04
dc.descriptionThis deposit is composed by the main article plus the supplementary materials of the publication.pt_PT
dc.description.abstractRhomboids are intramembrane serine proteases conserved in all kingdoms of life. They regulate epidermal growth factor receptor signalling in Drosophila by releasing signalling ligands from their transmembrane tethers. Their functions in mammals are poorly understood, in part because of the lack of endogenous substrates identified thus far. We used a quantitative proteomics approach to investigate the substrate repertoire of rhomboid protease RHBDL2 in human cells. We reveal a range of novel substrates that are specifically cleaved by RHBDL2, including the interleukin-6 receptor (IL6R), cell surface protease inhibitor Spint-1, the collagen receptor tyrosine kinase DDR1, N-Cadherin, CLCP1/DCBLD2, KIRREL, BCAM and others. We further demonstrate that these substrates can be shed by endogenously expressed RHBDL2 and that a subset of them is resistant to shedding by cell surface metalloproteases. The expression profiles and identity of the substrates implicate RHBDL2 in physiological or pathological processes affecting epithelial homeostasis.pt_PT
dc.description.sponsorshipAcademy of Sciences of the Czech Republic grant: (Purkyne Fellowship); EMBO grant: (Installation Grant no. 2329); Ministry of Education, Youth and Sports of the Czech Republic grants: (projects no. LK11206 and LO1302); Marie Curie Career Integration grant: (project no. 304154); National Subvention for Development of Research Organisations grant: (RVO: 61388963); Institute of Organic Chemistry and Biochemistry; Fundação Calouste Gulbenkian; Worldwide Cancer Research grant: (14–1289); Marie Curie Career Integration grant: (project no. 618769); Fundação para a Ciência e Tecnologica (FCT, PTDC/BEX-BCM/3015/2014); European Crohn’s and Colitis organization (ECCO); COST BM1406; Wellcome Trust grant: (101035/Z/13/Z); Medical Research Council grant: (programme number MC_U105178780).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJohnson, N. et al. Quantitative proteomics screen identifies a substrate repertoire of rhomboid protease RHBDL2 in human cells and implicates it in epithelial homeostasis. Sci Rep 7, 7283 (2017).pt_PT
dc.identifier.doi10.1038/s41598-017-07556-3pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.7/781
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherNature Publishing Grouppt_PT
dc.relationEMBO 2329pt_PT
dc.relationLK11206pt_PT
dc.relationLO1302pt_PT
dc.relationSubstrate specificity, mechanism and biological roles of rhomboid intramembrane proteases.
dc.relationWorldwide Cancer Research (14–1289)pt_PT
dc.relationIntramembrane Proteases, their Inactive cognates, and Disease
dc.relationCOST BM1406pt_PT
dc.relationMC_U105178780pt_PT
dc.relation.publisherversionhttps://www.nature.com/articles/s41598-017-07556-3pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectProteasespt_PT
dc.subjectSecretionpt_PT
dc.titleQuantitative proteomics screen identifies a substrate repertoire of rhomboid protease RHBDL2 in human cells and implicates it in epithelial homeostasispt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleSubstrate specificity, mechanism and biological roles of rhomboid intramembrane proteases.
oaire.awardTitleIntramembrane Proteases, their Inactive cognates, and Disease
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/304154/EU
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/618769/EU
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FBEX-BCM%2F3015%2F2014/PT
oaire.awardURIinfo:eu-repo/grantAgreement/WT/Molecules, Genes and Cells/101035
oaire.citation.endPage13pt_PT
oaire.citation.issue1pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titleScientific Reportspt_PT
oaire.citation.volume7pt_PT
oaire.fundingStreamFP7
oaire.fundingStreamFP7
oaire.fundingStream3599-PPCDT
oaire.fundingStreamMolecules, Genes and Cells
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/100010269
project.funder.nameEuropean Commission
project.funder.nameEuropean Commission
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameWellcome Trust
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication9b0cd3bb-c083-4398-86e8-9e5c7a3d0524
relation.isProjectOfPublicationd0670159-bb7c-4928-8332-8f581a65aac6
relation.isProjectOfPublicationbf50df3f-7870-4574-88e6-0a346a36c105
relation.isProjectOfPublication239e1d45-5451-4cef-8e16-48797afd54ba
relation.isProjectOfPublication.latestForDiscovery9b0cd3bb-c083-4398-86e8-9e5c7a3d0524

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