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

Bibliographic Details
Main Author: Johnson, Nicholas
Publication Date: 2017
Other Authors: Březinová, Jana, Stephens, Elaine, Burbridge, Emma, Freeman, Matthew, Adrain, Colin, Strisovsky, Kvido
Format: Article
Language: eng
Source: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Download full: http://hdl.handle.net/10400.7/781
Summary: This deposit is composed by the main article plus the supplementary materials of the publication.
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spelling Quantitative proteomics screen identifies a substrate repertoire of rhomboid protease RHBDL2 in human cells and implicates it in epithelial homeostasisProteasesSecretionThis deposit is composed by the main article plus the supplementary materials of the publication.Rhomboids 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.Academy 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).Nature Publishing GroupARCAJohnson, NicholasBřezinová, JanaStephens, ElaineBurbridge, EmmaFreeman, MatthewAdrain, ColinStrisovsky, Kvido2017-08-08T10:49:07Z2017-08-042017-08-04T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfapplication/pdfhttp://hdl.handle.net/10400.7/781engJohnson, 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).10.1038/s41598-017-07556-3info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2022-11-29T14:35:11Zoai:arca.igc.gulbenkian.pt:10400.7/781Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T16:12:00.464762Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Quantitative proteomics screen identifies a substrate repertoire of rhomboid protease RHBDL2 in human cells and implicates it in epithelial homeostasis
title Quantitative proteomics screen identifies a substrate repertoire of rhomboid protease RHBDL2 in human cells and implicates it in epithelial homeostasis
spellingShingle Quantitative proteomics screen identifies a substrate repertoire of rhomboid protease RHBDL2 in human cells and implicates it in epithelial homeostasis
Johnson, Nicholas
Proteases
Secretion
title_short Quantitative proteomics screen identifies a substrate repertoire of rhomboid protease RHBDL2 in human cells and implicates it in epithelial homeostasis
title_full Quantitative proteomics screen identifies a substrate repertoire of rhomboid protease RHBDL2 in human cells and implicates it in epithelial homeostasis
title_fullStr Quantitative proteomics screen identifies a substrate repertoire of rhomboid protease RHBDL2 in human cells and implicates it in epithelial homeostasis
title_full_unstemmed Quantitative proteomics screen identifies a substrate repertoire of rhomboid protease RHBDL2 in human cells and implicates it in epithelial homeostasis
title_sort Quantitative proteomics screen identifies a substrate repertoire of rhomboid protease RHBDL2 in human cells and implicates it in epithelial homeostasis
author Johnson, Nicholas
author_facet Johnson, Nicholas
Březinová, Jana
Stephens, Elaine
Burbridge, Emma
Freeman, Matthew
Adrain, Colin
Strisovsky, Kvido
author_role author
author2 Březinová, Jana
Stephens, Elaine
Burbridge, Emma
Freeman, Matthew
Adrain, Colin
Strisovsky, Kvido
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv ARCA
dc.contributor.author.fl_str_mv Johnson, Nicholas
Březinová, Jana
Stephens, Elaine
Burbridge, Emma
Freeman, Matthew
Adrain, Colin
Strisovsky, Kvido
dc.subject.por.fl_str_mv Proteases
Secretion
topic Proteases
Secretion
description This deposit is composed by the main article plus the supplementary materials of the publication.
publishDate 2017
dc.date.none.fl_str_mv 2017-08-08T10:49:07Z
2017-08-04
2017-08-04T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
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dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.7/781
url http://hdl.handle.net/10400.7/781
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Johnson, 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).
10.1038/s41598-017-07556-3
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
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dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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