Systems level expression correlation of Ras GTPase regulators

Background: Proteins of the ubiquitously expressed core proteome are quantitatively correlated across multiple eukaryotic species. In addition, it was found that many protein paralogues exhibit expression anticorrelation, suggesting that the total level of protein with a given functionality must be...

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Detalles Bibliográficos
Autores: Unal, E. Besray, Kiel, Christina, Benisty, Hannah, 1986-, Campbell, Andrew, Pickering, Karen, Blüthgen, Nils, Sansom, Owen J., Serrano Pubull, Luis, 1982-
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/42587
Acceso en línea:http://hdl.handle.net/10230/42587
http://dx.doi.org/10.1186/s12964-018-0256-8
Access Level:acceso abierto
Palabra clave:Ras small GTPases
Tissue expression
Gene expression network
GTPase activating proteins
Guanine nucleotide exchange factors
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spelling Systems level expression correlation of Ras GTPase regulatorsUnal, E. BesrayKiel, ChristinaBenisty, Hannah, 1986-Campbell, AndrewPickering, KarenBlüthgen, NilsSansom, Owen J.Serrano Pubull, Luis, 1982-Ras small GTPasesTissue expressionGene expression networkGTPase activating proteinsGuanine nucleotide exchange factorsBackground: Proteins of the ubiquitously expressed core proteome are quantitatively correlated across multiple eukaryotic species. In addition, it was found that many protein paralogues exhibit expression anticorrelation, suggesting that the total level of protein with a given functionality must be kept constant. Methods: We performed Spearman’s rank correlation analyses of gene expression levels for the RAS GTPase subfamily and their regulatory GEF and GAP proteins across tissues and across individuals for each tissue. A large set of published data for normal tissues from a wide range of species, human cancer tissues and human cell lines was analysed. Results: We show that although the multidomain regulatory proteins of Ras GTPases exhibit considerable tissue and individual gene expression variability, their total amounts are balanced in normal tissues. In a given tissue, the sum of activating (GEFs) and deactivating (GAPs) domains of Ras GTPases can vary considerably, but each person has balanced GEF and GAP levels. This balance is impaired in cell lines and in cancer tissues for some individuals. Conclusions: Our results are relevant for critical considerations of knock out experiments, where functionally related homologs may compensate for the down regulation of a protein.This work was funded by the EU (PRIMES under grant agreement number FP7-HEALTH-F4- 2011-278568). This work was supported by the Spanish Ministerio de Economía y Competitividad, Plan Nacional BIO2012-39754 and Plan Estatal BFU2015-63571 and the European Fund for Regional Development. We acknowledge support of the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) to the EMBL partnership, to the Spanish Ministry of Economy and Competitiveness (MEC) ‘Centro de Excelencia Severo Ochoa’ and to the CERCA Programme / Generalitat de Catalunya.BioMed Central201920192018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/42587http://dx.doi.org/10.1186/s12964-018-0256-8reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésCell Communication and Signaling. 2018;16(1):46info:eu-repo/grantAgreement/EC/FP7/278568info:eu-repo/grantAgreement/ES/2PN/BIO2012-39754info:eu-repo/grantAgreement/ES/1PE/BFU2015-63571© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were madehttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/425872026-06-12T07:21:37Z
dc.title.none.fl_str_mv Systems level expression correlation of Ras GTPase regulators
title Systems level expression correlation of Ras GTPase regulators
spellingShingle Systems level expression correlation of Ras GTPase regulators
Unal, E. Besray
Ras small GTPases
Tissue expression
Gene expression network
GTPase activating proteins
Guanine nucleotide exchange factors
title_short Systems level expression correlation of Ras GTPase regulators
title_full Systems level expression correlation of Ras GTPase regulators
title_fullStr Systems level expression correlation of Ras GTPase regulators
title_full_unstemmed Systems level expression correlation of Ras GTPase regulators
title_sort Systems level expression correlation of Ras GTPase regulators
dc.creator.none.fl_str_mv Unal, E. Besray
Kiel, Christina
Benisty, Hannah, 1986-
Campbell, Andrew
Pickering, Karen
Blüthgen, Nils
Sansom, Owen J.
Serrano Pubull, Luis, 1982-
author Unal, E. Besray
author_facet Unal, E. Besray
Kiel, Christina
Benisty, Hannah, 1986-
Campbell, Andrew
Pickering, Karen
Blüthgen, Nils
Sansom, Owen J.
Serrano Pubull, Luis, 1982-
author_role author
author2 Kiel, Christina
Benisty, Hannah, 1986-
Campbell, Andrew
Pickering, Karen
Blüthgen, Nils
Sansom, Owen J.
Serrano Pubull, Luis, 1982-
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Ras small GTPases
Tissue expression
Gene expression network
GTPase activating proteins
Guanine nucleotide exchange factors
topic Ras small GTPases
Tissue expression
Gene expression network
GTPase activating proteins
Guanine nucleotide exchange factors
description Background: Proteins of the ubiquitously expressed core proteome are quantitatively correlated across multiple eukaryotic species. In addition, it was found that many protein paralogues exhibit expression anticorrelation, suggesting that the total level of protein with a given functionality must be kept constant. Methods: We performed Spearman’s rank correlation analyses of gene expression levels for the RAS GTPase subfamily and their regulatory GEF and GAP proteins across tissues and across individuals for each tissue. A large set of published data for normal tissues from a wide range of species, human cancer tissues and human cell lines was analysed. Results: We show that although the multidomain regulatory proteins of Ras GTPases exhibit considerable tissue and individual gene expression variability, their total amounts are balanced in normal tissues. In a given tissue, the sum of activating (GEFs) and deactivating (GAPs) domains of Ras GTPases can vary considerably, but each person has balanced GEF and GAP levels. This balance is impaired in cell lines and in cancer tissues for some individuals. Conclusions: Our results are relevant for critical considerations of knock out experiments, where functionally related homologs may compensate for the down regulation of a protein.
publishDate 2018
dc.date.none.fl_str_mv 2018
2019
2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/42587
http://dx.doi.org/10.1186/s12964-018-0256-8
url http://hdl.handle.net/10230/42587
http://dx.doi.org/10.1186/s12964-018-0256-8
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Cell Communication and Signaling. 2018;16(1):46
info:eu-repo/grantAgreement/EC/FP7/278568
info:eu-repo/grantAgreement/ES/2PN/BIO2012-39754
info:eu-repo/grantAgreement/ES/1PE/BFU2015-63571
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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