The dynamics of ubiquitination and its role within the proteome of extracellular vesicles

The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD067810. Any additional requests can be directed to the corresponding author.

Detalles Bibliográficos
Autores: Morales-Tarré, Orlando, Popa-Navarro, Xitlally, Paradela, Alberto, Hernández-Ortiz, Magdalena, Arrieta, Oscar, Corrales, Fernando J., Encarnación-Guevara, Sergio
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2026
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/416828
Acceso en línea:http://hdl.handle.net/10261/416828
https://api.elsevier.com/content/abstract/scopus_id/105022118600
Access Level:acceso abierto
Palabra clave:BEAS-2B
Exosomes
Extracellular vesicles
Mass spectrometry
Microvesicles
Proteomics
Ubiquitination
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spelling The dynamics of ubiquitination and its role within the proteome of extracellular vesiclesMorales-Tarré, OrlandoPopa-Navarro, XitlallyParadela, AlbertoHernández-Ortiz, MagdalenaArrieta, OscarCorrales, Fernando J.Encarnación-Guevara, SergioBEAS-2BExosomesExtracellular vesiclesMass spectrometryMicrovesiclesProteomicsUbiquitinationThe mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD067810. Any additional requests can be directed to the corresponding author.Ubiquitination is a multifaceted post-translational modification that plays a crucial role in regulating the degradation of unnecessary cellular proteins and is involved in various cellular processes, including protein export via extracellular vesicles. We investigate how alterations in the intracellular levels of ubiquitinated proteins affect vesicle protein content in BEAS-2B cells. We increased the intracellular levels of ubiquitinated proteins by inhibiting proteasomal degradation with MG-132 and by blocking deubiquitinating enzymes using PR-619. Using centrifugation and ultracentrifugation, were isolate various vesicle types, specifically the largest vesicles (enriched in plasma membrane-derived microvesicles) and the smallest vesicles (enriched in endosomal exosomes). High-resolution mass spectrometry-based proteomics was utilized to quantify their protein content. The content of extracellular vesicles changed in response to both treatments, reflecting cellular changes and the export of stress signals. The increase in intracellular levels of ubiquitinated proteins induced metabolic stress in the cells, generally leading to a reduction in protein translation, an enhanced response to oxidative stress, changes in membrane transport, and alterations in cell-microenvironment interactions. The modifications observed in the vesicular proteome suggest that ubiquitination plays a significant role in regulating protein export. This regulation can be mastered for diagnostic purposes and for describing cells and tissues through liquid biopsies. SIGNIFICANCE: Ubiquitination is one of the most abundant post-translational modifications in cells, and its role, beyond marking proteins for degradation, is not fully understood. Characterizing the effect of this modification on protein export to extracellular vesicles can shed light on how a cell selects its contents to influence its microenvironment, send signals to distant tissues, or interact with the immune system. This is particularly relevant in the context of pathologies such as cancer, which hijacks the cellular vesicle-producing machinery and adapts it to its needs to influence the remodeling of its surroundings. Understanding how a cell regulates the specific contents of its vesicles may point the way toward the development of treatments or superior diagnostic and classification tools.This manuscript was funded by the grant DGAPA-PAPIIT (IN213216) to Sergio Encarnación-Guevara.Peer reviewedElsevierParadela, Alberto [0000-0001-6837-7056]Corrales, Fernando J. [0000-0002-0231-5159]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202620262026info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/416828https://api.elsevier.com/content/abstract/scopus_id/105022118600reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésJournal of proteomicsapplication/pdfhttps://doi.org/10.1016/j.jprot.2025.105566Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/4168282026-05-22T06:33:51Z
dc.title.none.fl_str_mv The dynamics of ubiquitination and its role within the proteome of extracellular vesicles
title The dynamics of ubiquitination and its role within the proteome of extracellular vesicles
spellingShingle The dynamics of ubiquitination and its role within the proteome of extracellular vesicles
Morales-Tarré, Orlando
BEAS-2B
Exosomes
Extracellular vesicles
Mass spectrometry
Microvesicles
Proteomics
Ubiquitination
title_short The dynamics of ubiquitination and its role within the proteome of extracellular vesicles
title_full The dynamics of ubiquitination and its role within the proteome of extracellular vesicles
title_fullStr The dynamics of ubiquitination and its role within the proteome of extracellular vesicles
title_full_unstemmed The dynamics of ubiquitination and its role within the proteome of extracellular vesicles
title_sort The dynamics of ubiquitination and its role within the proteome of extracellular vesicles
dc.creator.none.fl_str_mv Morales-Tarré, Orlando
Popa-Navarro, Xitlally
Paradela, Alberto
Hernández-Ortiz, Magdalena
Arrieta, Oscar
Corrales, Fernando J.
Encarnación-Guevara, Sergio
author Morales-Tarré, Orlando
author_facet Morales-Tarré, Orlando
Popa-Navarro, Xitlally
Paradela, Alberto
Hernández-Ortiz, Magdalena
Arrieta, Oscar
Corrales, Fernando J.
Encarnación-Guevara, Sergio
author_role author
author2 Popa-Navarro, Xitlally
Paradela, Alberto
Hernández-Ortiz, Magdalena
Arrieta, Oscar
Corrales, Fernando J.
Encarnación-Guevara, Sergio
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Paradela, Alberto [0000-0001-6837-7056]
Corrales, Fernando J. [0000-0002-0231-5159]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv BEAS-2B
Exosomes
Extracellular vesicles
Mass spectrometry
Microvesicles
Proteomics
Ubiquitination
topic BEAS-2B
Exosomes
Extracellular vesicles
Mass spectrometry
Microvesicles
Proteomics
Ubiquitination
description The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD067810. Any additional requests can be directed to the corresponding author.
publishDate 2026
dc.date.none.fl_str_mv 2026
2026
2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/416828
https://api.elsevier.com/content/abstract/scopus_id/105022118600
url http://hdl.handle.net/10261/416828
https://api.elsevier.com/content/abstract/scopus_id/105022118600
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Journal of proteomics
application/pdf
https://doi.org/10.1016/j.jprot.2025.105566

dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
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