Loss of VRK1 alters the nuclear phosphoproteome in the DNA damage response to doxorubicin

Dynamic chromatin remodeling requires regulatory mechanisms for its adaptation to different nuclear function, which are likely to be mediated by signaling proteins. In this context, VRK1 is a nuclear Ser-Thr kinase that regulates pathways associated with transcription, replication, recombination, an...

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Autores: Navarro Carrasco, Elena, Campos Díaz, Aurora, Monte-Serrano, Eva, Rolfs, Frank, Goeij-de Haas, Richard de, Pham, Thang V., Piersma, Sander R., Jiménez, Connie R., Lazo, Pedro A.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/364809
Acceso en línea:http://hdl.handle.net/10261/364809
Access Level:acceso abierto
Palabra clave:VRK1
Phosphoproteomics
Chromatin
Nuclear proteins
DNA damage
DoxorubicinCancer
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network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Loss of VRK1 alters the nuclear phosphoproteome in the DNA damage response to doxorubicin
title Loss of VRK1 alters the nuclear phosphoproteome in the DNA damage response to doxorubicin
spellingShingle Loss of VRK1 alters the nuclear phosphoproteome in the DNA damage response to doxorubicin
Navarro Carrasco, Elena
VRK1
Phosphoproteomics
Chromatin
Nuclear proteins
DNA damage
DoxorubicinCancer
title_short Loss of VRK1 alters the nuclear phosphoproteome in the DNA damage response to doxorubicin
title_full Loss of VRK1 alters the nuclear phosphoproteome in the DNA damage response to doxorubicin
title_fullStr Loss of VRK1 alters the nuclear phosphoproteome in the DNA damage response to doxorubicin
title_full_unstemmed Loss of VRK1 alters the nuclear phosphoproteome in the DNA damage response to doxorubicin
title_sort Loss of VRK1 alters the nuclear phosphoproteome in the DNA damage response to doxorubicin
dc.creator.none.fl_str_mv Navarro Carrasco, Elena
Campos Díaz, Aurora
Monte-Serrano, Eva
Rolfs, Frank
Goeij-de Haas, Richard de
Pham, Thang V.
Piersma, Sander R.
Jiménez, Connie R.
Lazo, Pedro A.
author Navarro Carrasco, Elena
author_facet Navarro Carrasco, Elena
Campos Díaz, Aurora
Monte-Serrano, Eva
Rolfs, Frank
Goeij-de Haas, Richard de
Pham, Thang V.
Piersma, Sander R.
Jiménez, Connie R.
Lazo, Pedro A.
author_role author
author2 Campos Díaz, Aurora
Monte-Serrano, Eva
Rolfs, Frank
Goeij-de Haas, Richard de
Pham, Thang V.
Piersma, Sander R.
Jiménez, Connie R.
Lazo, Pedro A.
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia, Innovación y Universidades (España)
Agencia Estatal de Investigación (España)
Ministerio de Ciencia e Innovación (España)
Junta de Castilla y León
European Commission
EMBO
Ministerio de Universidades (España)
Netherlands Organization for Scientific Research
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv VRK1
Phosphoproteomics
Chromatin
Nuclear proteins
DNA damage
DoxorubicinCancer
topic VRK1
Phosphoproteomics
Chromatin
Nuclear proteins
DNA damage
DoxorubicinCancer
description Dynamic chromatin remodeling requires regulatory mechanisms for its adaptation to different nuclear function, which are likely to be mediated by signaling proteins. In this context, VRK1 is a nuclear Ser-Thr kinase that regulates pathways associated with transcription, replication, recombination, and DNA repair. Therefore, VRK1 is a potential regulatory, or coordinator, molecule in these processes. In this work we studied the effect that VRK1 depletion has on the basal nuclear and chromatin phosphoproteome, and their associated pathways. VRK1 depletion caused an alteration in the pattern of the nuclear phosphoproteome, which is mainly associated with nucleoproteins, ribonucleoproteins, RNA splicing and processing. Next, it was determined the changes in proteins associated with DNA damage that was induced by doxorubicin treatment. Doxorubicin alters the nuclear phosphoproteome affecting proteins implicated in DDR, including DSB repair proteins NBN and 53BP1, cellular response to stress and chromatin organization proteins. In VRK1-depleted cells, the effect of doxorubicin on protein phosphorylation was reverted to basal levels. The nuclear phosphoproteome patterns induced by doxorubicin are altered by VRK1 depletion, and is enriched in histone modification proteins and chromatin associated proteins. These results indicate that VRK1 plays a major role in processes requiring chromatin remodeling in its adaptation to different biological contexts.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024
2024
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/10261/364809
url http://hdl.handle.net/10261/364809
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-105610RB-I00
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2022-139598OB-I00
info:eu-repo/grantAgreement/AEI//RED2018-102801-T
The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.1016/j.cbi.2024.110908
https://doi.org/10.1016/j.cbi.2024.110908
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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dc.format.none.fl_str_mv application/pdf
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
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spelling Loss of VRK1 alters the nuclear phosphoproteome in the DNA damage response to doxorubicinNavarro Carrasco, ElenaCampos Díaz, AuroraMonte-Serrano, EvaRolfs, FrankGoeij-de Haas, Richard dePham, Thang V.Piersma, Sander R.Jiménez, Connie R.Lazo, Pedro A.VRK1PhosphoproteomicsChromatinNuclear proteinsDNA damageDoxorubicinCancerDynamic chromatin remodeling requires regulatory mechanisms for its adaptation to different nuclear function, which are likely to be mediated by signaling proteins. In this context, VRK1 is a nuclear Ser-Thr kinase that regulates pathways associated with transcription, replication, recombination, and DNA repair. Therefore, VRK1 is a potential regulatory, or coordinator, molecule in these processes. In this work we studied the effect that VRK1 depletion has on the basal nuclear and chromatin phosphoproteome, and their associated pathways. VRK1 depletion caused an alteration in the pattern of the nuclear phosphoproteome, which is mainly associated with nucleoproteins, ribonucleoproteins, RNA splicing and processing. Next, it was determined the changes in proteins associated with DNA damage that was induced by doxorubicin treatment. Doxorubicin alters the nuclear phosphoproteome affecting proteins implicated in DDR, including DSB repair proteins NBN and 53BP1, cellular response to stress and chromatin organization proteins. In VRK1-depleted cells, the effect of doxorubicin on protein phosphorylation was reverted to basal levels. The nuclear phosphoproteome patterns induced by doxorubicin are altered by VRK1 depletion, and is enriched in histone modification proteins and chromatin associated proteins. These results indicate that VRK1 plays a major role in processes requiring chromatin remodeling in its adaptation to different biological contexts.This research was funded by grants to P. A. L. from Agencia Estatal de Investigación (https://doi.org/10.13039/501100011033-Ministerio) de Ciencia e Innovación-FEDER “Una manera de hacer Europa” (PID2019-105610RB-I00, PID2022-139598OB-I00, RED2018-102801-T), Consejería de Educación de la Junta de Castilla y León-FEDER (CSI264P20, CLC-2017-01). E. N–C was funded by Agencia Estatal de Investigación-MINECO predoctoral fellowship (BES-2017-080543) and EMBO Scientific Exchange Grant ( 9289). A. C-D was funded by a predoctoral contract from Ministerio de Universidades (FPU20/02978 ). E. M-S. was funded by a predoctoral fellowship (CSI004-18) from Consejería de Educación-Junta de Castilla y León-Fondo Social Europeo. Cancer Center Amsterdam and Netherlands Organization for Scientific Research (NWOMiddelgroot project number 91116017) are acknowledged for support of the mass spectrometry infrastructure and Surfsara for computing infrastructure (reference e-infra180166)”.Peer reviewedElsevierMinisterio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)Ministerio de Ciencia e Innovación (España)Junta de Castilla y LeónEuropean CommissionEMBOMinisterio de Universidades (España)Netherlands Organization for Scientific ResearchConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202420242024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/364809reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-105610RB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2022-139598OB-I00info:eu-repo/grantAgreement/AEI//RED2018-102801-TThe underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.1016/j.cbi.2024.110908https://doi.org/10.1016/j.cbi.2024.110908Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3648092026-05-22T06:33:51Z
score 15.811543

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