VRK1 regulates Cajal body dynamics and protects coilin from proteasomal degradation in cell cycle

Cajal bodies (CBs) are nuclear organelles associated with ribonucleoprotein functions and RNA maturation. CBs are assembled on coilin, its main scaffold protein, in a cell cycle dependent manner. The Ser-Thr VRK1 (vaccinia-related kinase 1) kinase, whose activity is also cell cycle regulated, intera...

Descripción completa

Detalles Bibliográficos
Autores: Cantarero, Lara, Sanz-García, Marta, Vinograd-Byk, Hadar, Renbaum, Paul, Levy-Lahad, Ephrat, Lazo, Pedro A.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/117336
Acceso en línea:http://hdl.handle.net/10261/117336
Access Level:acceso abierto
Palabra clave:VRK1
Cajal bodies
Coilin
Phosphorylation
Cell cycle
id ES_0cbb28f2cc881bf95cbefa5a4d2b8e28
oai_identifier_str oai:digital.csic.es:10261/117336
network_acronym_str ES
network_name_str España
repository_id_str
spelling VRK1 regulates Cajal body dynamics and protects coilin from proteasomal degradation in cell cycleCantarero, LaraSanz-García, MartaVinograd-Byk, HadarRenbaum, PaulLevy-Lahad, EphratLazo, Pedro A.VRK1Cajal bodiesCoilinPhosphorylationCell cycleCajal bodies (CBs) are nuclear organelles associated with ribonucleoprotein functions and RNA maturation. CBs are assembled on coilin, its main scaffold protein, in a cell cycle dependent manner. The Ser-Thr VRK1 (vaccinia-related kinase 1) kinase, whose activity is also cell cycle regulated, interacts with and phosphorylates coilin regulating assembly of CBs. Coilin phosphorylation is not necessary for its interaction with VRK1, but it occurs in mitosis and regulates coilin stability. Knockdown of VRK1 or VRK1 inactivation by serum deprivation causes a loss of coilin phosphorylation in Ser184 and of CBs formation, which are rescued with an active VRK1, but not by kinase-dead VRK1. The phosphorylation of coilin in Ser184 occurs during mitosis before assembly of CBs. Loss of coilin phosphorylation results in disintegration of CBs, and of coilin degradation that is prevented by proteasome inhibitors. After depletion of VRK1, coilin is ubiquitinated in nuclei, which is partly mediated by mdm2, but its proteasomal degradation occurs in cytosol and is prevented by blocking its nuclear export. We conclude that VRK1 is a novel regulator of CBs dynamics and stability in cell cycle by protecting coilin from ubiquitination and degradation in the proteasome, and propose a model of CB dynamics.L. C. and M. S-G. were funded by JAE-CSIC-Fondo Social Europeo fellowships. This work was supported by grants from Ministerio de Ciencia e Innovación (SAF2010-14935), Ministerio de Economía y Competitividad (SAF2013-44810R, SAF2014-57791-REDC), and Junta de Castilla y León-Consejería de Educación (CSI002U14) to P.A.L;and grant (702/13) from the Israel Science Foundation to P.R. and E.L.L.Peer reviewedNature Publishing GroupMinisterio de Economía y Competitividad (España)Consejo Superior de Investigaciones Científicas (España)Junta de Castilla y LeónMinisterio de Ciencia e Innovación (España)European CommissionIsrael Science FoundationConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]201520152015info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/117336reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2013-44810-Rinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2014-57791-REDCSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1173362026-05-22T06:33:51Z
dc.title.none.fl_str_mv VRK1 regulates Cajal body dynamics and protects coilin from proteasomal degradation in cell cycle
title VRK1 regulates Cajal body dynamics and protects coilin from proteasomal degradation in cell cycle
spellingShingle VRK1 regulates Cajal body dynamics and protects coilin from proteasomal degradation in cell cycle
Cantarero, Lara
VRK1
Cajal bodies
Coilin
Phosphorylation
Cell cycle
title_short VRK1 regulates Cajal body dynamics and protects coilin from proteasomal degradation in cell cycle
title_full VRK1 regulates Cajal body dynamics and protects coilin from proteasomal degradation in cell cycle
title_fullStr VRK1 regulates Cajal body dynamics and protects coilin from proteasomal degradation in cell cycle
title_full_unstemmed VRK1 regulates Cajal body dynamics and protects coilin from proteasomal degradation in cell cycle
title_sort VRK1 regulates Cajal body dynamics and protects coilin from proteasomal degradation in cell cycle
dc.creator.none.fl_str_mv Cantarero, Lara
Sanz-García, Marta
Vinograd-Byk, Hadar
Renbaum, Paul
Levy-Lahad, Ephrat
Lazo, Pedro A.
author Cantarero, Lara
author_facet Cantarero, Lara
Sanz-García, Marta
Vinograd-Byk, Hadar
Renbaum, Paul
Levy-Lahad, Ephrat
Lazo, Pedro A.
author_role author
author2 Sanz-García, Marta
Vinograd-Byk, Hadar
Renbaum, Paul
Levy-Lahad, Ephrat
Lazo, Pedro A.
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Consejo Superior de Investigaciones Científicas (España)
Junta de Castilla y León
Ministerio de Ciencia e Innovación (España)
European Commission
Israel Science Foundation
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv VRK1
Cajal bodies
Coilin
Phosphorylation
Cell cycle
topic VRK1
Cajal bodies
Coilin
Phosphorylation
Cell cycle
description Cajal bodies (CBs) are nuclear organelles associated with ribonucleoprotein functions and RNA maturation. CBs are assembled on coilin, its main scaffold protein, in a cell cycle dependent manner. The Ser-Thr VRK1 (vaccinia-related kinase 1) kinase, whose activity is also cell cycle regulated, interacts with and phosphorylates coilin regulating assembly of CBs. Coilin phosphorylation is not necessary for its interaction with VRK1, but it occurs in mitosis and regulates coilin stability. Knockdown of VRK1 or VRK1 inactivation by serum deprivation causes a loss of coilin phosphorylation in Ser184 and of CBs formation, which are rescued with an active VRK1, but not by kinase-dead VRK1. The phosphorylation of coilin in Ser184 occurs during mitosis before assembly of CBs. Loss of coilin phosphorylation results in disintegration of CBs, and of coilin degradation that is prevented by proteasome inhibitors. After depletion of VRK1, coilin is ubiquitinated in nuclei, which is partly mediated by mdm2, but its proteasomal degradation occurs in cytosol and is prevented by blocking its nuclear export. We conclude that VRK1 is a novel regulator of CBs dynamics and stability in cell cycle by protecting coilin from ubiquitination and degradation in the proteasome, and propose a model of CB dynamics.
publishDate 2015
dc.date.none.fl_str_mv 2015
2015
2015
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/10261/117336
url http://hdl.handle.net/10261/117336
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#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2013-44810-R
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2014-57791-REDC
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
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
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869403300658413568
score 15,808905

Similares en LA Referencia