Show simple item record

Article

dc.creatorHerrero Ruiz, Joaquínes
dc.creatorMora Santos, María del Mares
dc.creatorGiraldez Macias, Servandoes
dc.creatorSáez Torres, Carmenes
dc.creatorRomero Portillo, Franciscoes
dc.creatorJapón Rodríguez, Miguel Ángeles
dc.date.accessioned2017-06-07T10:18:52Z
dc.date.available2017-06-07T10:18:52Z
dc.date.issued2014
dc.identifier.citationHerrero Ruiz, J., Mora Santos, M.d.M., Giraldez Macias, S., Sáez Torres, C., Romero Portillo, F. y Japón Rodríguez, M.Á. (2014). βTrCP controls the lysosome-mediated degradation of CDK1, whose accumulation correlates with tumor malignancy. Oncotarget, 5 (17), 7563-7574.
dc.identifier.issn1949-2553es
dc.identifier.urihttp://hdl.handle.net/11441/61074
dc.description.abstractn mammals, cell cycle progression is controlled by cyclin-dependent kinases, among which CDK1 plays important roles in the regulation of the G2/M transition, G1 progression and G1/S transition. CDK1 is highly regulated by its association to cyclins, phosphorylation and dephosphorylation, changes in subcellular localization, and by direct binding of CDK inhibitor proteins. CDK1 steady-state protein levels are held constant throughout the cell cycle by a coordinated regulation of protein synthesis and degradation. We show that CDK1 is ubiquitinated by the E3 ubiquitin ligase SCFβTrCP and degraded by the lysosome. Furthermore, we found that DNA damage not only triggers the stabilization of inhibitory phosphorylation sites on CDK1 and repression of CDK1 gene expression, but also regulates βTrCP-induced CDK1 degradation in a cell type-dependent manner. Specifically, treatment with the chemotherapeutic agent doxorubicin in certain cell lines provokes CDK1 degradation and induces apoptosis, whereas in others it inhibits destruction of the protein. These observations raise the possibility that different tumor types, depending on their pathogenic spectrum mutations, may display different sensitivity to βTrCP-induced CDK1 degradation after DNA damage. Finally, we found that CDK1 accumulation in patients’ tumors shows a negative correlation with βTrCP and a positive correlation with the degree of tumor malignancy.es
dc.description.sponsorshipEspaña, Ministerio de Economía y Competitividad SAF2011-30003es
dc.description.sponsorshipJunta de Andalucía, Dirección General de Investigación, Tecnología y Empresa P08- CVI-03603 and P10-CTS-6243]es
dc.formatapplication/pdfes
dc.language.isoenges
dc.publisherImpact Journalses
dc.relation.ispartofOncotarget, 5 (17), 7563-7574.
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectapoptosises
dc.subjectautophagyes
dc.subjectβTrCPes
dc.subjectcanceres
dc.titleβTrCP controls the lysosome-mediated degradation of CDK1, whose accumulation correlates with tumor malignancyes
dc.typeinfo:eu-repo/semantics/articlees
dc.type.versioninfo:eu-repo/semantics/publishedVersiones
dc.rights.accessrightsinfo:eu-repo/semantics/openAccesses
dc.contributor.affiliationUniversidad de Sevilla. Departamento de Microbiologíaes
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO/SAF2011-30003es
dc.relation.projectIDP10-CTS-6243es
dc.relation.projectIDP08- CVI-03603es
dc.relation.publisherversionhttp://dx.doi.org/10.18632/oncotarget.2274es
dc.identifier.doi10.18632/oncotarget.2274es
idus.format.extent11 p.es
dc.journaltitleOncotargetes
dc.publication.volumen5es
dc.publication.issue17es
dc.publication.initialPage7563es
dc.publication.endPage7574es
dc.contributor.funderMinisterio de Economía y Competitividad (MINECO). España
dc.contributor.funderJunta de Andalucía

FilesSizeFormatViewDescription
pub4oncotarget-05-7563.pdf3.154MbIcon   [PDF] View/Open  

This item appears in the following collection(s)

Show simple item record

Attribution-NonCommercial-NoDerivatives 4.0 Internacional
Except where otherwise noted, this item's license is described as: Attribution-NonCommercial-NoDerivatives 4.0 Internacional