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dc.contributor.authorMéndez-Pertuz, Marinela
dc.contributor.authorMartinez Rodriguez, Paula 
dc.contributor.authorBlanco Aparicio, Carmen 
dc.contributor.authorGomez Casero, Elena 
dc.contributor.authorBelen García, Ana
dc.contributor.authorMartinez Torrecuadrada, Jorge Luis 
dc.contributor.authorPalafox, Marta
dc.contributor.authorCortés, Javier
dc.contributor.authorSerra, Violeta
dc.contributor.authorPastor Fernández, Joaquín 
dc.contributor.authorBlasco , MA 
dc.date.accessioned2018-12-13T12:00:35Z
dc.date.available2018-12-13T12:00:35Z
dc.date.issued2017
dc.identifier.citationNat Commun. 2017; 8:1278.es_ES
dc.identifier.issn2041-1723es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/6847
dc.description.abstractTelomeres and the insulin/PI3K pathway are considered hallmarks of aging and cancer. Here, we describe a role for PI3K/AKT in the regulation of TRF1, an essential component of the shelterin complex. PI3K and AKT chemical inhibitors reduce TRF1 telomeric foci and lead to increased telomeric DNA damage and fragility. We identify the PI3Kα isoform as responsible for this TRF1 inhibition. TRF1 is phosphorylated at different residues by AKT and these modifications regulate TRF1 protein stability and TRF1 binding to telomeric DNA in vitro and are important for in vivo TRF1 telomere location and cell viability. Patient-derived breast cancer PDX mouse models that effectively respond to a PI3Kα specific inhibitor, BYL719, show decreased TRF1 levels and increased DNA damage. These findings functionally connect two of the major pathways for cancer and aging, telomeres and the PI3K pathway, and pinpoint PI3K and AKT as novel targets for chemical modulation of telomere protection.es_ES
dc.description.sponsorshipWe are indebted to D. Megias for microscopy analysis, to D. Calvo for protein purification as well as to J. Muñoz and F. García for LC/MS/MS analysis. The research was funded by project SAF2013-45111-R of Societal Changes Program of the Spanish Ministry of Economics and Competitiveness (MINECO) co-financed through the European Fund of Regional Development (FEDER), Fundación Botín, Banco Santander (Santander Universities Global Division) and Worldwide Cancer Research (WCR 16-1177).es_ES
dc.language.isoenges_ES
dc.publisherNature Publishing Groupes_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.meshAging es_ES
dc.subject.meshAnimals es_ES
dc.subject.meshBreast Neoplasms es_ES
dc.subject.meshDNA Damage es_ES
dc.subject.meshHumans es_ES
dc.subject.meshMice es_ES
dc.subject.meshNeoplasm Transplantation es_ES
dc.subject.meshPhosphatidylinositol 3-Kinases es_ES
dc.subject.meshPhosphorylation es_ES
dc.subject.meshProtein Stability es_ES
dc.subject.meshProto-Oncogene Proteins c-akt es_ES
dc.subject.meshTelomere es_ES
dc.subject.meshTelomeric Repeat Binding Protein 1 es_ES
dc.subject.meshThiazoles es_ES
dc.titleModulation of telomere protection by the PI3K/AKT pathwayes_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID29097657es_ES
dc.format.volume8es_ES
dc.format.number1es_ES
dc.format.page1278es_ES
dc.identifier.doi10.1038/s41467-017-01329-2es_ES
dc.contributor.funderMinisterio de Ciencia e Innovación (España)es_ES
dc.contributor.funderFundación Marcelo Botínes_ES
dc.contributor.funderBanco Santanderes_ES
dc.contributor.funderWorldwide Cancer Researches_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn2041-1723es_ES
dc.relation.publisherversionhttps://doi.org/10.1038/s41467-017-01329-2.es_ES
dc.identifier.journalNature communicationses_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Telómeros y Telomerasaes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2013-45111-Res_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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