Mostrar el registro sencillo del ítem

dc.contributor.authorAix, Esther 
dc.contributor.authorGutierrez-Gutierrez, Oscar 
dc.contributor.authorSanchez-Ferrer, Carlota 
dc.contributor.authorAguado, Tania 
dc.contributor.authorFlores, Ignacio 
dc.date.accessioned2017-10-30T13:15:44Z
dc.date.available2017-10-30T13:15:44Z
dc.date.issued2016
dc.identifierISI:000377555500011
dc.identifier.citationJ Cell Biol. 2016; 213(5):571-83
dc.identifier.issn0021-9525
dc.identifier.urihttp://hdl.handle.net/20.500.12105/5221
dc.description.abstractThe molecular mechanisms that drive mammalian cardiomyocytes out of the cell cycle soon after birth remain largely unknown. Here, we identify telomere dysfunction as a critical physiological signal for cardiomyocyte cell-cycle arrest. We show that telomerase activity and cardiomyocyte telomere length decrease sharply in wild-type mouse hearts after birth, resulting in cardiomyocytes with dysfunctional telomeres and anaphase bridges and positive for the cell-cycle arrest protein p21. We further show that premature telomere dysfunction pushes cardiomyocytes out of the cell cycle. Cardiomyocytes from telomerase-deficient mice with dysfunctional telomeres (G3 Terc(-/-)) show precocious development of anaphase-bridge formation, p21 up-regulation, and binucleation. In line with these findings, the cardiomyocyte proliferative response after cardiac injury was lost in G3 Terc(-/-) newborns but rescued in G3 Terc(-/-)/p21(-/-) mice. These results reveal telomere dysfunction as a crucial signal for cardiomyocyte cell-cycle arrest after birth and suggest interventions to augment the regeneration capacity of mammalian hearts.
dc.description.sponsorshipE. Aix was supported by a Formation de Profesorado Universitario predoctoral fellowship from the Ministerio de Educacion. C. Sanchez - Ferrer is supported by a predoctoral fellowship from the Ministerio de Economia y Competitividad. T. Aguado is a recipient of a Fundacion Cientifica Asociacion Espanola Contra el Cancer postdoctoral fellowship. This study was supported by grants from the Ministerio de Economia y Competitividad (SAF2012-38449 to I. Flores) and the Red Tematica de Investigation Cooperativa en Enfermedades Cardiovasculares (RD12/0042/0045 to I. Flores). The CNIC is supported by the Ministerio de Economia y Competitividad and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (Ministerio de Economia y Competitividad award SEV-2015-0505).
dc.language.isoeng
dc.publisherRockefeller University Press 
dc.type.hasVersionVoR
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectMOUSE HEART
dc.subjectTERMINAL TRANSFERASE
dc.subjectCARDIAC REGENERATION
dc.subjectOXIDATIVE STRESS
dc.subjectMAMMALIAN HEART
dc.subjectSTEM-CELLS
dc.subjectPROLIFERATION
dc.subjectEXPRESSION
dc.subjectCANCER
dc.subjectMICE
dc.titlePostnatal telomere dysfunction induces cardiomyocyte cell-cycle arrest through p21 activation
dc.typejournal article
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.identifier.pubmedID27241915
dc.format.volume213
dc.format.page571-583
dc.identifier.doi10.1083/jcb.201510091
dc.contributor.funderMinisterio de Educación (España) 
dc.contributor.funderMinisterio de Economía y Competitividad (España) 
dc.contributor.funderAsociación Española Contra el Cáncer 
dc.contributor.funderCentro de Investigación Biomédica en Red - CIBERCV (Enfermedades Cardiovasculares) 
dc.contributor.funderFundación ProCNIC 
dc.contributor.funderMinisterio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España) 
dc.description.peerreviewed
dc.identifier.e-issn1540-8140
dc.relation.publisherversionhttps://doi.org/10.1083/jcb.201510091
dc.identifier.journalJournal of Cell Biology
dc.repisalud.orgCNICCNIC::Grupos de investigación::Regeneración y envejecimiento
dc.repisalud.institucionCNIC
dc.relation.projectIDMINECO/ICTI2013-2016/SEV-2015-0505es_ES
dc.rights.accessRightsopen accesses_ES


Ficheros en el ítem

Acceso Abierto
Thumbnail
Acceso Abierto
Thumbnail

Este ítem aparece en la(s) siguiente(s) colección(ones)

Mostrar el registro sencillo del ítem

Atribución-NoComercial-CompartirIgual 4.0 Internacional
Este Item está sujeto a una licencia Creative Commons: Atribución-NoComercial-CompartirIgual 4.0 Internacional