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dc.contributor.author | Vilas, Jéssica M | |
dc.contributor.author | Ferreirós, Alba | |
dc.contributor.author | Carneiro, Carmen | |
dc.contributor.author | Morey, Lluis | |
dc.contributor.author | Da Silva-Álvarez, Sabela | |
dc.contributor.author | Fernandes, Tânia | |
dc.contributor.author | Di Croce, Luciano | |
dc.contributor.author | García-Caballero, Tomás | |
dc.contributor.author | Rivas, Carmen | |
dc.contributor.author | Vidal, Anxo | |
dc.contributor.author | Serrano Marugan, Manuel | |
dc.date.accessioned | 2020-06-11T16:23:01Z | |
dc.date.available | 2020-06-11T16:23:01Z | |
dc.date.issued | 2015-02-20 | |
dc.identifier.citation | Oncotarget .2015;6(5):2992-3002. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/10360 | |
dc.description.abstract | Cellular reprogramming to iPSCs has uncovered unsuspected links between tumor suppressors and pluripotency factors. Using this system, it was possible to identify tumor suppressor p27 as a repressor of Sox2 during differentiation. This led to the demonstration that defects in the repression of Sox2 can contribute to tumor development. The members of the retinoblastoma family of pocket proteins, pRb, p107 and p130, are negative regulators of the cell cycle with tumor suppressor activity and with roles in differentiation. In this work we studied the relative contribution of the retinoblastoma family members to the regulation of Sox2 expression. We found that deletion of Rb or p130 leads to impaired repression of Sox2, a deffect amplified by inactivation of p53. We also identified binding of pRb and p130 to an enhancer with crucial regulatory activity on Sox2 expression. Using cellular reprogramming we tested the impact of the defective repression of Sox2 and confirmed that Rb deficiency allows the generation of iPSCs in the absence of exogenous Sox2. Finally, partial depletion of Sox2 positive cells reduced the pituitary tumor development initiated by Rb loss in vivo. In summary, our results show that Sox2 repression by pRb is a relevant mechanism of tumor suppression. | es_ES |
dc.description.sponsorship | We acknowledge the technical assistance of Pilar Alvarino. We are indebted to Patricia Viano for expert assistance with histological analysis. We thank Patricia Gonzalez, Maria Gomez and Virginia Alvarez for expert technical help with immunohistochemistry, and Han Li for critical reading of the manuscript. We are indebted to Konrad Hochedlinger for Sox2-TK ES cells. J.M.V. is a Xunta de Galicia predoctoral fellow. A.F. is an FPU predoctoral fellow from MECD. M.C. is a "Miguel Servet" investigator (ISCIII). Work in the laboratory of M.C. is funded by ISCIII (CP/11/00273). Work at the laboratory of A.V. is supported by grants from Xunta de Galicia (EM 2012/061) and MICINN (SAF2009-07389). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Impact Journals | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | * |
dc.subject | IPS CELLS | es_ES |
dc.subject | RB FAMILY | es_ES |
dc.subject | STEM | es_ES |
dc.subject | SUPPRESSION | es_ES |
dc.subject | PATHWAY | es_ES |
dc.subject | MOUSE | es_ES |
dc.subject | GENE | es_ES |
dc.subject | MECHANISMS | es_ES |
dc.subject | MICE | es_ES |
dc.subject.mesh | Transcription, Genetic | es_ES |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Cellular Reprogramming | es_ES |
dc.subject.mesh | Epigenesis, Genetic | es_ES |
dc.subject.mesh | Gene Expression Regulation, Developmental | es_ES |
dc.subject.mesh | Gene Expression Regulation, Neoplastic | es_ES |
dc.subject.mesh | Genotype | es_ES |
dc.subject.mesh | HEK293 Cells | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Induced Pluripotent Stem Cells | es_ES |
dc.subject.mesh | Mice, 129 Strain | es_ES |
dc.subject.mesh | Mice, Inbred C57BL | es_ES |
dc.subject.mesh | Mice, Knockout | es_ES |
dc.subject.mesh | Neoplastic Stem Cells | es_ES |
dc.subject.mesh | Phenotype | es_ES |
dc.subject.mesh | Pituitary Neoplasms | es_ES |
dc.subject.mesh | RNA Interference | es_ES |
dc.subject.mesh | Retinoblastoma Protein | es_ES |
dc.subject.mesh | Retinoblastoma-Like Protein p107 | es_ES |
dc.subject.mesh | Retinoblastoma-Like Protein p130 | es_ES |
dc.subject.mesh | SOXB1 Transcription Factors | es_ES |
dc.subject.mesh | Transfection | es_ES |
dc.subject.mesh | Tumor Suppressor Protein p53 | es_ES |
dc.title | Transcriptional regulation of Sox2 by the retinoblastoma family of pocket proteins. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución-NoComercial-CompartirIgual 4.0 Internacional | * |
dc.identifier.pubmedID | 25576924 | es_ES |
dc.format.volume | 6 | es_ES |
dc.format.number | 5 | es_ES |
dc.format.page | 2992-3002 | es_ES |
dc.identifier.doi | 10.18632/oncotarget.2996 | es_ES |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.contributor.funder | Xunta de Galicia (España) | |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1949-2553 | es_ES |
dc.relation.publisherversion | https://doi.org/10.18632/oncotarget.2996 | es_ES |
dc.identifier.journal | Oncotarget | es_ES |
dc.repisalud.institucion | CNIO | es_ES |
dc.repisalud.orgCNIO | CNIO::Grupos de investigación::Antiguos CNIO | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/SAF2009-07389 | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/CP/11/00273 | es_ES |
dc.rights.accessRights | open access | es_ES |