Transcriptional regulation of Sox2 by the retinoblastoma family of pocket proteins
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- dc.contributor.author Vilas, Jéssica M.ca
- dc.contributor.author Ferreirós, Albaca
- dc.contributor.author Carneiro, Carmenca
- dc.contributor.author Morey Ramonell, Lluísca
- dc.contributor.author Silva-Álvarez, Sabela daca
- dc.contributor.author Fernandes, Tâniaca
- dc.contributor.author Abad, Maríaca
- dc.contributor.author Di Croce, Lucianoca
- dc.contributor.author García Caballero, Tomásca
- dc.contributor.author Serrano, Manuelca
- dc.contributor.author Rivas, Carmenca
- dc.contributor.author Vidal, Anxoca
- dc.contributor.author Collado, Manuelca
- dc.date.accessioned 2015-11-18T13:29:27Z
- dc.date.available 2015-11-18T13:29:27Z
- dc.date.issued 2015
- 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.ca
- dc.format.mimetype application/pdfca
- dc.identifier.citation Vilas JM, Ferreirós A, Carneiro C, Morey L, Da Silva-Álvarez S, Fernandes T et al. Transcriptional regulation of Sox2 by the retinoblastoma family of pocket proteins. Oncotarget. 2015;6(5):2992-3002. DOI: 10.18632/oncotarget.2996ca
- dc.identifier.doi http://dx.doi.org/10.18632/oncotarget.2996
- dc.identifier.issn 1949-2553
- dc.identifier.uri http://hdl.handle.net/10230/25136
- dc.language.iso engca
- dc.publisher Impact Journalsca
- dc.relation.ispartof Oncotarget. 2015;6(5):2992-3002
- dc.rights This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ca
- dc.rights.accessRights info:eu-repo/semantics/openAccessca
- dc.rights.uri https://creativecommons.org/licenses/by/4.0/
- dc.subject.keyword Retinoblastoma
- dc.subject.keyword Sox2
- dc.subject.keyword Stem cells
- dc.subject.keyword Cancer
- dc.subject.other Cèl·lules mare
- dc.subject.other Càncer
- dc.title Transcriptional regulation of Sox2 by the retinoblastoma family of pocket proteinsca
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/publishedVersionca