Cargando…
Transcriptional regulation of Sox2 by the retinoblastoma family of pocket proteins
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...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413632/ https://www.ncbi.nlm.nih.gov/pubmed/25576924 |
_version_ | 1782368811098308608 |
---|---|
author | Vilas, Jéssica M. Ferreirós, Alba Carneiro, Carmen Morey, Lluis Silva-Álvarez, Sabela Da Fernandes, Tânia Abad, María Croce, Luciano Di García-Caballero, Tomás Serrano, Manuel Rivas, Carmen Vidal, Anxo Collado, Manuel |
author_facet | Vilas, Jéssica M. Ferreirós, Alba Carneiro, Carmen Morey, Lluis Silva-Álvarez, Sabela Da Fernandes, Tânia Abad, María Croce, Luciano Di García-Caballero, Tomás Serrano, Manuel Rivas, Carmen Vidal, Anxo Collado, Manuel |
author_sort | Vilas, Jéssica M. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4413632 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-44136322015-05-08 Transcriptional regulation of Sox2 by the retinoblastoma family of pocket proteins Vilas, Jéssica M. Ferreirós, Alba Carneiro, Carmen Morey, Lluis Silva-Álvarez, Sabela Da Fernandes, Tânia Abad, María Croce, Luciano Di García-Caballero, Tomás Serrano, Manuel Rivas, Carmen Vidal, Anxo Collado, Manuel Oncotarget Research Paper 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. Impact Journals LLC 2014-12-18 /pmc/articles/PMC4413632/ /pubmed/25576924 Text en Copyright: © 2015 Vilas et al. http://creativecommons.org/licenses/by/2.5/ 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. |
spellingShingle | Research Paper Vilas, Jéssica M. Ferreirós, Alba Carneiro, Carmen Morey, Lluis Silva-Álvarez, Sabela Da Fernandes, Tânia Abad, María Croce, Luciano Di García-Caballero, Tomás Serrano, Manuel Rivas, Carmen Vidal, Anxo Collado, Manuel Transcriptional regulation of Sox2 by the retinoblastoma family of pocket proteins |
title | Transcriptional regulation of Sox2 by the retinoblastoma family of pocket proteins |
title_full | Transcriptional regulation of Sox2 by the retinoblastoma family of pocket proteins |
title_fullStr | Transcriptional regulation of Sox2 by the retinoblastoma family of pocket proteins |
title_full_unstemmed | Transcriptional regulation of Sox2 by the retinoblastoma family of pocket proteins |
title_short | Transcriptional regulation of Sox2 by the retinoblastoma family of pocket proteins |
title_sort | transcriptional regulation of sox2 by the retinoblastoma family of pocket proteins |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413632/ https://www.ncbi.nlm.nih.gov/pubmed/25576924 |
work_keys_str_mv | AT vilasjessicam transcriptionalregulationofsox2bytheretinoblastomafamilyofpocketproteins AT ferreirosalba transcriptionalregulationofsox2bytheretinoblastomafamilyofpocketproteins AT carneirocarmen transcriptionalregulationofsox2bytheretinoblastomafamilyofpocketproteins AT moreylluis transcriptionalregulationofsox2bytheretinoblastomafamilyofpocketproteins AT silvaalvarezsabelada transcriptionalregulationofsox2bytheretinoblastomafamilyofpocketproteins AT fernandestania transcriptionalregulationofsox2bytheretinoblastomafamilyofpocketproteins AT abadmaria transcriptionalregulationofsox2bytheretinoblastomafamilyofpocketproteins AT crocelucianodi transcriptionalregulationofsox2bytheretinoblastomafamilyofpocketproteins AT garciacaballerotomas transcriptionalregulationofsox2bytheretinoblastomafamilyofpocketproteins AT serranomanuel transcriptionalregulationofsox2bytheretinoblastomafamilyofpocketproteins AT rivascarmen transcriptionalregulationofsox2bytheretinoblastomafamilyofpocketproteins AT vidalanxo transcriptionalregulationofsox2bytheretinoblastomafamilyofpocketproteins AT colladomanuel transcriptionalregulationofsox2bytheretinoblastomafamilyofpocketproteins |