2024-03-29T05:13:27Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/103602022-10-13T07:33:46Zcom_20.500.12105_2174com_20.500.12105_2051com_20.500.12105_2173col_20.500.12105_2175
00925njm 22002777a 4500
dc
Vilas, Jéssica M
author
Ferreirós, Alba
author
Carneiro, Carmen
author
Morey, Lluis
author
Da Silva-Álvarez, Sabela
author
Fernandes, Tânia
author
Di Croce, Luciano
author
García-Caballero, Tomás
author
Rivas, Carmen
author
Vidal, Anxo
author
Serrano Marugan, Manuel
author
2015-02-20
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.
Oncotarget .2015;6(5):2992-3002.
http://hdl.handle.net/20.500.12105/10360
25576924
10.18632/oncotarget.2996
1949-2553
Oncotarget
IPS CELLS
RB FAMILY
STEM
SUPPRESSION
PATHWAY
MOUSE
GENE
MECHANISMS
MICE
Transcriptional regulation of Sox2 by the retinoblastoma family of pocket proteins.