Transcriptional regulation of Sox2 by the retinoblastoma family of pocket proteins

Jéssica M. Vilas, Alba Ferreirós, Carmen Carneiro, Lluis Morey, Sabela Da Silva-álvarez, Tânia Fernandes, María Abad, Luciano Di Croce, Tomás García-Caballero, Manuel Serrano, Carmen Rivas, Anxo Vidal, Manuel Collado

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2992-3002
Number of pages11
JournalOncotarget
Volume6
Issue number5
DOIs
StatePublished - 2015
Externally publishedYes

Keywords

  • Cancer
  • Retinoblastoma
  • Sox2
  • Stem cells

ASJC Scopus subject areas

  • Oncology

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