Publication: Transcriptional regulation of Sox2 by the retinoblastoma family of pocket proteins.
Loading...
Identifiers
Publication date
2015-02-20
Advisors
Journal Title
Journal ISSN
Volume Title
Publisher
Impact Journals
Metrics
Export
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.
Description
Keywords
MeSH Terms
Transcription, Genetic Animals Cellular Reprogramming Epigenesis, Genetic Gene Expression Regulation, Developmental Gene Expression Regulation, Neoplastic Genotype HEK293 Cells Humans Induced Pluripotent Stem Cells Mice, 129 Strain Mice, Inbred C57BL Mice, Knockout Neoplastic Stem Cells Phenotype Pituitary Neoplasms RNA Interference Retinoblastoma Protein Retinoblastoma-Like Protein p107 Retinoblastoma-Like Protein p130 SOXB1 Transcription Factors Transfection Tumor Suppressor Protein p53
DeCS Terms
Bibliographic citation
Oncotarget .2015;6(5):2992-3002.