p53 induces differentiation of mouse embryonic stem cells by suppressing Nanog expression
Top Cited Papers
- 26 December 2004
- journal article
- research article
- Published by Springer Nature in Nature Cell Biology
- Vol. 7 (2), 165-171
- https://doi.org/10.1038/ncb1211
Abstract
The tumour suppressor p53 becomes activated in response to upstream stress signals, such as DNA damage, and causes cell-cycle arrest or apoptosis1. Here we report a novel role for p53 in the differentiation of mouse embryonic stem cells (ESCs). p53 binds to the promoter of Nanog, a gene required for ESC self-renewal2,3, and suppresses Nanog expression after DNA damage. The rapid down-regulation of Nanog mRNA during ESC differentiation correlates with the induction of p53 transcriptional activity and Ser 315 phosphorylation. The importance of Ser 315 phosphorylation was revealed by the finding that induction of p53 activity is impaired in p53S315A knock-in ESCs during differentiation, leading to inefficient suppression of Nanog expression. The decreased inhibition of Nanog expression in p53S315A ESCs during differentiation is due to an impaired recruitment of the co-repressor mSin3a to the Nanog promoter. These findings indicate an alternative mechanism for p53 to maintain genetic stability in ESCs, by inducing the differentiation of ESCs into other cell types that undergo efficient p53-dependent cell-cycle arrest and apoptosis.Keywords
This publication has 22 references indexed in Scilit:
- The Homeoprotein Nanog Is Required for Maintenance of Pluripotency in Mouse Epiblast and ES CellsCell, 2003
- Functional Expression Cloning of Nanog, a Pluripotency Sustaining Factor in Embryonic Stem CellsCell, 2003
- Regulation of p53 responses by post-translational modificationsCell Death & Differentiation, 2003
- Transcriptional Repression of the Anti-apoptoticsurvivin Gene by Wild Type p53Journal of Biological Chemistry, 2002
- Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cellsNature Genetics, 2000
- Induction of Cellular Differentiation by Retinoic Acid in vitroCells Tissues Organs, 1999
- Regulation of ES cell differentiation by functional and conformational modulation of p53The EMBO Journal, 1997
- A functionally inactive p53 protein interatocarcinoma cells is activated by either DNA damage or cellular differentiationNature Medicine, 1996
- p53: puzzle and paradigm.Genes & Development, 1996
- A novel octamer binding transcription factor is differentially expressed in mouse embryonic cellsCell, 1990