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p53 is active in murine stem cells and alters the transcriptome in a manner that is reminiscent of mutant p53
Since it was found that p53 is highly expressed in murine embryonic stem cells, it remained a mystery whether p53 is active in this cell type. We show that a significant part of p53 is localised in the nucleus of murine embryonic stem cells and that the majority of this nuclear p53 is bound to DNA....
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669809/ https://www.ncbi.nlm.nih.gov/pubmed/25719246 http://dx.doi.org/10.1038/cddis.2015.33 |
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author | Yan, H Solozobova, V Zhang, P Armant, O Kuehl, B Brenner-Weiss, G Blattner, C |
author_facet | Yan, H Solozobova, V Zhang, P Armant, O Kuehl, B Brenner-Weiss, G Blattner, C |
author_sort | Yan, H |
collection | PubMed |
description | Since it was found that p53 is highly expressed in murine embryonic stem cells, it remained a mystery whether p53 is active in this cell type. We show that a significant part of p53 is localised in the nucleus of murine embryonic stem cells and that the majority of this nuclear p53 is bound to DNA. According to its nuclear localisation, we show that p53 alters the transcriptional program of stem cells. Nevertheless, the anti-proliferative activity of p53 is compromised in stem cells, and this control is due, at least in part, to the high amount of MdmX that is present in embryonic stem cells and bound to p53. Instead of the anti-proliferative activity that p53 has in differentiated cells, p53 controls transcription of pro-proliferative genes in embryonic stem cells including c-myc and c-jun. The impeded anti-proliferative activity of p53 and the induction of certain proto-oncogenes by p53 in murine embryonic stem cells can explain why stem cells proliferate efficiently despite having high levels of p53. |
format | Online Article Text |
id | pubmed-4669809 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-46698092015-12-08 p53 is active in murine stem cells and alters the transcriptome in a manner that is reminiscent of mutant p53 Yan, H Solozobova, V Zhang, P Armant, O Kuehl, B Brenner-Weiss, G Blattner, C Cell Death Dis Original Article Since it was found that p53 is highly expressed in murine embryonic stem cells, it remained a mystery whether p53 is active in this cell type. We show that a significant part of p53 is localised in the nucleus of murine embryonic stem cells and that the majority of this nuclear p53 is bound to DNA. According to its nuclear localisation, we show that p53 alters the transcriptional program of stem cells. Nevertheless, the anti-proliferative activity of p53 is compromised in stem cells, and this control is due, at least in part, to the high amount of MdmX that is present in embryonic stem cells and bound to p53. Instead of the anti-proliferative activity that p53 has in differentiated cells, p53 controls transcription of pro-proliferative genes in embryonic stem cells including c-myc and c-jun. The impeded anti-proliferative activity of p53 and the induction of certain proto-oncogenes by p53 in murine embryonic stem cells can explain why stem cells proliferate efficiently despite having high levels of p53. Nature Publishing Group 2015-02 2015-02-26 /pmc/articles/PMC4669809/ /pubmed/25719246 http://dx.doi.org/10.1038/cddis.2015.33 Text en Copyright © 2015 Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International Licence. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons licence, users will need to obtain permission from the licence holder to reproduce the material. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0 |
spellingShingle | Original Article Yan, H Solozobova, V Zhang, P Armant, O Kuehl, B Brenner-Weiss, G Blattner, C p53 is active in murine stem cells and alters the transcriptome in a manner that is reminiscent of mutant p53 |
title | p53 is active in murine stem cells and alters the transcriptome in a manner that is reminiscent of mutant p53 |
title_full | p53 is active in murine stem cells and alters the transcriptome in a manner that is reminiscent of mutant p53 |
title_fullStr | p53 is active in murine stem cells and alters the transcriptome in a manner that is reminiscent of mutant p53 |
title_full_unstemmed | p53 is active in murine stem cells and alters the transcriptome in a manner that is reminiscent of mutant p53 |
title_short | p53 is active in murine stem cells and alters the transcriptome in a manner that is reminiscent of mutant p53 |
title_sort | p53 is active in murine stem cells and alters the transcriptome in a manner that is reminiscent of mutant p53 |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669809/ https://www.ncbi.nlm.nih.gov/pubmed/25719246 http://dx.doi.org/10.1038/cddis.2015.33 |
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