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P53 is active in murine stem cells and alters the transcriptome in a manner that is reminiscent of mutant p53

Yan, H. 1; Solozobova, V. 1; Zhang, P. 1; Armant, O. 1; Kuehl, B. 2; Brenner-Weiss, G. 2; Blattner, C. ORCID iD icon 1
1 Institut für Toxikologie und Genetik (ITG), Karlsruher Institut für Technologie (KIT)
2 Institut für Funktionelle Grenzflächen (IFG), Karlsruher Institut für Technologie (KIT)


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.

Verlagsausgabe §
DOI: 10.5445/IR/110103672
Veröffentlicht am 21.03.2018
DOI: 10.1038/cddis.2015.33
Zitationen: 13
Zitationen: 14
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Toxikologie und Genetik (ITG)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2015
Sprache Englisch
Identifikator ISSN: 2041-4889
KITopen-ID: 110103672
HGF-Programm 47.01.01 (POF III, LK 01) Biol.Netzwerke u.Synth.Regulat. ITG+ITC
Erschienen in Cell Death and Disease
Verlag Springer Nature [academic journals on]
Band 6
Heft 2
Seiten e1662/1-11
Nachgewiesen in Web of Science
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