p53 is required for etoposide-induced apoptosis of human embryonic stem cells

Grandela, C., Pera, M. F. and Wolvetang, E. J. (2008) p53 is required for etoposide-induced apoptosis of human embryonic stem cells. Stem Cell Research, 1 2: 116-128. doi:10.1016/j.scr.2007.10.003

Author Grandela, C.
Pera, M. F.
Wolvetang, E. J.
Title p53 is required for etoposide-induced apoptosis of human embryonic stem cells
Journal name Stem Cell Research   Check publisher's open access policy
ISSN 1873-5061
Publication date 2008-06-01
Year available 2007
Sub-type Article (original research)
DOI 10.1016/j.scr.2007.10.003
Open Access Status DOI
Volume 1
Issue 2
Start page 116
End page 128
Total pages 13
Place of publication Amsterdam, Netherlands
Publisher Elsevier BV
Language eng
Abstract The molecular mechanisms controlling DNA-damage-induced apoptosis of human embryonic stem cells (hESC) are poorly understood. Here we investigate the role of p53 in etoposide-induced apoptosis. We show that p53 is constitutively expressed at high levels in the cytoplasm of hESC. Etoposide treatment results in a rapid and extensive induction of apoptosis and leads to a further increase in p53 and PUMA expression as well as Bax processing. p53 both translocates to the nucleus and associates with the mitochondria, accompanied by colocalization of Bax with Mcl1. hESC stably transduced with p53 shRNA display 80% reduction of endogenous p53 and exhibit an 80% reduction in etoposide-induced apoptosis accompanied by constitutive downregulation of Bax and an attenuated upregulation of PUMA. Our data further show that undifferentiated hESC that express Oct4 are much more sensitive to etoposide-induced apoptosis than their more differentiated progeny. Our study demonstrates that p53 is required for etoposide-induced apoptosis of hESC and reveals, at least in part, the molecular mechanism of DNA-damage-induced apoptosis in hESC.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes Available online 22 October 2007

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Australian Institute for Bioengineering and Nanotechnology Publications
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Citation counts: TR Web of Science Citation Count  Cited 13 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 12 Feb 2009, 22:46:41 EST by Judy Dingwall on behalf of Aust Institute for Bioengineering & Nanotechnology