Abstract
Recent studies have reported the role of p53 in suppressing the pluripotency of embryonic stem (ES) cells after DNA damage and blocking the reprogramming of somatic cells into induced pluripotent stem (iPS) cells. However, to date no evidence has been presented to support the function of p53 in unstressed ES cells. In this study, we investigated the effect of pifithrin (PFT)-α, an inhibitor of p53-dependent transcriptional activation, on self-renewal of ES cells. Our results revealed that treatment of ES cells with PFT-α resulted in the inhibition of ES cell propagation in a dose-dependent manner, as indicated by a marked reduction in the cell number and colony size. Also, PFT-α caused a cell cycle arrest and significant reduction in DNA synthesis. In addition, inhibition of p53 activity reduced the expression levels of cyclin D1 and Nanog. These findings indicate that p53 pathway in ES cells rather than acting as an inactive gene, is required for ES cell proliferation and self-renewal under unstressful conditions.
Original language | English |
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Pages (from-to) | 605-610 |
Number of pages | 6 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 420 |
Issue number | 3 |
DOIs | |
Publication status | Published - 13 Apr 2012 |
Externally published | Yes |
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Keywords
- Cyclin D1
- ES cells
- Nanog
- Proliferation
- Tumor suppressor gene
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
The p53 inhibitor, pifithrin-α, suppresses self-renewal of embryonic stem cells. / Mohamed, Essam; Tooyama, Ikuo.
In: Biochemical and Biophysical Research Communications, Vol. 420, No. 3, 13.04.2012, p. 605-610.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The p53 inhibitor, pifithrin-α, suppresses self-renewal of embryonic stem cells
AU - Mohamed, Essam
AU - Tooyama, Ikuo
PY - 2012/4/13
Y1 - 2012/4/13
N2 - Recent studies have reported the role of p53 in suppressing the pluripotency of embryonic stem (ES) cells after DNA damage and blocking the reprogramming of somatic cells into induced pluripotent stem (iPS) cells. However, to date no evidence has been presented to support the function of p53 in unstressed ES cells. In this study, we investigated the effect of pifithrin (PFT)-α, an inhibitor of p53-dependent transcriptional activation, on self-renewal of ES cells. Our results revealed that treatment of ES cells with PFT-α resulted in the inhibition of ES cell propagation in a dose-dependent manner, as indicated by a marked reduction in the cell number and colony size. Also, PFT-α caused a cell cycle arrest and significant reduction in DNA synthesis. In addition, inhibition of p53 activity reduced the expression levels of cyclin D1 and Nanog. These findings indicate that p53 pathway in ES cells rather than acting as an inactive gene, is required for ES cell proliferation and self-renewal under unstressful conditions.
AB - Recent studies have reported the role of p53 in suppressing the pluripotency of embryonic stem (ES) cells after DNA damage and blocking the reprogramming of somatic cells into induced pluripotent stem (iPS) cells. However, to date no evidence has been presented to support the function of p53 in unstressed ES cells. In this study, we investigated the effect of pifithrin (PFT)-α, an inhibitor of p53-dependent transcriptional activation, on self-renewal of ES cells. Our results revealed that treatment of ES cells with PFT-α resulted in the inhibition of ES cell propagation in a dose-dependent manner, as indicated by a marked reduction in the cell number and colony size. Also, PFT-α caused a cell cycle arrest and significant reduction in DNA synthesis. In addition, inhibition of p53 activity reduced the expression levels of cyclin D1 and Nanog. These findings indicate that p53 pathway in ES cells rather than acting as an inactive gene, is required for ES cell proliferation and self-renewal under unstressful conditions.
KW - Cyclin D1
KW - ES cells
KW - Nanog
KW - Proliferation
KW - Tumor suppressor gene
UR - http://www.scopus.com/inward/record.url?scp=84859599194&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84859599194&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2012.03.041
DO - 10.1016/j.bbrc.2012.03.041
M3 - Article
C2 - 22445757
AN - SCOPUS:84859599194
VL - 420
SP - 605
EP - 610
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -