The p53 inhibitor, pifithrin-α, suppresses self-renewal of embryonic stem cells

Essam Mohamed, Ikuo Tooyama

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 languageEnglish
Pages (from-to)605-610
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume420
Issue number3
DOIs
Publication statusPublished - 13 Apr 2012
Externally publishedYes

Fingerprint

Embryonic Stem Cells
Stem cells
Induced Pluripotent Stem Cells
Cyclin D1
Cell Cycle Checkpoints
pifithrin
DNA
Cell proliferation
Transcriptional Activation
DNA Damage
Cell Count
Cell Proliferation
Genes
Chemical activation
Cells

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 journalArticle

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