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p53 induces differentiation of mouse embryonic stem cells by suppressing Nanog expression

Tongxiang Lin1, Connie Chao, Shin'ichi Saito

  • 1Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0322, USA.

Nature Cell Biology
|December 28, 2004
PubMed

Insights

The tumor suppressor p53 plays a new role in embryonic stem cell (ESC) differentiation by suppressing Nanog expression. This process, crucial for maintaining genetic stability, involves p53 phosphorylation and co-repressor recruitment.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • The tumor suppressor p53 is activated by stress signals like DNA damage, inducing cell-cycle arrest or apoptosis.
  • Embryonic stem cells (ESCs) possess self-renewal capacity maintained by genes like Nanog.

Purpose of the Study:

  • To investigate a novel role for p53 in mouse ESC differentiation.
  • To elucidate the mechanism by which p53 influences Nanog expression during differentiation.

Main Methods:

  • Analysis of p53 binding to the Nanog promoter.
  • Assessment of Nanog mRNA levels during ESC differentiation.
  • Study of p53 Ser 315 phosphorylation and its impact on p53 activity.
  • Investigation of mSin3a co-repressor recruitment to the Nanog promoter in wild-type and p53(S315A) knock-in ESCs.

Main Results:

  • p53 suppresses Nanog expression in ESCs following DNA damage.
  • Nanog down-regulation during differentiation correlates with p53 transcriptional activity and Ser 315 phosphorylation.
  • Impaired p53 activity and inefficient Nanog suppression were observed in p53(S315A) knock-in ESCs.
  • p53(S315A) ESCs showed impaired recruitment of the mSin3a co-repressor to the Nanog promoter.

Conclusions:

  • p53 promotes ESC differentiation by suppressing Nanog expression, a novel function.
  • Ser 315 phosphorylation of p53 is critical for its transcriptional activity and mSin3a recruitment during differentiation.
  • This mechanism contributes to maintaining genetic stability in ESCs by promoting differentiation.

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