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Ribosomal stress induces L11- and p53-dependent apoptosis in mouse pluripotent stem cells

Lucia Morgado-Palacin1, Susana Llanos, Manuel Serrano

  • 1Spanish National Cancer Research Center, Madrid, Spain.

Cell Cycle (Georgetown, Tex.)
|January 21, 2012
PubMed

Insights

Ribosomal stress activates the tumor suppressor p53 in embryonic stem cells via the L11 protein. This pathway induces apoptosis, suggesting a role in early embryogenesis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Background:

  • Ribosome biogenesis is crucial for cellular homeostasis and is energetically demanding.
  • Disturbances in ribosome biogenesis trigger stress responses, including p53 activation, primarily studied in somatic and cancer cells.
  • The role of this pathway in embryonic pluripotent cells remained largely unknown.

Purpose of the Study:

  • To investigate the functionality of the ribosomal stress-p53 pathway in embryonic pluripotent cells.
  • To determine if ribosomal stress induces p53-dependent apoptosis in mouse embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs).

Main Methods:

  • Treatment of ESCs and iPSCs with low-dose Actinomycin D.
  • Depletion of ribosomal protein L37 using established methods.
  • Analysis of p53 activation and downstream target gene expression.
  • Assessment of apoptosis induction.

Main Results:

  • Low-dose Actinomycin D and L37 depletion induced p53 activation in ESCs and iPSCs in an L11-dependent manner.
  • p53 activation led to the transcriptional induction of p53 target genes, including p21, Mdm2, Pidd, Puma, Noxa, and Bax.
  • Ribosomal stress resulted in L11- and p53-dependent apoptosis in ESCs and iPSCs.

Conclusions:

  • The ribosomal stress-response pathway is functional in embryonic pluripotent cells.
  • This pathway, involving L11 and p53, mediates apoptosis in response to ribosomal stress in ESCs and iPSCs.
  • The findings suggest a potential role for ribosomal stress as a cellular checkpoint during early embryogenesis.

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