The tumor suppressor p53 connects ribosome biogenesis to cell cycle control: a double-edged sword

Michael Hölzel1,2, Kaspar Burger1, Bastian Mühl1

  • 1Department of Molecular Epigenetics, Center of Integrated Protein Science (CIPSM), Helmholtz Center Munich, Munich, Germany.

Oncotarget
|February 5, 2011
PubMed

Insights

The p53 protein, known as the guardian of the genome, responds to DNA damage and non-genotoxic stress. Its stabilization involves modifications that direct cellular responses like cell cycle arrest or cell death, especially when ribosome biogenesis is impacted.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • The p53 protein, described over 30 years ago, is a key regulator of cellular responses.
  • P53 is recognized as the 'guardian of the genome' due to its role in sensing genetic alterations.
  • Cellular stress, particularly DNA damage, triggers p53 stabilization through complex post-translational modifications.

Purpose of the Study:

  • To elucidate the multifaceted roles of the p53 protein in cellular regulation.
  • To understand the mechanisms by which p53 responds to various forms of cellular stress.
  • To investigate the involvement of p53 in non-genotoxic stress, specifically related to ribosome biogenesis.

Main Methods:

  • Literature review of p53 research over the past three decades.
  • Analysis of studies detailing p53 post-translational modifications upon DNA damage.
  • Examination of recent findings on p53's response to non-genotoxic stressors affecting ribosome biogenesis.

Main Results:

  • P53 exhibits versatile functions, acting as a critical sensor for genetic instability.
  • DNA damage induces p53 stabilization, leading to modifications that dictate cell cycle arrest or apoptosis.
  • Emerging evidence shows p53 also responds to non-genotoxic stress, notably when ribosome biogenesis is compromised.

Conclusions:

  • P53 plays a pivotal role in maintaining genomic integrity and orchestrating cellular fate.
  • The modification patterns of p53 are crucial for determining the outcome of cellular stress responses.
  • The newly identified role of p53 in ribosome biogenesis-related stress expands our understanding of its regulatory network.

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