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Yeast As a Chassis for Developing Functional Assays to Study Human P53
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Published on: August 4, 2019

Critical role of the nucleolus in activation of the p53-dependent postmitotic checkpoint

Mai Tsuchiya1, Naohiro Katagiri, Takao Kuroda

  • 1Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8572, Japan.

Biochemical and Biophysical Research Communications
|March 15, 2011
PubMed

Insights

The nucleolus monitors prolonged mitosis, activating the G1 checkpoint via Myb-binding protein 1a (MYBBP1A) and p53. This ensures tetraploid cells arrest properly, preventing further cell cycle progression.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Cells can arrest in mitosis due to spindle checkpoint activation.
  • Prolonged mitotic arrest leads to tetraploid cells that enter G1 phase.
  • The postmitotic G1 checkpoint, regulated by p53, controls cell cycle progression in these cells.

Purpose of the Study:

  • To investigate the role of the nucleolus in activating the postmitotic G1 checkpoint.
  • To identify nucleolar factors involved in regulating p53 during prolonged mitosis.

Main Methods:

  • Cell culture and synchronization.
  • Immunofluorescence microscopy to track protein localization.
  • Western blotting to assess protein levels and modifications (acetylation).
  • Co-immunoprecipitation to study protein interactions.

Main Results:

  • The nucleolus is disrupted during mitosis, with proteins translocating to the cytoplasm.
  • Myb-binding protein 1a (MYBBP1A) accumulates in the cytoplasm during prolonged mitosis.
  • MYBBP1A enhances the interaction between p300 and p53, leading to p53 acetylation and accumulation.
  • p53 activation mediated by MYBBP1A is crucial for G1 arrest in tetraploid cells.

Conclusions:

  • The nucleolus plays a critical role in sensing prolonged mitosis.
  • MYBBP1A acts as a key nucleolar factor that links prolonged mitosis to p53 activation.
  • This pathway is essential for the postmitotic G1 checkpoint, ensuring cell cycle arrest in tetraploid cells.

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