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p53 displacement from centrosomes and p53-mediated G1 arrest following transient inhibition of the mitotic spindle

M Ciciarello1, R Mangiacasale, M Casenghi

  • 1Consiglio Nazionale delle Ricerche Centre of Evolutionary Genetics, Department of Genetics and Molecular Biology, University of Rome "La Sapienza," Via degli Apuli 4, Rome 00185, Italy.

The Journal of Biological Chemistry
|May 29, 2001
PubMed

Insights

Transient spindle damage activates p53, a tumor suppressor, leading to cell cycle arrest. This occurs even after spindle repair, suggesting p53 localization disruption is key to preventing cell division errors.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • The p53 protein is crucial for cell cycle arrest following mitotic spindle defects.
  • Preventing rereplication is vital in cells with failed mitotic division.

Purpose of the Study:

  • To investigate the effect of transient spindle assembly inhibition on p53 activation and cell cycle progression.
  • To determine if p53 can signal cell cycle inhibition after spindle damage is repaired.

Main Methods:

  • Transient exposure of cells to nocodazole, a tubulin-depolymerizing agent.
  • Monitoring p53 and p21 expression levels.
  • Assessing cell cycle arrest in G1 phase.
  • Investigating p53 association with centrosomes during mitosis.

Main Results:

  • Transient nocodazole treatment causes stable p53 activation.
  • High p53 and p21 levels persist, leading to G1 arrest in the subsequent cell cycle.
  • Nocodazole disrupts the normal association of p53 with centrosomes in mitotic cells.
  • Cell cycle arrest occurs irrespective of ploidy after mitotic exit.

Conclusions:

  • Transient spindle damage induces a lasting cell cycle inhibitory signal mediated by p53.
  • Disruption of p53's subcellular localization at centrosomes is a key mechanism.
  • This interference dictates cell cycle arrest in cells originating from defective mitoses.

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