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Ckap2 regulates aneuploidy, cell cycling, and cell death in a p53-dependent manner

Katsuya Tsuchihara1, Valentina Lapin, Christopher Bakal

  • 1The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, Ontario, Canada.

Cancer Research
|August 3, 2005
PubMed

Insights

Cytoskeleton associated protein 2 (CKAP2) is a novel p53 target gene. CKAP2 stabilizes microtubules and, in p53-null cells, induces tetraploidy, suggesting a role in cell cycle regulation.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • The p53 tumor suppressor is a critical regulator of cellular responses to DNA damage.
  • Identifying novel p53 target genes is crucial for understanding its multifaceted roles in cancer prevention.

Purpose of the Study:

  • To identify novel p53 target genes using DNA microarray screening.
  • To elucidate the function of Ckap2 (cytoskeleton associated protein 2) in cellular processes regulated by p53.

Main Methods:

  • DNA microarray screening in a mouse erythroleukemia cell line.
  • Analysis of CKAP2 expression in human and mouse cells following DNA damage.
  • Investigation of CKAP2's effect on microtubules, centrosome numbers, and cell cycle progression in p53-null and p53-competent cells.

Main Results:

  • Ckap2 was identified as a novel p53 target gene.
  • DNA damage induced CKAP2 expression in a p53-dependent manner.
  • Overexpressed Ckap2 stabilized microtubules and, in p53-null cells, led to tetraploidy and aberrant centrosome numbers, indicating disrupted mitosis.
  • In p53-competent cells, Ckap2 induced p53-mediated cell cycle arrest and apoptosis without causing tetraploidy.

Conclusions:

  • CKAP2 is a novel p53 target gene involved in microtubule stabilization.
  • CKAP2 plays a role in regulating cell cycle checkpoints and preventing aneuploidy.
  • A positive feedback loop exists where Ckap2 activates the G1 tetraploidy checkpoint, contributing to p53-mediated tumor suppression.

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