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Less understood issues: p21(Cip1) in mitosis and its therapeutic potential

N-N Kreis1, F Louwen1, J Yuan1

  • 1Department of Gynecology and Obstetrics, J.W. Goethe-University, Frankfurt, Germany.

Oncogene
|May 27, 2014
PubMed

Insights

The cell cycle regulator p21 (also known as Cip1) is crucial for mitosis. Loss of p21 causes mitotic defects and genomic instability, while its stabilization in tumor cells suggests a role in cancer therapy.

Area of Science:

  • Cell Biology
  • Molecular Oncology

Background:

  • p21 (Cip1) is a key regulator of cellular processes, with dual roles as a tumor suppressor and oncogene.
  • Its role in mitosis, though proposed, has not been systematically investigated.
  • p21 expression is modulated by p53-dependent and -independent pathways in response to cellular stress.

Purpose of the Study:

  • To systematically investigate the function of p21 in mitosis.
  • To elucidate the role of p21 in mitotic progression and genomic stability.
  • To explore the therapeutic potential of p21 in cancer treatment.

Main Methods:

  • Biochemical assays to determine p21 binding and inhibition of Cdk1/cyclin B1 activity.
  • Analysis of mitotic progression, chromosome segregation, and cytokinesis in cells with and without p21.
  • Investigation of p21 stabilization and localization in mitotic tumor cells treated with mitotic agents.

Main Results:

  • p21 binds to and inhibits Cdk1/cyclin B1, ensuring precise mitotic progression.
  • Loss of p21 leads to prolonged mitosis, chromosome segregation errors, and cytokinesis failure, promoting genomic instability.
  • p21 is stabilized in the cytoplasm of mitotic tumor cells treated with paclitaxel or mitotic kinase inhibitors, correlating with cell survival.

Conclusions:

  • p21 plays a critical role in regulating mitosis and maintaining genomic stability.
  • Stabilized p21 in tumor cells suggests its involvement in resistance to mitotic agents and potential as a therapeutic target.

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