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Updated: Aug 14, 2026

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

CDK5 is a novel regulatory protein in PPARgamma ligand-induced antiproliferation

Eugene Kim1, Fei Chen, Chia-Chi Wang

  • 1Division of Surgical Oncology, UMDNJ-New Jersey Medical School, Newark, NJ 07103, USA.

International Journal of Oncology
|December 6, 2005
PubMed

Insights

Cyclin-dependent kinase 5 (Cdk5) is elevated in colon cancer. Its activity is reduced by ciglitazone, inhibiting cancer cell proliferation, and overexpression reverses this effect.

Area of Science:

  • Cell Biology
  • Molecular Oncology

Background:

  • Cyclin-dependent kinase 5 (Cdk5) is primarily known for its role in neuronal differentiation.
  • The role of Cdk5 in cancer, particularly colon cancer, remains largely unexplored.

Purpose of the Study:

  • To investigate the expression and activity of Cdk5 in colon cancer cells.
  • To determine the involvement of Cdk5 in PPARgamma ligand-induced antiproliferation of colon cancer cells.

Main Methods:

  • Western blot analysis to assess Cdk5 and p35 protein levels.
  • Kinase assays to measure Cdk5 activity.
  • Treatment of HT-29 colon cancer cells with ciglitazone (a PPARgamma ligand).
  • Cdk5 overexpression studies.

Main Results:

  • Cdk5 protein levels and kinase activity were significantly higher in HT-29 colon cancer cells and human tumor tissue compared to normal colonic mucosa.
  • Ciglitazone treatment led to a dose- and time-dependent decrease in HT-29 cell proliferation, accompanied by reduced Cdk5 expression and activity.
  • Overexpression of Cdk5 reversed the antiproliferative effects of ciglitazone.
  • The regulatory protein p35 showed no significant changes in expression upon ciglitazone treatment.

Conclusions:

  • Cdk5 is expressed and active in colon cancer cells.
  • Cdk5 plays a role in the antiproliferative effects of PPARgamma ligands like ciglitazone in colon cancer.
  • Targeting Cdk5 may represent a therapeutic strategy for colon cancer.

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