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p21 Disrupts the interaction between cdk2 and the E2F-p130 complex

P Shiyanov1, S Bagchi, G Adami

  • 1Department of Biochemistry, University of Illinois at Chicago, Illinois 60612, USA.

Molecular and Cellular Biology
|March 1, 1996
PubMed

Insights

The p21 protein disrupts the E2F-p130 complex, releasing cdk2 and inhibiting cell cycle progression. This finding suggests p21 mediates p53

Area of Science:

  • Molecular Biology
  • Cell Cycle Regulation
  • Cancer Research

Background:

  • Transcription factor E2F binds retinoblastoma-related protein p130 in growth-arrested cells, inhibiting cell cycle progression.
  • Cyclin-dependent kinase 2 (cdk2) binds to the E2F-p130 complex during G1 phase progression.

Purpose of the Study:

  • To investigate the role of p21 in the disruption of the E2F-p130-cdk2 complex.
  • To elucidate the mechanism by which p53-mediated growth suppression occurs.

Main Methods:

  • Fractionation of mouse L-cell extracts to isolate the E2F-p130-cdk2 complex.
  • Incubation of the complex with recombinant p21 in cell lines expressing a temperature-sensitive p53 mutant.
  • Analysis of reporter gene expression containing E2F binding sites.

Main Results:

  • Recombinant p21 disrupted the interaction between cdk2 and the E2F-p130 complex.
  • Increased p21 levels correlated with reduced cdk2 association with the E2F-p130 complex.
  • p21 coexpression reduced the activity of a reporter gene driven by E2F-responsive elements.

Conclusions:

  • The p21 protein mediates the disruption of the E2F-p130-cdk2 complex.
  • This disruption is a key mechanism in the growth-suppressive function of p53.

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