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Analysis of Cell Cycle Position in Mammalian Cells
12:19

Analysis of Cell Cycle Position in Mammalian Cells

Published on: January 21, 2012

Functional interaction of STAT3 transcription factor with the cell cycle inhibitor p21WAF1/CIP1/SDI1

O Coqueret1, H Gascan

  • 1INSERM E-9928, 4 Rue Larrey, CHU Angers, 49033 Angers Cedex, France. oliver.coqueret@univ-angers.fr

The Journal of Biological Chemistry
|April 15, 2000
PubMed

Insights

The cyclin-dependent kinase inhibitor p21, also known as p21(WAF1/CIP1/SDI1), inhibits STAT3 transcriptional activation by interacting with STAT3 and the CREB-binding protein. This reveals a novel inhibitory role for p21 in STAT3 signaling pathways.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Biochemistry

Background:

  • Signal transducers and activators of transcription (STAT) factors regulate gene expression following cytokine stimulation.
  • STAT protein activation involves phosphorylation, dimerization, nuclear translocation, and target gene activation, followed by transient down-regulation.

Purpose of the Study:

  • To investigate the role of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1/SDI1) in STAT3 transcriptional activation.
  • To elucidate the mechanism by which p21(WAF1/CIP1/SDI1) might regulate STAT3 signaling.

Main Methods:

  • Coimmunoprecipitation and pull-down assays to detect protein-protein interactions.
  • In vivo overexpression studies to assess the effect of p21(WAF1/CIP1/SDI1) on STAT3 transcriptional activity.
  • Analysis of STAT3 DNA binding activity.

Main Results:

  • p21(WAF1/CIP1/SDI1) associates with STAT3 proteins.
  • Overexpression of p21(WAF1/CIP1/SDI1) inhibits STAT3 transcriptional activation without affecting STAT3 DNA binding.
  • p21(WAF1/CIP1/SDI1) interacts with CREB-binding protein, and its inhibitory effect on STAT3 is blocked by CREB-binding protein overexpression.

Conclusions:

  • p21(WAF1/CIP1/SDI1) acts as an inhibitor of STAT3 transcriptional activation.
  • The inhibitory mechanism involves interaction with STAT3 and modulation of the CREB-binding protein coactivator.
  • This study identifies a novel function for p21(WAF1/CIP1/SDI1) as a regulator of STAT signaling.

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