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AP2 inhibits cancer cell growth and activates p21WAF1/CIP1 expression

Y X Zeng1, K Somasundaram, W S el-Deiry

  • 1Howard Hughes Medical Institute, Department of Medicine and Genetics, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.

Nature Genetics
|January 1, 1997
PubMed

Insights

Activator protein AP2 regulates the cell cycle inhibitor p21WAF1/CIP1, promoting cell differentiation. This discovery links AP2 to controlling cell growth and division, offering new insights into developmental processes.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Developmental Biology

Background:

  • Activator Protein AP2 is a DNA-binding transcription factor involved in terminal differentiation.
  • AP2-null mice exhibit significant developmental abnormalities, but the underlying molecular mechanisms remain unclear.
  • p21WAF1/CIP1, a cell cycle inhibitor, is upregulated in terminally differentiating cells.

Purpose of the Study:

  • To investigate the role of AP2 in regulating p21WAF1/CIP1 expression during differentiation.
  • To elucidate the molecular mechanisms by which AP2 influences cell cycle control and growth.

Main Methods:

  • Utilized a p21 promoter-luciferase reporter assay with AP2 DNA-binding site mutagenesis.
  • Transfected cells with AP2 or control vectors.
  • Measured endogenous p21 protein levels and DNA synthesis.
  • Assessed cell division and colony formation in AP2-overexpressing cancer cell lines (HepG2, SW480).

Main Results:

  • Mutagenesis of the AP2 binding site in the p21 promoter abolished activation by AP2 or TPA.
  • AP2 transfection led to elevated endogenous p21 protein levels and inhibited DNA synthesis.
  • Overexpression of AP2 suppressed cell division and stable colony formation in HepG2 and SW480 cells.

Conclusions:

  • AP2 acts as a regulator of p21WAF1/CIP1 expression.
  • AP2 links differentiation processes to negative control of the cell cycle and cell growth.
  • These findings suggest AP2 plays a critical role in development through p21 activation.

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