AP2 inhibits cancer cell growth and activates p21WAF1/CIP1 expression

Nat Genet. 1997 Jan;15(1):78-82. doi: 10.1038/ng0197-78.


The 52-kD Activator Protein (AP2) is a DNA-binding transcription factor implicated in signalling terminal differentiation. Profound developmental abnormalities have been recently observed in AP2-null mice. The molecular events by which AP2 promotes differentiation or development are, however, unknown. Increased expression of the universal cell cycle inhibitor p21WAF1/CIP1 occurs in growth-arrested terminally differentiating cells. In a search for cellular factors that could activate p21 during phorbol ester (TPA)-induced differentiation, we identified AP2 as a regulator of p21 expression. Mutagenesis of an AP2 DNA-binding site within a p21 promoter-luciferase reporter inhibited its activation by either AP2 transfection or TPA stimulation. Endogenous p21 protein levels were elevated and DNA synthesis was inhibited in AP2 versus control vector-transfected cells. Overexpression of AP2 in HepG2 human hepatoblastoma and SW480 human colon adenocarcinoma cells inhibited cell division and stable colony formation. These results link the differentiation-associated factor AP2 to negative cell cycle and growth control, possibly through p21 activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Division / physiology*
  • Chromosomes, Human, Pair 6
  • Cloning, Molecular
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / biosynthesis
  • Cyclins / genetics*
  • DNA-Binding Proteins / physiology*
  • Gene Expression Regulation*
  • Humans
  • Luciferases / genetics
  • Mutagenesis, Site-Directed
  • Promoter Regions, Genetic
  • Transcription Factor AP-2
  • Transcription Factors / physiology*
  • Tumor Cells, Cultured


  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • DNA-Binding Proteins
  • Transcription Factor AP-2
  • Transcription Factors
  • Luciferases