Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor

Cell. 1987 Jun 19;49(6):729-39. doi: 10.1016/0092-8674(87)90611-8.


The promoter regions of several phorbol diester-(TPA-) inducible genes (collagenase, stromelysin, hMT IIA, and SV40) share a conserved 9 bp motif. Synthetic copies of these closely related sequences conferred TPA inducibility upon heterologous promoters. Footprinting analysis indicated that these TPA-responsive elements (TREs) are recognized by a common cellular protein: the previously described transcription factor AP-1. A point mutation that eliminated the basal and induced activity of the TRE also interfered with its ability to bind AP-1. Treatment of cultured cells with TPA led to a rapid 3- to 4-fold increase in TRE binding activity, by a posttranslational mechanism. These results strongly suggest that AP-1 is at the receiving end of a complex pathway responsible for transmitting the effects of phorbol ester tumor promoters from the plasma membrane to the transcriptional machinery.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding Sites
  • DNA-Binding Proteins / genetics*
  • Endopeptidases / genetics
  • Enhancer Elements, Genetic*
  • Gene Expression Regulation / drug effects*
  • Genes, Regulator*
  • Humans
  • Matrix Metalloproteinase 3
  • Metallothionein / genetics
  • Microbial Collagenase / genetics
  • Promoter Regions, Genetic*
  • Rats
  • Simian virus 40 / genetics
  • Tetradecanoylphorbol Acetate / pharmacology*
  • Transcription Factors / genetics*


  • DNA-Binding Proteins
  • Transcription Factors
  • Metallothionein
  • Endopeptidases
  • Matrix Metalloproteinase 3
  • Microbial Collagenase
  • Tetradecanoylphorbol Acetate