Positive and negative regulation of transcription in vitro: enhancer-binding protein AP-2 is inhibited by SV40 T antigen

Cell. 1987 Sep 11;50(6):847-61. doi: 10.1016/0092-8674(87)90512-5.


We have purified a 52 kd protein, AP-2, that binds to enhancer regions of SV40 and human metallothionein IIA (hMT IIA) and stimulates RNA synthesis from these promoters in vitro. Surprisingly, AP-2 also binds to two SV40 early promoter regions recognized by Sp1 and T antigen. Juxtaposed binding sites for AP-2 and Sp1 in the 21 bp repeats may facilitate productive interactions between the two factors. In contrast, sequence-specific binding of AP-2 to SV40 and hMT IIA DNA is inhibited by the viral repressor protein T antigen. Furthermore, T antigen inhibits AP-2-dependent transcriptional activation of the hMT IIA promoter in vitro. The inhibition is neither a direct nor an indirect result of T antigen binding to DNA, because the hMT IIA promoter lacks T antigen binding sites. Instead, sedimentation studies suggest that protein-protein interactions between AP-2 and T antigen block AP-2 binding to DNA. These findings suggest novel mechanisms for mediating positive and negative regulation of transcription.

Publication types

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

MeSH terms

  • Antigens, Polyomavirus Transforming
  • Antigens, Viral, Tumor / pharmacology*
  • Base Sequence
  • Binding Sites
  • DNA, Viral / genetics
  • DNA, Viral / metabolism
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / isolation & purification*
  • DNA-Binding Proteins / metabolism
  • Enhancer Elements, Genetic*
  • Gene Expression Regulation*
  • Genes, Regulator*
  • Genes, Viral
  • Humans
  • Metallothionein / genetics
  • Models, Genetic
  • Oncogene Proteins, Viral / pharmacology*
  • Promoter Regions, Genetic
  • Protein Binding / drug effects
  • Simian virus 40 / genetics*
  • Simian virus 40 / immunology
  • Transcription Factor AP-2
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / isolation & purification*
  • Transcription Factors / metabolism
  • Transcription, Genetic / drug effects


  • Antigens, Polyomavirus Transforming
  • Antigens, Viral, Tumor
  • DNA, Viral
  • DNA-Binding Proteins
  • Oncogene Proteins, Viral
  • Transcription Factor AP-2
  • Transcription Factors
  • Metallothionein