Induction of AP-1 (Fos/Jun) by chemical agents mediates activation of glutathione S-transferase and quinone reductase gene expression

Oncogene. 1994 Feb;9(2):565-71.


A regulatory element, EpRE, was found to be responsible for the induction of mouse glutathione S-transferase (GST) Ya gene expression by a variety of chemical agents such as planar aromatic hydrocarbons, diphenols, phorbol ester, phenobarbital and electrophilic compounds. The EpRE is composed of two adjacent AP-1-like binding sites and was recently found to be activated by Fos/Jun heterodimeric complex (AP-1). In this report we show that regulatory elements ARE, previously demonstrated to mediate the chemical induction of rat GST Ya and quinone reductase genes, have a similar structure with EpRE and are activated by Fos/Jun complex. The activation of GST Ya and quinone reductase genes by a variety of chemical inducers is found to be associated with an increase in AP-1 binding activity. We present evidence that chemical agents induce expression of c-fos and c-jun proto-oncogenes and an enhanced synthesis of protein components of AP-1 complex. We suggest that the increased synthesis of AP-1 complex followed by an AP-1-mediated transcriptional activation of GST Ya and quinone reductase genes may provide a molecular mechanism for the induction of these drug-metabolizing enzymes by chemical agents.

Publication types

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

MeSH terms

  • Arsenates / pharmacology
  • Arsenites / pharmacology
  • Base Sequence
  • Binding Sites
  • Carcinoma, Embryonal / pathology
  • Carcinoma, Hepatocellular / pathology
  • Chlorides / pharmacology
  • Cycloheximide / pharmacology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics*
  • Genes, Regulator / genetics
  • Genes, fos / genetics
  • Genes, jun / genetics
  • Glutathione Transferase / genetics*
  • Humans
  • Hydrocarbons / pharmacology*
  • Hydrogen Peroxide / pharmacology
  • Molecular Sequence Data
  • Phenobarbital / pharmacology*
  • Phorbol Esters / pharmacology*
  • Proto-Oncogene Proteins c-jun / genetics*
  • Quinone Reductases / genetics*
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Transcription, Genetic / genetics
  • Transcriptional Activation / genetics
  • Tumor Cells, Cultured
  • Zinc Compounds / pharmacology


  • Arsenates
  • Arsenites
  • Chlorides
  • Hydrocarbons
  • Phorbol Esters
  • Proto-Oncogene Proteins c-jun
  • RNA, Messenger
  • Zinc Compounds
  • zinc chloride
  • Cycloheximide
  • Hydrogen Peroxide
  • Quinone Reductases
  • Glutathione Transferase
  • Phenobarbital