c-Jun targets amino terminus of androgen receptor in regulating androgen-responsive transcription

Endocrine. 2000 Aug;13(1):55-62. doi: 10.1385/ENDO:13:1:55.

Abstract

The human androgen receptor (hAR) is a member of the nuclear receptor superfamily and functions as a ligand-inducible transcription factor. We have previously proposed that c-Jun mediates the transcriptional activity of this receptor. The modular nature of hAR was used in this study to generate several fusions with the heterologous DNA-binding domain of the yeast transcription factor GAL4 in an attempt to identify the c-Jun-responsive domains within the receptor. Our results suggest that the target of c-Jun action is the amino terminus (AB region) of the receptor and that hAR amino acids 502-521 are critical for the c-Jun response. Additionally, amino acids 503-555 were shown to harbor an autonomous transactivation that is stimulated by c-Jun. Furthermore, we demonstrated that transcription intermediary factor-2 (TIF-2), a coactivator that acts on the activation function-2, stimulates the full-length hAR. These results suggest that c-Jun and TIF-2 can work together as coactivators on the hAR by targeting distinct portions of the receptor.

MeSH terms

  • Androgens / pharmacology*
  • Animals
  • Binding Sites
  • Blotting, Western
  • COS Cells
  • DNA / metabolism
  • DNA Restriction Enzymes
  • DNA-Binding Proteins
  • Drug Interactions
  • Electrophoresis, Polyacrylamide Gel
  • Fungal Proteins / genetics
  • Gene Expression Regulation*
  • Humans
  • Nuclear Receptor Coactivator 2
  • Peptide Fragments / genetics
  • Peptide Fragments / physiology
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins c-jun / pharmacology*
  • Receptors, Androgen / chemistry
  • Receptors, Androgen / drug effects*
  • Receptors, Androgen / physiology*
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins*
  • Transcription Factors / genetics
  • Transcription Factors / pharmacology
  • Transcription, Genetic / drug effects*
  • Transfection

Substances

  • Androgens
  • DNA-Binding Proteins
  • Fungal Proteins
  • GAL4 protein, S cerevisiae
  • NCOA2 protein, human
  • Nuclear Receptor Coactivator 2
  • Peptide Fragments
  • Proto-Oncogene Proteins c-jun
  • Receptors, Androgen
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • DNA
  • DNA Restriction Enzymes