c-Jun targets amino terminus of androgen receptor in regulating androgen-responsive transcription.
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.
Bubulya
A
A
Department of Biology, University of Toledo, OH 43606, USA.
Zhou
X F
XF
Shen
X Q
XQ
Fisher
C J
CJ
Shemshedini
L
L
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D015153:Blotting, Western; D019556:COS Cells; D004247:DNA / Q000378:metabolism; D004262:DNA Restriction Enzymes; D004268:DNA-Binding Proteins; D004347:Drug Interactions; D004591:Electrophoresis, Polyacrylamide Gel; D005656:Fungal Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D051958:Nuclear Receptor Coactivator 2; D010446:Peptide Fragments / Q000235:genetics / Q000502:physiology; D016133:Polymerase Chain Reaction; D016755:Proto-Oncogene Proteins c-jun / Q000494:pharmacology*; D011944:Receptors, Androgen / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology*; D011993:Recombinant Fusion Proteins; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000235:genetics / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection
D000728:Androgens; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; C498001:NCOA2 protein, human; D051958:Nuclear Receptor Coactivator 2; D010446:Peptide Fragments; D016755:Proto-Oncogene Proteins c-jun; D011944:Receptors, Androgen; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D004247:DNA; D004262:DNA Restriction Enzymes