c-Fos dimerization with c-Jun represses c-Jun enhancement of androgen receptor transactivation.
The transcriptional activity of the human androgen receptor (hAR), like other nuclear receptors, is dependent on accessory factors. One such factor is c-Jun, which has been shown to have a selective function of mediating androgen receptor-dependent transactivation. This c-Jun activity is inhibited by c-Fos, another protooncoprotein that can dimerize with c-Jun to form the transcription factor AP-1. Here we show that c-jun mediates hAR-induced transactivation from the promoter of the androgen-regulated gene, human kallikrein-2 (hKLK2), and c-Fos blocks this activity. Using c-Fos truncation mutants and measuring hKLK2-dependent transcription, we have determined that the bZIP region of c-Fos is required and sufficient for inhibiting c-Jun enhancement of hAR transactivation. Further truncation analysis of the bZIP shows that the c-Fos dimerization function, mediated through the leucine zipper, is essential for the negative activity, whereas DNA binding, mediated through the basic region, is dispensable. These results suggest that heterodimerization by c-Fos with c-Jun blocks c-Jun's ability to enhance hAR-induced transactivation.
Tillman
K
K
University of Toledo, Department of Biology, OH 43606-3390, USA.
Oberfield
J L
JL
Shen
X Q
XQ
Bubulya
A
A
Shemshedini
L
L
D000818:Animals; D019556:COS Cells; D004247:DNA / Q000378:metabolism; D019281:Dimerization; D006801:Humans; D007610:Kallikreins / Q000235:genetics; D016350:Leucine Zippers; D016760:Proto-Oncogene Proteins c-fos / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D016755:Proto-Oncogene Proteins c-jun / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000494:pharmacology; D015533:Transcriptional Activation; D014162:Transfection
D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011944:Receptors, Androgen; D018808:Transcription Factor AP-1; D004247:DNA; D007610:Kallikreins