c-Jun can mediate androgen receptor-induced transactivation.
The proto-oncoprotein c-Jun forms as a heterodimer with c-Fos, the transcription factor AP-1. AP-1 regulates transcription through transactivation, a process requiring DNA binding. Here we report an indirect mechanism by which c-Jun can regulate transcription via the androgen receptor. In this process, c-Jun is able to support androgen receptor-mediated transactivation in the absence of an interaction with c-Fos or any apparent DNA binding. This positive effect of c-Jun was dose-dependent. Both exogenously added and endogenously induced c-Jun are able to act on the androgen receptor. Transactivation by the androgen receptor can undergo self-squelching, and this was relieved by transfected c-Jun. Using a time-course experiment, we provide evidence that the c-Jun effect is primary. c-Fos is able to block human androgen receptor activity in both the absence and presence of transfected c-Jun. Using a modified form of the yeast two-hybrid system, we show in Cos cells that c-Jun can interact with the DNA binding domain/hinge region (CD regions) of the androgen receptor. Therefore, we propose that c-Jun functions as a mediator for androgen receptor-induced transactivation.
Bubulya
A
A
Department of Biology, University of Toledo, Toledo, Ohio 43606, USA.
Wise
S C
SC
Shen
X Q
XQ
Burmeister
L A
LA
Shemshedini
L
L
D000818:Animals; D019556:COS Cells; D006801:Humans; D011485:Protein Binding; D016760:Proto-Oncogene Proteins c-fos / Q000502:physiology; D016755:Proto-Oncogene Proteins c-jun / Q000037:antagonists & inhibitors / Q000502:physiology*; D011944:Receptors, Androgen / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology*
D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011944:Receptors, Androgen