c-Jun Can Mediate Androgen Receptor-induced Transactivation

Abstract

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. 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.