IDENTIFICATION OF DOMAINS OF C-JUN MEDIATING ANDROGEN RECEPTOR TRANSACTIVATION

The proto-oncoprotein c-Jun, when complexed with c-Fos, forms the clim eric complex identified as AP-1 which regulates transcription directly by binding to AP-1-responsive genes. We have previously reported an i ndirect mechanism by which c-Jun is able to regulate transcription by stimulating androgen receptor transactivation in the absence of c-Fos or any apparent DNA binding. A series of c-Jun mutants were tested in order to characterize the domains of c-Jun responsible for this effect . The studies reported here indicate that functional bZIP region and a portion of the N-terminal activation functions is necessary for c-Jun stimulation of androgen receptor transactivation. Testing c-Jun/v-Jun chimeras, we show that v-Jun is unable to stimulate androgen receptor transactivation and the effect is dependent on the c-Jun activation f unctions, c-Jun exhibits a bell-shaped activity on androgen receptor-m ediated transactivation which appears to be distinct from c-Jun's tran sactivation ability. A c-Jun mutant deficient in transactivation is ab le to stimulate androgen receptor activity. These results indicate tha t c-Jun's transactivation ability can be separated from c-Jun's abilit y to stimulate the androgen receptor transactivation.