THE C-JUN DELTA-DOMAIN INHIBITS NEUROENDOCRINE PROMOTER ACTIVITY IN ADNA-SEQUENCE-SPECIFIC AND PITUITARY-SPECIFIC MANNER

'The transcription and transformation activity of c-Jun is governed by a 27-amino acid regulatory motif, labeled the delta-domain, which is deleted in v-Jun. We have previously shown that c-jun is a potent inhi bitor of the rat prolactin (rPRL) promoter activity induced by either oncogenic Has or phorbol esters. Here, we have characterized the struc tural and cell-specific requirements for this c-Jun inhibitory respons e, and we show that this c-Jun inhibitory response mapped to the rPRL footprint II repressor site, was pituitary-specific and required the c -Jun delta-domain. Moreover, alteration of any one of these features ( e.g., cis-element, trans-factor, or cell-specific background) switched c-Jun to a transcriptional activator of the rPRL promoter. In HeLa no npituitary cells, c-Jun alone activated the rPRL promoter via the most proximal GHF-1/Pit-1 binding site, footprint I, and synergized with G HF-1. Finally, recombinant GHF-1 interacted directly with c-jun but no t c-Fos proteins. These data provide important fundamental insights in to the molecular mechanisms by which the c-Jun delta-domain functions as a modulatory switch and further imply that the functional role of c -Jun is dictated by cell-specific influences and the delta-domain moti f.