The c-Jun δ-domain inhibits neuroendocrine promoter activity in a DNA sequence- and pituitary-specific manner

Kathryn N. Farrow, Nicole Manning, Fred Schaufele, Arthur Gutierrez-Hartmann*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

The transcription and transformation activity of c-Jun is governed by a 27-amino acid regulatory motif, labeled the δ-domain, which is deleted in v- Jun. We have previously shown that c-Jun is a potent inhibitor of the rat prolactin (rPRL) promoter activity induced by either oncogenic Ras or phorbol esters. Here, we have characterized the structural and cell-specific requirements for this c-Jun inhibitory response, 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 δ-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 nonpituitary cells, c-Jun alone activated the rPRL promoter via the most proximal GHF-1/Pit-1 binding site, footprint I, and synergized with GHF-1. Finally, recombinant GHF-1 interacted directly with c-Jun but not c-Fos proteins. These data provide important fundamental insights into the molecular mechanisms by which the c-Jun δ-domain functions as a modulatory switch and further imply that the functional role of c-Jun is dictated by cell-specific influences and the δ-domain motif.

Original languageEnglish (US)
Pages (from-to)17139-17146
Number of pages8
JournalJournal of Biological Chemistry
Volume271
Issue number29
DOIs
StatePublished - 1996

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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