Uncoiling c-Jun coiled coils: Inhibitory effects of truncated fos peptideson jun dimerization and DNA binding in vitro

c-Jun is an oncoprotein that comprises a portion of the AP-1 transcription factor and belongs to the basic-leucine zipper (bZIP) DNA binding protein f amily. Using peptides derived from the leucine zipper region of Fos, we hav e developed agents that inhibit Jun's DNA binding in the low micromolar ran ge. Fos peptides that were effective inhibitors in the DNA binding assay we re also found to inhibit cellular Jun binding to an AP-1 site in a lucifera se reporter plasmid in MCF-7 cells. Size exclusion studies confirmed that p eptides that inhibit the DNA binding of Jun also inhibit its dimerization. These peptides were found to have a cytotoxic effect on the MCF-7 cell line when delivered with the transfecting agent Tfx-50, possibly due to their r ole as transcription factor regulators. (C) 1998 John Wiley & Sons, Inc.