Genes belonging to the Jun and Fos oncogene families encode nuclear proteins that are associated with a number of transcriptional complexes. The c-Jun protein is a major component of the transcription factor AP-1, originally shown to mediate phorbol ester tumor promoter (TPA)-induced expression of responsive genes through the TPA-response element (TRE). The Jun proteins form homo- and heterodimers which bind the TRE, while Fos proteins are active only as heterodimers with any of the Jun proteins. Fos/Jun heterodimers have a much higher affinity for the TRE than Jun homodimers. Ha-Ras augments c-Jun activity and stimulates phosphorylation of its activation domain. An inhibitor of Fos/Jun function, termed IP-1, associates with Fos and Jun and is inactivated upon phosphorylation induced by the cAMP-dependent protein kinase A (PKA).
