Transcriptional regulation of thec-jun proto-oncogen

The expression of c-jun proto-oncogene is rapidly and transiently induced when cultured cells are treated with many growth factors, serum, and phorbol esters. To understand how growth factors and serum regulate c-jun expression, I first studied the c-jun promoter by deletion and point mutational analysis and demonstrated that a consensus MEF2 site at $-$59 was responsible for serum and EGF induction of the promoter in HeLa cells. The c-jun MEF2 site was also sufficient for induction by EGF, serum, and phorbol esters when placed on a heterologous promoter. MEF2 site, found in many muscle-specific enhancers, are bound by a family of transcription factors, MEF2A through D, which are related to serum response factor (SRF) in their DNA binding domains. I have found that MEF2D is the predominant protein in HeLa cells that binds to the c-jun MEF2 site. When MEF2D was overexpressed in NIH3T3 cells containing low MEF2D activity, it reconstituted serum regulation of the MEF2 site in these cells. Deletion analysis of MEF2D showed that its DNA binding domain, when fused to a heterologous transcriptional activation domain, was sufficient for serum induction of the reporter gene containing a MEF2 site. This is the homologous domain to that in SRF which is required for serum induction of the c-fos serum response element, suggesting that serum regulation of c-fos and c-jun may share a common mechanism.