BACKGROUND: Human cytomegalovirus (HCMV) has the ability to activate the expression of many viral and cellular genes. The c-jun proto-oncogene has known to be induced at immediate early time of HCMV infection, however, the mechanism of up-regulation of the gene was not known. We found HCMV immediate-early (IE) 2 expression transactivate the c-jun promoter in human embryonal lung cell (HEL). METHODS: The c-jun promoter region between -117 and -59 contains binding sites for the transcription factors Sp1, CAAT, AP-1 like (ATF/CREB), and MEF2. We tried to map the sequences in the c-jun promoter responsible for activation of the promoter by HCMV IE2 expression. Transient expression assays were performed using various reporter plasmids containing the c-jun promoter-regulatory region linked to the luciferase gene and a plasmid expressing HCMV IE2 gene. RESULTS: Deletional and point mutational analysis showed that ATF, MEF2, and another down stream elements were involved in the up-regulation of c-jun promoter. Gel mobility shift assay showed that there are several factors in HEL cell nuclear extracts that specifically bind to these sites and in vitro translated IE2 could not move or supershift the specific bands. CONCLUSION: This study delineate the mechanism of c-jun up-regulation in HCMV infection and would give the clue for the possible contribution of HCMV in tumorigenesis.