FRA-2 PROMOTER CAN RESPOND TO SERUM-STIMULATION THROUGH AP-1 COMPLEXES

fra-2 (fos-related antigen-2) expression is detected at a basal level even in growth-arrested chicken embryo fibroblasts (CEF), but upon ser um-stimulation high levels of its transcripts are transiently observed . This induction is delayed and prolonged compared to that of c-fos. T ransient expression experiments in CEF using a series of constructs of chicken fra-2 promoter region linked to the CAT reporter gene indicat ed previously that serum response element (SRE) is not required for fu ll serum inducibility. In this report, we show that constructs in whic h the CRE-Like sequence and both AP-1 binding sites are disrupted lack serum inducibility, suggesting that either of these enhancers is impo rtant in serum induction of fra-2. In growth-arrested CEF, small amoun ts of Fra-2/c-Jun complex bind to the AP-1 consensus sequences in fra- 2 promoter, while a significant part of the enhanced AP-1 binding acti vity after 60-120 min of serum stimulation is attributable to c-Fos/c- Jun heterodimer. At later times Fra-2/c-Jun again becomes the main com plex. Transient expression assays in F9 cells indicated that c-Fos/c-J un heterodimers have strong stimulatory effects on fra-2 promoter acti vity, while Fra-2/c-Jun complex has lower transcriptional activity tha n that of c-Jun homodimer. These results suggest that c-Fos (induced a t earlier times) and c-Jun proteins are at least partly responsible fo r serum-induced expression of fra-2.