TFII-I ENHANCES ACTIVATION OF THE C-FOS PROMOTER THROUGH INTERACTIONSWITH UPSTREAM ELEMENTS

The transcription factor TFII-I was initially isolated as a factor tha t can bind to initiator elements in core promoters. Recent evidence su ggests that TFII-I may also have a role in signal transduction. We hav e found that overexpression of TFII-I can enhance the response of the wild-type c-fos promoter to a variety of stimuli. This effect depends on the c-fos c-sis-platelet-derived growth factor-inducible factor bin ding element (SIE) and serum response element (SRE), There is no effec t of cotransfected TFII-I on the TATA box containing the c-fos basal p romoter. Three TFII-I binding sites can be found in c-fos promoter. Tw o of these overlap the c-fos SIE and SRE, and another is located just upstream of the TATA box. Mutations that distinguish between serum res ponse factor (SRF), STAT, and TFII-I binding to the c-fos SIE and SRE suggest that the binding of TFII-I to these elements is important for c-fos induction in conjunction with the SRF and STAT transcription fac tors, Moreover, TFII-I can form in vivo protein-protein complexes with the c-fos upstream activators SRF, STAT1, and STAT3, These results su ggest that TFII-I may mediate the functional interdependence of the c- fos SIE and SRE elements. In addition, the ras pathway is required for TFII-I to exert its effects on the c-fos promoter, and growth factor stimulation enhances tyrosine phosphorylation of TFII-I. These results indicate that TFII-I is involved in signal transduction as well as tr anscriptional activation of the c-fos promoter.