Nucleic Acids Research, 1991, Vol. 19, No. 20 5537-5542
© 1991
MOLECULAR BIOLOGY |
Difference in transcriptional regulatory function between c-Fos and Fra-2
Department of Tumor Virus-Research, Institute of Medical Science, UNiversity of Tokyo 4–6–1 Shirokanedai, Minto-ku, Tokyo 108, Japan
*To whom corespondence should be addressed
Received July 25, 1991. Accepted September 26, 1991.
Fra-2, one of the Fos-related antigens, is promptly expressed after the growth stimulation of fibroblasts, but its induction peak is later than that of c-Fos. In this report, we examined biochemical properties of Fra-2 and compared them with those of two other Fos family proteins, c-Fos and Fra-1. Like c-Fos and Fra-1, Fra-2 formed stable heterodimers with c-Jun, JunB or JunD in vitro and all these complexes had specific DNAbinding activity to AP-1-binding sites (AP-1 sites) or related sequences. When transiently introduced into a mouse embryonic carcinoma cell line, F9, with reporter genes containing the AP-1 site from the collagenase gene, fra-2 plus c-jun suppressed the transactivation by c-jun alone. This property of Fra-2 is in clear contrast to that of c-Fos, which stimulates the transcriptional activity of c-Jun by forming a stable heterodimer. Analysis of chimeric proteins between c-Fos and Fra-2 indicated that this difference is mainly attributable to heir C terminal-half regions. Interestingly, this suppressive effect of Fra-2 was not observed in the combination with JunD: fra-2 plus junD, like c-fos plus junD, had higher ranscriptional activity than junD lone. Fra-1 showed essentially the same transcriptional regulatory properties as Fra-2. These differential properties greatly expand the potential range of regulatory functions of the Fos family proteins.
+Present address: Department of life sceince, facultyy of Biosceince and Biochemistry, Tokyo Institute of Technology, Nagatsuda, Midori-ku, Yokama 227, Japan
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