DIFFERENTIAL REGULATION OF THE C-MYC ONCOGENE PROMOTER BY THE NF-KAPPA-B REL FAMILY OF TRANSCRIPTION FACTORS

The murine c-myc gene contains two elements responsive to the rel-onco gene-related family of NF-kappa B factors. Previously we have shown th at factor binding to these two NF-kappa B elements mediates induction of transcription of the c-myc promoter upon interleukin-l treatment of human dermal fibroblasts and human T cell leukemia virus type I tax g ene expression in T cells (D. J. Kessler, M. P. Duyao, D. B. Spicer, a nd G. E. Sonenshein, J Exp. Med. 176:787-792, 1992; M. P. Duyao, D. J. Kessler, D. B. Spicer, C. Bartholomew, J. L. Cleveland, M. Siekevitz, and G. E. Sonenshein, J. Biol. Chem. 267:16288-16291, 1992). To begin to delineate the specific roles of the individual members of the NF-k appa B family, here we have tested their effects on activation of a c- myc promoter/exon 1-CAT construct in NIH 3T3 cells. Classical NF-kappa B (p65/p50) was a potent transcriptional activator of the c-myc promo ter. Cotransfection with either p65 alone or p65 in combination with p 50 mediated significant induction. In contrast, expression of either v -rel or chicken c-rel failed to transactivate, while murine c-rel indu ced c-myc promoter activity only slightly. Furthermore, induction by c lassical NF-kappa B was inhibited by coexpression of either v-rel or c hicken c-rel. Thus, individual members of the rel family have differen tial effects on the c-myc promoter, which can modulate overall transcr iptional activity and allow for precise regulation of this oncogene un der diverse physiologic conditions.