Fa. Larosa et al., DIFFERENTIAL REGULATION OF THE C-MYC ONCOGENE PROMOTER BY THE NF-KAPPA-B REL FAMILY OF TRANSCRIPTION FACTORS, Molecular and cellular biology, 14(2), 1994, pp. 1039-1044
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.