SYNERGISTIC STIMULATION OF AVIAN I-KAPPA-B-ALPHA TRANSCRIPTION BY RELAND FOS JUN FACTORS/

Rel/NF-kappa B transcription factors and I kappa B alpha function in a n autoregulatory network. Avian I kappa B alpha transcription is incre ased in response to both c-Rel and v-Rel. This study shows that I kapp a B alpha transcription is synergistically stimulated by Rel and AP-1 factors (c-Fos and c-Jun). However, the response to v-Rel and the AP-1 factors was not as vigorous as that of c-Rel and AP-1. A 386 bp regio n of the I kappa B alpha promoter (containing two NF-kappa B and one A P-1 binding sites) was shown to be both necessary and sufficient for r esponse to both Rel factors alone or Rel factors in conjunction with t he AP-1 proteins. In addition, an imperfect NF-kappa B binding site wa s found to overlap the AP-1 binding site. Mutation of either of the NF -kappa B binding sites or the AP-1 binding site dramatically decreased the response of the I kappa B alpha promoter to Rel proteins alone or Rel and AP-1 factors. Overexpression of c-Rel or v-Rel resulted in th e formation of DNA binding complexes associated with the imperfect NF- kappa B binding site which overlaps the AP-1 site. v-Rel associated wi th the imperfect NF-kappa B site stronger than c-Rel, and overexpressi on of v-Rel also resulted in the formation of a v-Rel containing compl ex bound to a consensus AP-1 site. These studies address the differenc e in c-Rel and v-Rel's ability to synergistically stimulate I kappa B alpha expression in conjunction with the AP-1 factors.