AVIAN I-KAPPA-B-ALPHA IS TRANSCRIPTIONALLY INDUCED BY C-REL AND V-RELWITH DIFFERENT KINETICS

The Rel/NF-kappa B family of transcription factors participates in the regulation of genes involved in defense responses, inflammation, heal ing and regeneration processes, and embryogenesis. The control of the transcriptional activation potential of the Rel/NF-kappa B proteins is mediated, in part, by their association with inhibitory proteins of t he I kappa B family. This association results in the cytoplasmic reten tion of these factors until the cell receives a proper stimulatory sig nal. The I kappa B alpha gene is a target for regulation by the Rel/NF -kappa B proteins and is in fact upregulated in response to Rel/NF-kap pa B activation. A naturally occurring oncogenic variant of the Rel/NF -kappa B family, v-rel, transforms avian lymphocytes, bone marrow cell s, monocytes, and fibroblasts. Avian I kappa B alpha expression is upr egulated in cells transformed by v-Rel. Avian I kappa B alpha is also upregulated in fibroblasts overexpressing c-Rel and oncogenic variants of c-Rel. c-Rel, a carboxy-terminally truncated variant of c-Rel, and v-Rel are all able to directly transactivate the expression of the av ian I kappa B alpha gene. However, c-Rel was the most potent activator of this gene, and the induction of I kappa B alpha expression showed faster kinetics in cells overexpressing c-Rel than in those overexpres sing v-Rel. The regulation of I kappa B alpha induction by the Rel pro teins nas shown to be dependent on a 362-bp region of the I kappa B al pha promoter that contains two potential NF-kappa B binding sites and one AP-l-like binding site. Results of electrophoretic mobility shift assays using these NF-kappa B binding sites indicate that major change s in the profile of DNA binding complexes in fibroblasts overexpressin g v-Rel correlated temporally with the kinetic changes in v-Rel's abil ity to activate the expression of the I kappa B alpha gene.