THE CHARACTERIZATION OF THE PROMOTER OF THE GENE ENCODING THE P50 SUBUNIT OF NF-KAPPA-B INDICATES THAT IT PARTICIPATES IN ITS OWN REGULATION

In order to characterize the regulation of the gene encoding the p50 subunit of the transcription factor NF-kappa-B, we have isolated a human genomic clone, and sequenced the promoter of this gene. By in situ hybridization we have mapped the gene encoding the p50 subunit of NF-kappa-B to the 4q23-4q25 region of the human genome and the H1-H3 region of the murine chromosome 3. The p50 promoter lacks TATA and CAAT elements, but contains NF-kappa-B, AP-1 and HIP-1 binding sequences. The kappa-B motif binds NF-kappa-B, KBF1, and heterodimers of p50 and c-rel, suggesting that the gene is regulated by members of this family. Cotransfection experiments demonstrate that the p50 promoter can be activated by either of the two subunits of NF-kappa-B (p50 and p65), and more strongly by the combination of both. The promoter of p50 can be activated by phorbol esters and tumor necrosis factor-alpha but not by forskolin and these responses are mediated through the NF-kappa-B binding sequence. The involvement of NF-kappa-B in the regulation of the p50 gene is also supported by the inhibition of the PMA activation of the promoter by an NF-kappa-B transdominant negative mutant, as well as by the product of the nu-rel oncogene.