THE 65-KDA SUBUNIT OF HUMAN NF-KAPPA-B FUNCTIONS AS A POTENT TRANSCRIPTIONAL ACTIVATOR AND A TARGET FOR V-REL-MEDIATED REPRESSION

Molecular cloning of the polypeptide component of the Rel-related human p75 nucleoprotein complex has revealed its identity with the 65-kDa (p65) subunit of NF-kappa-B. Functional analyses of chimeric proteins composed of NF-kappa-B p65 C-terminal sequences linked to the DNA-binding domain of the yeast GAL4 polypeptide have indicated that the final 101 amino acids of NF-kappa-B p65 comprise a potent transcriptional activation domain. Transient transfection of human T cells with an expression vector encoding NF-kappa-B p65, but not NF-kappa-B p50, produced marked transcriptional activation of a basal promoter containing duplicated kappa-B enhancer motifs from the long terminal repeat of type 1 human immunodeficiency virus. These stimulatory effects of NF-kappa-B p65 were synergistically enhanced by coexpression of NF-kappa-B p50 but were completely inhibited by coexpression of the v-rel oncogene product. Together, these functional studies demonstrate that NF-kappa-B p65 is a transactivating subunit of the heterodimeric NF-kappa-B complex and serves as one cellular target for v-Rel-mediated transcriptional repression.