CHARACTERIZATION OF AN IMMEDIATE-EARLY GENE INDUCED IN ADHERENT MONOCYTES THAT ENCODES I-KAPPA-B-LIKE ACTIVITY

We have cloned a group of cDNAs representing mRNAs that are rapidly induced following adherence of human monocytes. One of the induced transcripts (MAD-3) encodes a protein of 317 amino acids with one domain containing five tandem repeats of the cdc 10/ankyrin motif, which is 60% similar (46% identical) to the ankyrin repeat region of the precursor of NF-kappa-B/KBF1 p50. The C-terminus has a putative protein kinase C phosphorylation site. In vitro translated MAD-3 protein was found to specifically inhibit the DNA-binding activity of the p50/p65 NF-kappa-B complex but not that of the p50/p50 KBF1 factor or of other DNA-binding proteins. The MAD-3 cDNA encodes an I-kappa-B-like protein that is likely to be involved in regulation of transcriptional responses to NF-kappa-B, including adhesion-dependent pathways of monocyte activation.