THE CANDIDATE ONCOPROTEIN BCL-3 IS AN ANTAGONIST OF P50/NF-KAPPA-B-MEDIATED INHIBITION

THE candidate oncogene bcl-3 was discovered as a translocation into the immunoglobulin alpha-locus in some cases of B-cell chronic lymphocytic leukaemias1. The protein Bcl-3 contains seven so-called ankyrin repeats. Similar repeat motifs are found in a number of diverse regulatory proteins but the motifs of Bcl-3 are most closely related to those found in I-kappa-B proteins in which the ankyrin repeat domain is thought to be directly involved in inhibition of NF-kappa-B activity. No biological function has yet been described for Bcl-3, but it was noted recently2 that Bcl-3 interferes with DNA-binding of the p50 subunit of NF-kappa-B in vitro. Here we demonstrate that Bcl-3 can aid kappa-B site-dependent transcription in vivo by counteracting the inhibitory effects of p50/NF-kappa-B homodimers. Bcl-3 may therefore aid activation of select NF-kappa-B-regulated genes, including those of the human immunodeficiency virus.