THE NF-KAPPA-B PRECURSOR P105 AND THE PROTOONCOGENE PRODUCT BCL-3 ARE I-KAPPA-B MOLECULES AND CONTROL NUCLEAR TRANSLOCATION OF NF-KAPPA-B

We have examined the interaction of the NF-kappaB precursor p105 with NF-kappaB subunits. Similar to an IkappaB molecule, p105 associates in the cytoplasm with p50 or p65. Through this assembly, p105 efficiently blocks nuclear transfer of either subunit. Moreover, the p105 protein inhibits DNA binding of dimeric NF-kappaB subunits in a similar, but not identical, manner to its isolated C-terminal domain, which contains an ankyrin-like repeat domain (ARD). The proto-oncogene product Bcl-3 also controls nuclear translocation of p50, but not of p65. Hence, p50 can be retained in the cytoplasm via at least three distinct interactions: through direct interactions either with its own precursor, with Bcl-3 or indirectly through IkappaBalpha or -beta when attached to p65. We discuss a function of p105 as a cytoplasmic assembly unit for homo- and heteromeric NF-kappaB complexes and of Bcl-3 as an IkappaB with novel subunit specificity.