NF-KAPPA-B PRECURSOR P100 INHIBITS NUCLEAR TRANSLOCATION AND DNA-BINDING OF NF-KAPPA-B/REL-FACTORS

The NF-kappaB precursor p100 (lyt-10, p97, p98) generates after proteolytic processing a 52 kDa subunit, which can bind to kappaB-motifs. A deregulated form of the p100 gene, which is structurally altered by a t(10;14) translocation, has a potential oncogenic role in certain human B cell lymphomas. In this study p100 was analysed for its ability to interact with its own processing product p52, with p50, the product of the NF-kappaB precursor p105, and with other NF-kappaB/rel-proteins. As demonstrated by a combination of Western blot analysis, band shift analysis and indirect immunofluorescence labelling of transfected cells, p100 itself was localized in the cytoplasm and indiscriminately retained each co-expressed NF-kappaB subunit. Thereby it simultaneously inhibited their DNA binding activities. Thus, a major function of p100 is, like p105, to associate with subunits of the rel multigene family in the cytoplasm in an IkappaB-like fashion. The similarity between p100 and p105 is also reflected by equivalent protein interactions of their processing products: like NF-kappaB-p50, also NF-kappaB-p52 heteromerised promiscuously with all rel-factors tested. Moreover, p52 efficiently interacts with the candidate oncogene product Bcl-3 and also binds to the basic-leucine zipper protein NF-IL6.