BCL3 ENCODES A NUCLEAR-PROTEIN WHICH CAN ALTER THE SUBCELLULAR LOCATION OF NF-KAPPA-B PROTEINS

BCL3 is a candidate proto-oncogene involved in the recurring transloca tion t(14;19) found in some patients with chronic lymphocytic leukemia . BCL3 protein acts as an I kappa KB in that it can specifically inhib it the DNA binding of NF-kappa B factors. Here, we demonstrate that BC L3 is predominantly a nuclear protein and provide evidence that its N terminus is necessary to direct the protein into the nucleus. In contr ast to I kappa B alpha (MAD3), BCL3 does not cause NF-KB p50 to be ret ained in the cytoplasm; instead, in cotransfection assays, it alters t he subnuclear localization of p50. The two proteins colocalize, sugges ting that they interact in vivo. Further immunofluorescence experiment s showed that a mutant p50, lacking a nuclear localization signal and restricted to the cytoplasm, is brought into the nucleus in the presen ce of BCL3. Correspondingly, a wild-type p50 directs into the nucleus a truncated BCL3, which, when transfected alone, is found in the cytop lasm. We tested whether BCL3 could overcome the cytoplasmic retention of p50 by I kappa B alpha. Results from triple cotransfection experime nts with BCL3, I kappa B alpha, and p50 implied that BCL3 can successf ully compete with I kappa B alpha and bring p50 into the nucleus; thus , localization of NF-kappa B factors may be affected by differential e xpression of I kappa B proteins. These novel properties of BCL3 protei n further establish BCL3 as a distinctive member of the I kappa B fami ly.