BCL3 Encodes a Nuclear Protein Which Can Alter the Subcellular Location of NF-κB Proteins

Abstract

BCL3 is a candidate proto-oncogene involved in the recurring translocation t(14;19) found in some patients with chronic lymphocytic leukemia. BCL3 protein acts as an IκB in that it can specifically inhibit the DNA binding of NF-kB factors. Here, we demonstrate that BCL3 is predominantly a nuclear protein and provide evidence that its N terminus is necessary to direct the protein into the nucleus. In contrast to IkBcα (MAD3), BCL3 does not cause NF-kB p50 to be retained in the cytoplasm; instead, in cotransfection assays, it alters the subnuclear localization of p50. The two proteins colocalize, suggesting that they interact in vivo. Further immunofluorescence experiments showed that a mutant p50, lacking a nuclear localization signal and restricted to the cytoplasm, is brought into the nucleus in the presence of BCL3. Correspondingly, a wild-type p50 directs into the nucleus a truncated BCL3, which, when transfected alone, is found in the cytoplasm. We tested whether BCL3 could overcome the cytoplasmic retention of p50 by IkBα. Results from triple cotransfection experiments with BCL3, IkBα, and p50 implied that BCL3 can successfully compete with IkBα and bring p50 into the nucleus; thus, localization of NF-kB factors may be affected by differential expression of IkB proteins. These novel properties of BCL3 protein further establish BCL3 as a distinctive member of the IkB family.