Topic
BCL3
About: BCL3 is a research topic. Over the lifetime, 3 publications have been published within this topic receiving 210 citations. The topic is also known as: BCL4 & D19S37.
Papers
TL;DR: It is demonstrated that BCL3 is predominantly a nuclear protein and provided evidence that its N terminus is necessary to direct the protein into the nucleus, further establishing B CL3 as a distinctive member of the I kappa B family.
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 I kappa B in that it can specifically inhibit the DNA binding of NF-kappa B 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 I kappa B alpha (MAD3), BCL3 does not cause NF-kappa B 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 I kappa B alpha. Results from triple cotransfection experiments with BCL3, I kappa B alpha, and p50 implied that BCL3 can successfully compete with I kappa B alpha and bring p50 into the nucleus; thus, localization of NF-kappa B factors may be affected by differential expression of I kappa B proteins. These novel properties of BCL3 protein further establish BCL3 as a distinctive member of the I kappa B family.
120 citations
Journal Article•
TL;DR: The results indicate a specific role for the putative I kappa B delta and suggest a possible mechanism of how the truncation of the ankyrin domain of p100, found in a number of lymphoid neoplasias, might contribute to tumorigenesis.
Abstract: The Rel/NF-kappa B family transcriptional factors plays an important role in the regulation of immune and acute phase responses. The activity of Rel/NF-kappa B complexes is regulated by their interactions with members of the I kappa B family of inhibitors. We have previously shown that the RelB/p52 heterodimer is not effectively inhibited by any of the known I kappa B molecules: I kappa B alpha, I kappa B gamma and Bcl3. Here we report that the C-terminal domain of p100 (the putative I kappa B delta) functions as a strong inhibitor of RelB/p52 transcriptional activity. In vivo interaction with I kappa B delta leads to the cytoplasmic retention and decreased DNA binding activity of RelB/p52 complexes. Thus, I kappa B delta is the only I kappa B molecule able to efficiently modulate the activity of RelB/p52 heterodimer. In Daudi cells, a 46 kD protein, probably representing the C-terminal product of the proteolytic processing of p100, remains associated with Rel/NF-kappa B complexes and might have a transient regulatory function. Our results indicate a specific role for the putative I kappa B delta and suggest a possible mechanism of how the truncation of the ankyrin domain of p100, found in a number of lymphoid neoplasias, might contribute to tumorigenesis.
91 citations
Journal Article•
TL;DR: It is proposed that I kappa B alpha and bcl3 can act as repressors or antirepressors of NF-kappa B-induced gene expression and can displace preformed DNA-protein complexes.
Abstract: The activity of the rel/NF-kappa B/dorsal family of kappa B site binding proteins is regulated by I kappa B proteins. The ankyrin repeat motif identified I kappa B family members, which include I kappa B alpha (pp40/MAD-3), I kappa B gamma, and bcl3, directly associated with kappa B site binding proteins, resulting in specific DNA-binding inhibition of rel, p50, or p65 dimers. We report that I kappa B gamma, containing eight ankyrin repeats, mediates a reversible inhibition of (p50)2-DNA complex but cannot displace preformed DNA-protein complexes. I kappa B alpha and bcl3, on the other hand, can displace preformed DNA-protein complexes. I kappa B alpha specifically displaces (p65)2 or p50/p65-DNA complexes but requires the C-terminal 37 amino acids in addition to the ankyrin repeat domain. Human bcl3 protein specifically displaces (p50)2-DNA complexes. Because I kappa B alpha and bcl3 can displace preformed (p65)2 or (p50)2-DNA complexes, respectively, we propose that they can act as repressors or antirepressors of NF-kappa B-induced gene expression.
18 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 1995 | 1 |
| 1994 | 1 |
| 1993 | 1 |