The candidate proto-oncogene bcl-3 encodes a transcriptional coactivator that activates through NF-kappa B p50 homodimers.

Abstract

The candidate proto-oncogene bcl-3 encodes a protein that shares structural features with IKB-~ and other proteins that bind to members of the Rel protein family. Here, we show that in contrast to the inhibitory activity of IKB-a, the bcl-3 gene product superactivates NF-KB p50 homodimer-mediated gene expression both in vivo and in vitro. BCL-3 protein can, as well, selectively associate with p50 homodimers in the presence of DNA containing a KB motif. These results strongly suggest that BCL-3 can act as a transcriptional coactivator, acting through DNA-bound pS0 homodimers.[Key Words: NF-KB; p50; IKB; transcription; coactivator]Received January 8, 1993; revised version accepted May 21, 1993.The candidate proto-oncogene bcl-3 was identified by the cloning of chromosomal breakpoints from chronic lymphocytic leukemia cells containing a t(14;19) translocation (Ohno et al. 1990). bcl-3 expression is activated by translocation without apparent alteration of the encoded protein structure. The deduced primary structure of BCL-3 contains seven repeats of an -30-amino-acid motif (ankyrin repeat) found in several other proteins (Nolan and Baltimore 1992). These include erythrocyte ankyrin, a cytoskeletal protein; yeast cell cycle regulatory proteins, such as cdclO and SWI6; and the transmembrane receptors notch, TAN1, and int-3.

Nuclear factor-κB and inhibitor of κB kinase pathways in oncogenic initiation and progression

“…Generally, the IkB proteins sequester the interacting NF-kB dimeric complexes in the cytoplasm, and therefore the ability of NF-kB to bind DNA and regulate gene expression is blocked. It should be noted that Bcl-3 is unusual in that it does not induce cytoplasmic retention, but rather positively regulates gene expression by acting as a transcriptional co-activator for NF-kB p50 and p52 homodimers in the nucleus on DNA (Fujita et al, 1993;Westerheide et al, 2001).…”

Mutations in the NF-κB signaling pathway: implications for human disease

“…Bcl-3 is a constitutively nuclear protein, has transcriptional activation domains and can associate with p50 and p52 homodimers to act as a transcriptional coactivator (Bours et al, 1993;Fujita et al, 1993;Dechend et al, 1999). As such, overexpression of BCL-3 is expected to result in increased transcription of genes normally regulated by p52 or p50 homodimers.…”

Sprouty4 negatively regulates protein kinase C activation by inhibiting phosphatidylinositol 4,5-biphosphate hydrolysis

“…The NF-kB luciferase assay using NF-kB-responsive promoter-luciferase reporter gene, a generous gift from Dr T Fujita (The Tokyo Metropolitan Institute of Medical Science, Japan), has been described (Fujita et al, 1993). Briefly, 5 Â 10 4 HEK293T cells were seeded onto 24-well plates on the day before transfection.…”