The oncoprotein Bcl-3 directly transactivates through kappa B motifs via association with DNA-binding p50B homodimers.
Bcl-3 is an I kappa B-related protein with ankyrin repeat motifs. Its gene is located at a site of recurrent translocations in a subset of B cell chronic lymphocytic leukemias. Bcl-3 associates tightly with p50B (NFKB2, p52) homodimers in cells, and together these proteins form a ternary complex with DNA at kappa B sites. Such an association functionally leads to a novel and potent form of transactivation through the kappa B motif: the tethering of Bcl-3 to DNA via the p50B homodimers allows Bcl-3 to transactivate directly, while p50B homodimers alone cannot. Transactivation mediated by Bcl-3 requires two cooperating domains located amino- and carboxy-terminal to the ankyrin domain. Bcl-3 is localized to the nucleus, and a Bcl-3-p50B complex is detected in certain lymphoid cells. Our data reveal a novel role for Bcl-3, distinct from that of the inhibitor I kappa B. The results have implications for tumorigenesis.
Bours
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V
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Franzoso
G
G
Azarenko
V
V
Park
S
S
Kanno
T
T
Brown
K
K
Siebenlist
U
U
D000818:Animals; D000081242:B-Cell Lymphoma 3 Protein; D001665:Binding Sites; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D046911:Macromolecular Substances; D016328:NF-kappa B / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D015534:Trans-Activators; D014157:Transcription Factors; D014158:Transcription, Genetic
D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; D046911:Macromolecular Substances; D016328:NF-kappa B; D011498:Protein Precursors; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C072386:p50B-p97 protein, human; D004247:DNA