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The bcl-3 proto-oncogene encodes a nuclear I kappa B-like molecule that preferentially interacts with NF-kappa B p50 and p52 in a phosphorylation-dependent manner

Nolan, Garry P. and Fujita, Takashi and Bhatia, Kishor and Huppi, Conrad and Liou, Hsiou-Chi and Scott, Martin L. and Baltimore, David (1993) The bcl-3 proto-oncogene encodes a nuclear I kappa B-like molecule that preferentially interacts with NF-kappa B p50 and p52 in a phosphorylation-dependent manner. Molecular and Cellular Biology, 13 (6). pp. 3557-3566. ISSN 0270-7306.

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The product of the putative proto-oncogene bcl-3 is an I kappa B-like molecule with novel binding properties specific for a subset of the rel family of transcriptional regulators. In vitro, Bcl-3 protein specifically inhibited the DNA binding of both the homodimeric NF-kappa B p50 subunit and a closely related homolog, p52 (previously p49), to immunoglobulin kappa NF-kappa B DNA motifs. Bcl-3 could catalyze the removal of these proteins from DNA. At concentrations that significantly inhibited DNA binding by homodimeric p50, Bcl-3 did not inhibit binding of reconstituted heterodimeric NF-kappa B (p50:p65), a DNA-binding homodimeric form of p65, or homodimers of c-Rel. Phosphatase treatment of Bcl-3 partially inactivated its inhibitory properties, implicating a role for phosphorylation in the regulation of Bcl-3 activity. Bcl-3, like p50, localizes to the cell nucleus. In cells cotransduced with Bcl-3 and p50, both molecules could be found in the nucleus of the same cells. Interestingly, coexpression of Bcl-3 with a p50 mutant deleted for its nuclear-localizing signal resulted in the relocalization of Bcl-3 to the cytoplasm, showing that the proteins interact in the cell. These properties contrast Bcl-3 to classically defined I kappa B, which maintains heterodimeric NF-kappa B p50:p65 in the cytoplasm through specific interactions with the p65 subunit. Bcl-3 appears to be a nuclear, I kappa B-related molecule that regulates the activity of homodimeric nuclear p50 and its homolog p52.

Item Type:Article
Baltimore, David0000-0001-8723-8190
Additional Information:Copyright © 1993 by the American Society for Microbiology. Received 9 December 1992/Returned for modification 1 January 1993/Accepted 2 March 1993 We thank members of the Baltimore laboratory for help and suggestions throughout the course of this project. We are grateful to Lawrence Kerr for sharing of data and discussions prior to publication. We thank Warren Pear for the sharing of data prior to publication (32a). G.P.N. is a Special Fellow of The Leukemia Society of America; H.-C.L. is a Fellow of the Cancer Research Institute. This work, and M.L.S. and T.F., are supported by grants CA51462 and GM39458 to D.B.
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Deposited On:18 Sep 2007
Last Modified:06 Nov 2017 23:05

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