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RESEARCH PAPER

Expression of the Bcl-3 proto-oncogene suppresses p53 activation

¹ Curriculum in Genetics and Molecular Biology, ² Lineberger Comprehensive Cancer Center, and ³ Department of Biology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA

While Bcl-3 expression in cancer was originally thought to be limited to B-cell lymphomas with a 14;19 chromosomal translocation, more recent evidence indicates that expression of this presumptive oncoprotein is significantly more widespread in cancer. However, an oncogenic role for Bcl-3 has not been clearly identified. Experiments presented here indicate that Bcl-3 is inducible by DNA damage and is required for the induction of Hdm2 gene expression and the suppression of persistent p53 activity. Furthermore, constitutive expression of Bcl-3 suppresses DNA damage-induced p53 activation and inhibits p53-induced apoptosis through a mechanism that is at least partly dependent on the up-regulation of Hdm2. The results provide insight into a mechanism whereby altered expression of Bcl-3 leads to tumorigenic potential. Since Bcl-3 is required for germinal center formation, these results suggest functional similarities with the unrelated Bcl-6 oncoprotein in suppressing potential p53-dependent cell cycle arrest and apoptosis in response to somatic hypermutation and class switch recombination.

[Keywords: Apoptosis; Bcl-3; Hdm2; NF-B; p53]

Received July 5, 2005; revised version accepted November 17, 2005.

Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.1352206.

⁴ Corresponding author.
E-MAIL abaldwin{at}med.unc.edu; FAX (919) 966-0444.

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