The oncoprotein Bcl-3 can facilitate NF-kappa B-mediated transactivation by removing inhibiting p50 homodimers from select kappa B sites.

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作者：

G Franzoso，V Bours，V Azarenko，S Park，M Tomita-Yamaguchi，T Kanno，K Brown，U Siebenlist

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摘要：

Previously we have proposed a role for Bcl-3 in facilitating transactivation through kappa B sites by counteracting the inhibitory effects of bound, non-transactivating homodimers of the subunit of NF-kappa B. Such homodimers are abundant for example in nuclei of unstimulated primary T cells. Here we extend the model and provide new evidence which fulfills a number of predictions. (i) Bcl-3 preferentially targets homodimers over NF-kappa B heterodimers since the homodimers are completely dissociated from kappa B sites at concentrations of Bcl-3 which do not affect NF-kappa B. (ii) Select kappa B sites associate very strongly and stably with homodimers, completely preventing by NF-kappa B. Such kappa B sites are likely candidates for regulation by homodimers and Bcl-3. (iii) Bcl-3 and can be co-localized in the , a requirement for active removal of homodimers from their sites in vivo. (iv) The ankyrin repeat domain of Bcl-3 is sufficient for the reversal of homodimer-mediated inhibition, correlating with the ability of this domain alone to inhibit to kappa B sites in vitro. Our data support the model that induction of nuclear Bcl-3 may be required during cellular stimulation to actively remove stably bound homodimers from certain kappa B sites in order to allow transactivating NF-kappa B complexes to engage. This exact mechanism is demonstrated with in vitro experiments.

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关键词：

Animals Ankyrins/metabolism Binding Sites Cell Nucleus/metabolism DNA/metabolism Fluorescent Antibody Technique NF-kappa B/metabolism Proto-Oncogene Proteins/metabolism Repetitive Sequences, Nucleic Acid Transcription Factors