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  • Original Paper
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The Bcl-3 oncoprotein acts as a bridging factor between NF-κB/Rel and nuclear co-regulators

Abstract

The proto-oncoprotein Bcl-3 is a member of the IκB family and is present predominantly in the nucleus. To gain insight into specific nuclear functions of Bcl-3 we have isolated proteins that interact with its ankyrin repeat domain. Using the yeast two-hybrid-system we identified four novel binding partners of Bcl-3 in addition to NF-κB p50 and p52, previously known to associate with Bcl-3. The novel Bcl-3 interactors Jab1, Pirin, Tip60 and Bard1 are nuclear proteins which also bind to other transcription factors including c-Jun, nuclear factor I (NFI), HIV-1 Tat or the tumor suppressor and Polll holoenzyme component Brca1, respectively. Bcl-3, p50, and either Bard1, Tip60 or Pirin are sequestered into quarternary complexes on NF-κB DNA binding sites, whereas Jab1 enhances p50-Bcl-3-DNA complex formation. Furthermore, the histone acetylase Tip60 enhances Bcl-3-p50 activated transcription through an NF-κB binding site, indicating that quarternary complexes containing Bcl-3 interactors modulate NF-κB driven gene expression. These data implicate Bcl-3 as an adaptor between NF-κB p50/p52 and other transcription regulators and suggest that its gene activation function may at least in part be due to recruitment of the Tip60 histone actetylase.

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Abbreviations

ARD:

ankyrin repeat domain

Bard1:

Brca1 associated RING domain

BRCT:

Brca1 C-terminus

CBP:

CREB-binding protein

chromo:

chromatin organisation modifier

EMSA:

electrophoretic mobility shift assay

Jab1:

c-Jun activation domain binding protein

LTR:

long terminal repeat

RING:

zinc finger motif homologous to RING1 gene

Tip60:

Tat interacting protein 60 kDa

Traf2:

TNF-receptor associated factor 2

TRE:

TPA responsive element

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Acknowledgements

We thank Dr Richard Baer, Dallas, for providing full-length Bard1 and Brca1. This work was supported in part by grants from the Deutsche Forschungsgemeinschaft to RD (DE/631/1-1) and to CS (SFB344).

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Dechend, R., Hirano, F., Lehmann, K. et al. The Bcl-3 oncoprotein acts as a bridging factor between NF-κB/Rel and nuclear co-regulators. Oncogene 18, 3316–3323 (1999). https://doi.org/10.1038/sj.onc.1202717

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