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Transcription of the RelB gene is regulated by NF-κB

Oncogene volume 20, pages 7722–7733 (2001)Cite this article

Abstract

RelA and RelB are two members of the NF-κB family that differ structurally and functionally. While RelA is regulated through its cytosolic localization by inhibitor proteins or IκB and not through transcriptional mechanisms, the regulation of RelB is poorly understood. In this study we demonstrate that stimuli (TNF or LPS) lead within minutes to the nuclear translocation of RelA, but require hours to result in the nuclear translocation of RelB. The delayed nuclear translocation of RelB correlates with increases in its protein synthesis which are secondary to increases in RelB gene transcription. RelA is alone sufficient to induce RelB gene transcription and to mediate the stimuli-driven increase in RelB transcription. Cloning and characterization of the RelB 5′ untranslated gene region indicates that RelB transcription is dependent on a TATA-less promoter containing two NF-κB binding sites. One of the NF-κB sites is primarily involved in the binding of p50 while the other one in the binding and transactivation by RelA and also RelB. Lastly, it is observed that p21, a protein involved in cell cycle control and oncogenesis known to be regulated by NF-κB, is upregulated at the transcriptional level by RelB. Thus, RelB is regulated at least at the level of transcription in a RelA and RelB dependent manner and may exert an important role in p21 regulation.

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Acknowledgements

The work in this manuscript was supported by NIH grant R01 #AI36076. The authors would like to thank Dr Amer Beg from Columbia University for providing us with the Rel+/− and Rel−/− MEF, Dr Nancy Rice of NCI-Frederick Cancer Research Center for the RelB antibody, Dr Wafik El-Deiry from the University of Pennsylvania for the p21 promoter construct, the members of Dr Paya's laboratory for the helpful discussions, and Teresa Hoff for assistance in preparing this manuscript.

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Authors and Affiliations

  1. Department of Experimental Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN 55905, Minnesota, USA

    Gary D Bren, Hiroko Miyoshi & Carlos V Paya

  2. Department of Immunology Mayo Clinic, Rochester, MN 55905, Minnesota, USA

    Gary D Bren, Nancie J Solan, Kevin N Pennington, Lori J Pobst & Carlos V Paya

  3. Division of Infectious Diseases, Mayo Clinic, Rochester, MN 55905, Minnesota, USA

    Carlos V Paya

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  1. Gary D Bren
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Correspondence to Carlos V Paya.

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Bren, G., Solan, N., Miyoshi, H. et al. Transcription of the RelB gene is regulated by NF-κB. Oncogene 20, 7722–7733 (2001). https://doi.org/10.1038/sj.onc.1204868

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