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Lymphoma

RelA and RelB cross-talk and function in Epstein–Barr virus transformed B cells

Leukemia volume 28, pages 871–879 (2014)Cite this article

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Abstract

In this study, we determined the respective roles of RelA and RelB NF-κB subunits in Epstein–Barr virus (EBV)-transformed B cells. Using different EBV-immortalized B-cell models, we showed that only RelA activation increased both survival and cell growth. RelB activity was induced secondarily to RelA activation and repressed RelA DNA binding by trapping the p50 subunit. Reciprocally, RelA activation repressed RelB activity by increasing expression of its inhibitor p100. To search for such reciprocal inhibition at the transcriptional level, we studied gene expression profiles of our RelA and RelB regulatable cellular models. Ten RelA-induced genes and one RelB-regulated gene, ARNTL2, were repressed by RelB and RelA, respectively. Apart from this gene, RelB signature was included in that of RelA Functional groups of RelA-regulated genes were for control of energy metabolism, genetic instability, protection against apoptosis, cell cycle and immune response. Additional functions coregulated by RelA and/or RelB were autophagy and plasma cell differentiation. Altogether, these results demonstrate a cross-inhibition between RelA and RelB and suggest that, in fine, RelB was subordinated to RelA. In the view of future drug development, RelA appeared to be pivotal in both classical and alternative activation pathways, at least in EBV-transformed B cells.

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Acknowledgements

This work was supported by Institut National du Cancer, Cancéropôle Grand-Sud-Ouest, Comité Orientation Recherche Cancer du Limousin, Conseil Régional du Limousin, Comités Limousin de la Ligue contre le Cancer and Association pour la Recherche sur le Cancer. We thank the tumor banks of the University hospitals of Bordeaux and Limoges for providing biopsies and Véronique Pantesco (Microarray Core Facility of the Institute for Research in Biotherapy, Montpellier, France) for Affymetrix analyses. We thank Dr Jeanne Cook-Moreau, CNRS-UMR-7276 Limoges, for English corrections and Mr Lionel Forestier platform GENOLIM, University of Limoges, France. N Faumont was supported by Comité Orientation Recherche Cancer du Limousin, A Chanut and S Durand-Panteix by Association pour la Recherche sur le Cancer. A Chanut was also supported by Société Française d’Hématologie.

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  1. A Marfak

    Present address: 5Present address: Statistical Unit, IFCS (Institut de formation aux carrières de santé), Rabat, Morocco.,

Authors and Affiliations

  1. CNRS-UMR-7276, University of Limoges, and CHU Dupuytren, Laboratory of Hematology, Limoges, France

    A Chanut, F Duguet, A Marfak, A David, S Durand-Panteix, M Boulin-Deveza, N Gachard, I Youlyouz-Marfak, D Bordessoule, J Feuillard & N Faumont

  2. CHU Dupuytren, Laboratory of Pathology, Limoges, France

    B Petit

  3. CHU de Bordeaux, Laboratory of Pathology, Bordeaux, France

    M Parrens

  4. Department of Hematology, CHU Dupuytren, Limoges, France

    D Bordessoule

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Chanut, A., Duguet, F., Marfak, A. et al. RelA and RelB cross-talk and function in Epstein–Barr virus transformed B cells. Leukemia 28, 871–879 (2014). https://doi.org/10.1038/leu.2013.274

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