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

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.

Reversion of apoptotic resistance of TP53-mutated Burkitt lymphoma B-cells to spindle poisons by exogenous activation of JNK and p38 MAP kinases

“…19, 46 Assessment of mitochondrial potential with DiOC6(3) was performed as follows: 1  μ l DiOC6(3) solution (0.5  μ M in DMSO, Invitrogen, Fisher) was added to 500  μ l of cell suspension (2.5 × 10 5 cells) and incubated for 20 min at room temperature. Before flow cytometric analysis (on a FacsCalibur, Becton Dickinson, Franklin Lakes, NJ, USA), 1  μ l TOPRO-3 (1 mM, Invitrogen) was added to each sample.…”

Apoptosis- and survival-related gene mRNA profile in peripheral blood leukocytes in children with acute EBV infectious mononucleosis

“…Литературными данными подтверждаются ВЭБ-ассоциированные изменения некоторых сигнальных факторов (BID-Σ [44], RELA-Σ [10,11] и др. ).…”

Reproducing Transformation of Indolent B-cell Lymphoma by T-cell Immunosuppression of L.CD40 Mice

“…CD40 and LMP1 signaling pathways are not exactly similar (Graham et al, 2010). For example, CD40 activation of the alternate NF-κB pathway is more intense than the one of LMP1 that mainly activates the classical pathway (Chanut et al, 2014).…”