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TY - JOUR AU - Eliopoulos, Aristides G AU - Caamano, Jorge H AU - Flavell, Joanne AU - Reynolds, Gary M AU - Murray, Paul G AU - Poyet, Jean-Luc AU - Young, Lawrence S PY - 2003 DA - 2003/10/01 TI - Epstein–Barr virus-encoded latent infection membrane protein 1 regulates the processing of p100 NF-κB2 to p52 via an IKKγ/NEMO-independent signalling pathway JO - Oncogene SP - 7557 EP - 7569 VL - 22 IS - 48 AB - The oncogenic Epstein–Barr virus (EBV)-encoded latent infection membrane protein 1 (LMP1) constitutively activates the ‘canonical’ NF-κB pathway that involves the phosphorylation and degradation of IκBα downstream of the IκB kinases (IKKs). In this study, we show that LMP1 also promotes the proteasome-mediated proteolysis of p100 NF-κB2 resulting in the generation of active p52, which translocates to the nucleus in complex with the p65 and RelB NF-κB subunits. LMP1-induced NF-κB transactivation is reduced in nf-kb2−/− mouse embryo fibroblasts, suggesting that p100 processing contributes to LMP1-mediated NF-κB transcriptional effects. This pathway is likely to operate in vivo, as the expression of LMP1 in primary EBV-positive Hodgkin's lymphoma and nasopharyngeal carcinoma biopsies correlates with the nuclear accumulation of p52. Interestingly, while the ability of LMP1 to activate the canonical NF-κB pathway is impaired in cells lacking IKKγ/NEMO, the regulatory subunit of the IKK complex, p100 processing remains unaffected. As a result, nuclear translocation of p52, but not p65, occurs in the absence of IKKγ. These data point to the existence of a novel signalling pathway that regulates NF-κB in LMP1-expressing cells, and may thereby play a role in both oncogenic transformation and the establishment of persistent EBV infection. SN - 1476-5594 UR - https://doi.org/10.1038/sj.onc.1207120 DO - 10.1038/sj.onc.1207120 ID - Eliopoulos2003 ER -