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- Title
Epstein-Barr virus-encoded latent infection membrane protein 1 regulates the processing of p100 NF-?B2 to p52 via an IKK?/NEMO-independent signalling pathway.
- Authors
Eliopoulos, Aristides G; Caamano, Jorge H; Flavell, Joanne; Reynolds, Gary M; Murray, Paul G; Poyet, Jean-Luc; Young, Lawrence S
- Abstract
The oncogenic Epstein-Barr virus (EBV)-encoded latent infection membrane protein 1 (LMP1) constitutively activates the ‘canonical’ NF-?B pathway that involves the phosphorylation and degradation of I?Ba downstream of the I?B kinases (IKKs). In this study, we show that LMP1 also promotes the proteasome-mediated proteolysis of p100 NF-?B2 resulting in the generation of active p52, which translocates to the nucleus in complex with the p65 and RelB NF-?B subunits. LMP1-induced NF-?B transactivation is reduced in nf-kb2-/- mouse embryo fibroblasts, suggesting that p100 processing contributes to LMP1-mediated NF-?B 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-?B pathway is impaired in cells lacking IKK?/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 IKK?. These data point to the existence of a novel signalling pathway that regulates NF-?B in LMP1-expressing cells, and may thereby play a role in both oncogenic transformation and the establishment of persistent EBV infection.Oncogene (2003) 22, 7557-7569. doi:10.1038/sj.onc.1207120
- Subjects
EPSTEIN-Barr virus; MEMBRANE proteins; ONCOGENIC DNA viruses; HERPESVIRUSES; BIOLOGICAL membranes
- Publication
Oncogene, 2003, Vol 22, Issue 48, p7557
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1207120