Journal
VIRUSES-BASEL
Volume 5, Issue 6, Pages 1587-1606Publisher
MDPI
DOI: 10.3390/v5061587
Keywords
herpesvirus; apoptosis; cancer; innate immunity; transformation; integral membrane protein; signal transduction; proliferation; ubiquitin; lymphoma; oncogene
Categories
Funding
- Burroughs Wellcome Career Award in Medical Sciences
- NCI [K08CA140780, RO1 CA085180]
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The principal Epstein-Barr virus (EBV) oncoprotein, Latent Membrane Protein 1 (LMP1), is expressed in most EBV-associated human malignancies. LMP1 mimics CD40 receptor signaling to provide infected cells with constitutive NF-kappa B, MAP kinase, IRF7, and PI3 kinase pathway stimulation. EBV-transformed B-cells are particularly dependent on constitutive NF-kappa B activity, and rapidly undergo apoptosis upon NF-kappa B blockade. Here, we review LMP1 function, with special attention to current understanding of the molecular mechanisms of LMP1-mediated NF-kappa B and IRF7 pathway activation. Recent advances include the elucidation of transmembrane motifs important for LMP1 trafficking and ligand-independent signaling, analysis of genome-wide LMP1 gene targets, and the identification of novel cell proteins that mediate LMP1 NF-kappa B and IRF7 pathway activation.
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