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NF-κB and IRF7 Pathway Activation by Epstein-Barr Virus Latent Membrane Protein 1
Division of Infectious Disease, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 28 May 2013; in revised form: 17 June 2013 / Accepted: 18 June 2013 / Published: 21 June 2013
Abstract: 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-κB, MAP kinase, IRF7, and PI3 kinase pathway stimulation. EBV-transformed B-cells are particularly dependent on constitutive NF-κB activity, and rapidly undergo apoptosis upon NF-κB blockade. Here, we review LMP1 function, with special attention to current understanding of the molecular mechanisms of LMP1-mediated NF-κB 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-κB and IRF7 pathway activation.
Keywords: herpesvirus; apoptosis; cancer; innate immunity; transformation; integral membrane protein; signal transduction; proliferation; ubiquitin; lymphoma; oncogene
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MDPI and ACS Style
Ersing, I.; Bernhardt, K.; Gewurz, B.E. NF-κB and IRF7 Pathway Activation by Epstein-Barr Virus Latent Membrane Protein 1. Viruses 2013, 5, 1587-1606.
Ersing I, Bernhardt K, Gewurz BE. NF-κB and IRF7 Pathway Activation by Epstein-Barr Virus Latent Membrane Protein 1. Viruses. 2013; 5(6):1587-1606.
Ersing, Ina; Bernhardt, Katharina; Gewurz, Benjamin E. 2013. "NF-κB and IRF7 Pathway Activation by Epstein-Barr Virus Latent Membrane Protein 1." Viruses 5, no. 6: 1587-1606.