scholarly journals Epstein-Barr virus latent membrane protein-2A-induced ΔNp63α expression is associated with impaired epithelial-cell differentiation

Oncogene ◽  
2010 ◽  
Vol 29 (30) ◽  
pp. 4287-4296 ◽  
Author(s):  
J A Fotheringham ◽  
S Mazzucca ◽  
N Raab-Traub
Keyword(s):  
Cell Differentiation ◽  
Epithelial Cell ◽  
Membrane Protein ◽  
Epstein Barr Virus ◽  
Latent Membrane Protein ◽  
Latent Membrane Protein 2A ◽  
Barr Virus ◽  
Epithelial Cell Differentiation ◽  
Epstein Barr ◽  
Virus Latent Membrane Protein

scholarly journals Roles of the ITAM and PY Motifs of Epstein-Barr Virus Latent Membrane Protein 2A in the Inhibition of Epithelial Cell Differentiation and Activation of β-Catenin Signaling

2005 ◽  
Vol 79 (4) ◽  
pp. 2375-2382 ◽  
Author(s):  
Jennifer A. Morrison ◽  
Nancy Raab-Traub
Keyword(s):  
Membrane Protein ◽  
Epstein Barr Virus ◽  
Nuclear Translocation ◽  
Cell Receptor ◽  
Latent Membrane Protein ◽  
Latent Membrane Protein 2A ◽  
Barr Virus ◽  
Cellular Processes ◽  
Epstein Barr ◽  
Virus Latent Membrane Protein

ABSTRACT Epstein-Barr virus (EBV) latent membrane protein 2A (LMP2A) is important for maintenance of latency in infected B lymphocytes. Through its immunoreceptor tyrosine-based activation motif (ITAM) and PY motifs, LMP2A is able to block B-cell receptor (BCR) signaling, bind BCR-associated kinases, and manipulate the turnover of itself and these kinases via a PY-mediated interaction with the Nedd4 family of ubiquitin ligases. In epithelial cells, LMP2A has been shown to activate the phosphatidylinositol 3′-OH kinase/Akt and β-catenin signaling pathways. In the present study, the biological consequences of LMP2A expression in the normal human foreskin keratinocyte (HFK) cell line were investigated and the importance of the ITAM and PY motifs for LMP2A signaling effects in HFK cells was ascertained. The ITAM was essential for the activation of Akt by LMP2A in HFK cells, while both the ITAM and PY motifs contributed to LMP2A-mediated accumulation and nuclear translocation of the oncoprotein β-catenin. LMP2A inhibited induction of differentiation in an assay conducted with semisolid methylcellulose medium, and the PY motifs were critical for this inhibition. LMP2A is expressed in the EBV-associated epithelial malignancies nasopharyngeal carcinoma and gastric carcinoma, and these data indicate that LMP2A affects cellular processes that likely contribute to carcinogenesis.

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