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Epstein-Barr virus represses the FoxO1 transcription factor through latent membrane protein 1 and latent membrane protein 2A

Shore, Angharad M., White, Paul Charles, Hui, Rosaline C.-Y., Essafi, Abdelkader, Lam, Eric W.-F., Rowe, Martin and Brennan, Paul 2006. Epstein-Barr virus represses the FoxO1 transcription factor through latent membrane protein 1 and latent membrane protein 2A. Journal of Virology 80 (22) , pp. 11191-11199. 10.1128/JVI.00983-06

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Abstract

Epstein-Barr virus (EBV) infection is associated with the development of many B-cell lymphomas, including Burkitt's lymphoma, Hodgkin's lymphoma, and posttransplant lymphoproliferative disease. The virus alters a diverse range of cellular molecules, which leads to B-cell growth and immortalization. This study was initiated to investigate the interplay between EBV and a proapoptotic transcription factor target, FoxO1. In this report, we show that EBV infection of B cells leads to the downregulation of FoxO1 expression by phosphatidylinositol 3-kinase-mediated nuclear export, by inhibition of FoxO1 mRNA expression, and by alteration of posttranslational modifications. This repression directly correlates with the expression of the FoxO1 target gene Bcl-6 and inversely correlates with the FoxO1-regulated gene Cyclin D2. Expression of the EBV genes for latent membrane protein 1 and latent membrane protein 2A decreases FoxO1 expression. Thus, our data elucidate distinct mechanisms for the regulation of the proapoptotic transcription factor FoxO1 by EBV.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Additional Information: Pdf uploaded in accordance with publisher's policy at http://www.sherpa.ac.uk/romeo/issn/0022-538X/ (accessed 25/02/2014)
Publisher: American Society for Microbiology
ISSN: 0022-538X
Date of First Compliant Deposit: 30 March 2016
Last Modified: 04 Jun 2017 01:31
URI: http://orca-mwe.cf.ac.uk/id/eprint/306

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