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


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.

SUBMITTER: Shore AM 

PROVIDER: S-EPMC1642148 | biostudies-literature | 2006 Nov

REPOSITORIES: biostudies-literature

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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 AM   White Paul C PC   Hui Rosaline C-Y RC   Essafi Abdelkader A   Lam Eric W-F EW   Rowe Martin M   Brennan Paul P  

Journal of virology 20060830 22


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 downregulati  ...[more]

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