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

Angharad M Shore, Paul C White, Rosaline C-Y Hui, Abdelkader Essafi, Eric W-F Lam, Martin Rowe, Paul Brennan

Research output: Contribution to journalArticle (Academic Journal)peer-review

23 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)11191-9
Number of pages9
JournalJournal of Virology
Volume80
Issue number22
DOIs
Publication statusPublished - Nov 2006

Keywords

  • Burkitt Lymphoma
  • Cell Line, Tumor
  • Cyclin D2
  • Cyclins
  • DNA
  • DNA-Binding Proteins
  • Down-Regulation
  • Electrophoresis, Polyacrylamide Gel
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors
  • Herpesvirus 4, Human
  • Humans
  • Immunoblotting
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-bcl-6
  • RNA, Messenger
  • Statistics as Topic
  • Viral Matrix Proteins
  • Journal Article
  • Research Support, Non-U.S. Gov't

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