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 language | English |
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Pages (from-to) | 11191-9 |
Number of pages | 9 |
Journal | Journal of Virology |
Volume | 80 |
Issue number | 22 |
DOIs | |
Publication status | Published - 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