Cell target genes of Epstein-Barr virus transcription factor EBNA-2:: induction of the p55α regulatory subunit of PI3-kinase and its role in survival of EREB2.5 cells

Microarray analysis covering most of the annotated RNAs in the human genome identified a panel of genes induced by the Epstein-Barr virus (EBV) EBNA-2 transcription factor in the EIREB2.5 human B-lymphoblastoid cell line without the need for any intermediate protein synthesis. Previous data indicating that PIK3R1 RNA (the alpha regulatory subunit of PI3-kinase) was induced were confirmed, but it is now shown that it is the p55 alpha regulatory subunit that is induced. Several EBV-immortalized lymphoblastoid cell lines were shown to express p55 alpha. Expression of PI3-kinase p85 regulatory and p110 catalytic subunits was not regulated by EBNA-2. Proliferation of EREB2.5 lymphoblastoid cells was inhibited by RNAi knock-down of p55 alpha protein expression, loss of p55 alpha being accompanied by an increase in apoptosis. p55 alpha is thus a functional target of EBNA2 in EREB2.5 cells and the specific regulation of p55 alpha by EBV will provide an opportunity to investigate the physiological function of p55 alpha in this human cell line.