Cell target genes of Epstein-Barr virus transcription factor EBNA-2: induction of the p55alpha 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 EREB2.5 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 p55alpha regulatory subunit that is induced. Several EBV-immortalized lymphoblastoid cell lines were shown to express p55alpha. 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 p55alpha protein expression, loss of p55alpha being accompanied by an increase in apoptosis. p55alpha is thus a functional target of EBNA2 in EREB2.5 cells and the specific regulation of p55alpha by EBV will provide an opportunity to investigate the physiological function of p55alpha in this human cell line.
Spender
Lindsay C
LC
Ludwig Institute for Cancer Research, University of Tokyo, Tokyo 113-8655, Japan.|Department of Virology, Imperial College Faculty of Medicine, Norfolk Place, London W2 1PG, UK.
Lucchesi
Walter
W
Department of Virology, Imperial College Faculty of Medicine, Norfolk Place, London W2 1PG, UK.
Bodelon
Gustavo
G
Ludwig Institute for Cancer Research, University of Tokyo, Tokyo 113-8655, Japan.|Department of Virology, Imperial College Faculty of Medicine, Norfolk Place, London W2 1PG, UK.
Bilancio
Antonio
A
Ludwig Institute for Cancer Research, University of Tokyo, Tokyo 113-8655, Japan.
Karstegl
Claudio Elgueta
CE
Ludwig Institute for Cancer Research, University of Tokyo, Tokyo 113-8655, Japan.|Department of Virology, Imperial College Faculty of Medicine, Norfolk Place, London W2 1PG, UK.
Asano
Tomoichiro
T
Department of Physiological Chemistry and Metabolism, University of Tokyo, Tokyo 113-8655, Japan.
Dittrich-Breiholz
Oliver
O
Institute of Pharmacology, Medical School Hannover, Carl Neuberg Strasse 1, D-30625 Hannover, Germany.
Kracht
Michael
M
Institute of Pharmacology, Medical School Hannover, Carl Neuberg Strasse 1, D-30625 Hannover, Germany.
Vanhaesebroeck
Bart
B
Department of Biochemistry and Molecular Biology, University College London, UK.|Ludwig Institute for Cancer Research, University of Tokyo, Tokyo 113-8655, Japan.
Farrell
Paul J
PJ
Ludwig Institute for Cancer Research, University of Tokyo, Tokyo 113-8655, Japan.|Department of Virology, Imperial College Faculty of Medicine, Norfolk Place, London W2 1PG, UK.
D017209:Apoptosis; D002460:Cell Line; D002470:Cell Survival; D004790:Enzyme Induction; D019309:Epstein-Barr Virus Nuclear Antigens / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D021122:Protein Subunits / Q000096:biosynthesis / Q000235:genetics; D034622:RNA Interference; D014157:Transcription Factors / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*
C402641:EBNA-2 protein, Human herpesvirus 4; D019309:Epstein-Barr Virus Nuclear Antigens; D021122:Protein Subunits; D014157:Transcription Factors; D014764:Viral Proteins; D019869:Phosphatidylinositol 3-Kinases