Cellular target genes of Epstein-Barr virus nuclear antigen 2.
Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA-2) is a key determinant in the EBV-driven B-cell growth transformation process. By activating an array of viral and cellular target genes, EBNA-2 initiates a cascade of events which ultimately cause cell cycle entry and the proliferation of the infected B cell. In order to identify cellular target genes that respond to EBNA-2 in the absence of other viral factors, we have performed a comprehensive search for EBNA-2 target genes in two EBV-negative B-cell lines. This screen identified 311 EBNA-2-induced and 239 EBNA-2-repressed genes that were significantly regulated in either one or both cell lines. The activation of most of these genes had not previously been attributed to EBNA-2 function and will be relevant for the identification of EBNA-2-specific contributions to EBV-associated malignancies. The diverse spectrum of EBNA-2 target genes described in this study reflects the broad spectrum of EBNA-2 functions involved in virus-host interactions, including cell signaling molecules, adapters, genes involved in cell cycle regulation, and chemokines.
Maier
Sabine
S
GSF-National Research Center for Environment and Health, Institute of Clinical Molecular Biology, Munich, Germany.
Staffler
Gabriele
G
Hartmann
Andrea
A
Höck
Julia
J
Henning
Karen
K
Grabusic
Kristina
K
Mailhammer
Reinhard
R
Hoffmann
Reinhard
R
Wilmanns
Matthias
M
Lang
Roland
R
Mages
Jörg
J
Kempkes
Bettina
B
D001402:B-Lymphocytes / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics / Q000378:metabolism*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D019309:Epstein-Barr Virus Nuclear Antigens; D012333:RNA, Messenger; D051880:Receptors, Notch