Epstein-Barr virus antagonizes the antiproliferative activity of transforming growth factor-beta but does not abolish its signaling.
TGF-beta induces apoptosis and inhibits the proliferation of EBV-negative B-lymphoma cell lines. In contrast, EBV-immortalized B cells are resistant to both the proapoptotic and the antiproliferative activities of TGF-beta. We have generated a lymphoblastoid cell line, in which we can switch on and off the EBV-specific transcriptional program driven by EBNA2. When these cells express the EBNA2-driven phenotype, they are resistant to TGF-beta-mediated growth arrest. We used this cell line to readdress the question of how EBV can overcome the antiproliferative TGF-beta activity. We show here that EBV-driven cells remain TGF-beta-responsive since TGF-beta target genes are readily induced. Thus, EBV can overcome TGF-beta-mediated growth arrest without interfering with the core machinery of the TGF-beta signaling pathway, which links ligand binding to the induction of TGF-beta target genes.
Horndasch
Manuela
M
Institute of Clinical Molecular Biology and Tumor Genetics, GSF-Research Center for Environment and Health, Munich, Germany.
Raschke
Eva E
EE
Bommer
Guido
G
Schuhmacher
Marino
M
Dumont
Elisabeth
E
Kuklik-Roos
Conny
C
Eick
Dirk
D
Kempkes
Bettina
B
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001402:B-Lymphocytes; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002472:Cell Transformation, Viral; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics / Q000502:physiology; D015967:Gene Expression Regulation, Viral; D016259:Genes, myc; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000502:physiology; D006801:Humans; D015398:Signal Transduction / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014764:Viral Proteins
C402641:EBNA-2 protein, Human herpesvirus 4; D019309:Epstein-Barr Virus Nuclear Antigens; D016212:Transforming Growth Factor beta; D014764:Viral Proteins