title: Epstein-Barr virus antagonizes the antiproliferative activity of transforming growth factor-beta but does not abolish its signaling.
abstract: 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.
authors.affiliation: Institute of Clinical Molecular Biology and Tumor Genetics, GSF-Research Center for Environment and Health, Munich, Germany.
authors.forename: Manuela
authors.initials: M
authors.lastname: Horndasch
authors.forename: Eva E
authors.initials: EE
authors.lastname: Raschke
authors.forename: Guido
authors.initials: G
authors.lastname: Bommer
authors.forename: Marino
authors.initials: M
authors.lastname: Schuhmacher
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Dumont
authors.forename: Conny
authors.initials: C
authors.lastname: Kuklik-Roos
authors.forename: Dirk
authors.initials: D
authors.lastname: Eick
authors.forename: Bettina
authors.initials: B
authors.lastname: Kempkes
mesh_terms: 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
chemical_list: C402641:EBNA-2 protein, Human herpesvirus 4; D019309:Epstein-Barr Virus Nuclear Antigens; D016212:Transforming Growth Factor beta; D014764:Viral Proteins