RESUMO
The Simian Virus 40 (SV40) small-t antigen (ST) plays an important role in driving cell proliferation, enhancing transformation by the large-T (LT) antigen. Potential targets of ST are the cyclin kinase inhibitor p27 and the cyclin A gene itself. Transactivation of the cyclin A promoter by ST depends on the interaction of ST with protein phosphatase 2A (PP2A) and occurs through a cell cycle-regulated E2F site near the transcription start site of the promoter. A third SV40 early protein, 17KT, also transactivates the cyclin A promoter but, in this case, transactivation depends on the dnaJ domain of the protein.
Assuntos
Antígenos Virais de Tumores/fisiologia , Proteínas de Ciclo Celular/metabolismo , Ciclo Celular/fisiologia , Ciclina A/genética , Proteínas de Ligação a DNA/metabolismo , Fosfoproteínas Fosfatases/metabolismo , Vírus 40 dos Símios/fisiologia , Fatores de Transcrição/metabolismo , Animais , Linhagem Celular , Chlorocebus aethiops , Fatores de Transcrição E2F , Humanos , Regiões Promotoras Genéticas , Proteína Fosfatase 2 , Ativação TranscricionalRESUMO
Epstein-Barr virus (EBV) latently infects and immortalizes B lymphocytes and causes lymphoproliferative malignancies. We show here that the EBV nuclear antigen EBNA2 induces expression of the 2 chains of the interleukin-18 receptor (IL-18R) in Burkitt lymphoma (BL) cell lines and in nontransformed B cells. Activation of IL-18R expression by EBNA2 is independent of its interaction with the transcriptional repressor RBPJ kappa. It occurs in the absence of any other viral protein but requires de novo synthesis of cellular proteins. IL-18R induction is a highly specific function of EBNA2, because neither other EBV latent proteins nor the cellular proteins c-myc or Notch can exert this effect. Using cDNA microarray expression profiling, we find that the IL-18 receptor expressed in EBV-infected BL cells has signaling capacity, because IL-18 significantly modified gene expression. We report that EBNA2 expression is associated with IL-18R expression in vivo in EBV-positive B-lymphomas from AIDS patients.