Nuclear factor of activated T cells (NFAT1-C) represses the enhancer II and pregenomic promoter (EnII/Cp) of hepatitis B virus (HBV) through its responsive site GGAGA and nullifies the HBx-driven transcriptional activation.
The immunosuppressant cyclosporin A (CsA)-sensitive nuclear factor of activated T cells 1 (NFAT1) has been known to be a transcriptional regulator of cytokine and viral genes during the immune response. By analyses of serial deletion, mutation, and heterologous promoter assay, we report here that the CsA-sensitive NFAT1-C represses the transcriptional activity of enhancer II and pregenomic promoter (EnII/Cp) of HBV through the NFAT1-C responsive site (GGAGA, nt 1603-1618) and nullifies the HBx-driven transcriptional activation of the EnII/Cp of HBV in a dose-dependent manner. These results suggest that a CsA-sensitive NFAT1-C may control the viral activity in HBV-infected cells by inhibiting the EII/Cp and nullifying the HBx-driven transcriptional activation.
Lee
J H
JH
School of Biological Sciences, Seoul National University, Korea.
Rho
H M
HM
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D019556:COS Cells; D002460:Cell Line; D016572:Cyclosporine / Q000494:pharmacology; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D006367:HeLa Cells; D006515:Hepatitis B virus / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015533:Transcriptional Activation; D054334:Viral Regulatory and Accessory Proteins
D004279:DNA, Viral; D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; C494006:NFATC2 protein, human; D009687:Nuclear Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D016572:Cyclosporine