Repression of the interferon signal transduction pathway by the adenovirus E1A oncogene.
The signal transduction pathway initiated by type I interferon (alpha and beta interferons) is inhibited by expression of the adenovirus type 5 E1A oncogene. Cotransfection analyses with the E1A oncogene and an interferon-stimulated reporter gene show that mutations within an amino-terminal domain of the E1A oncoprotein are defective in transcriptional repression. Cotransfection experiments also revealed that the transcriptional repression is mediated through the interferon-stimulated response element (ISRE) found within the promoter of interferon-stimulated genes. Since interferon treatment activates a latent cytoplasmic DNA-binding factor that can recognize the ISRE and subsequently stimulate transcription, the appearance of this factor was analyzed in a cell line that constitutively expresses the E1A oncogene. The DNA binding activity of this transcriptional activator was found to be inhibited in the E1A-expressing cell line. In vitro cytoplasmic mixing experiments with extracts from control and E1A-expressing cells identified a specific component of this multimeric transcription factor to be defective.
Gutch
M J
MJ
Department of Pathology, State University of New York, Stony Brook 11794.
Reich
N C
NC
D017456:Adenovirus Early Proteins; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular; D004268:DNA-Binding Proteins / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000502:physiology*; D008113:Liver Neoplasms; D009841:Oligonucleotides / Q000737:chemistry; D009856:Oncogene Proteins, Viral / Q000502:physiology*; D012045:Regulatory Sequences, Nucleic Acid; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D017456:Adenovirus Early Proteins; D004268:DNA-Binding Proteins; D007370:Interferon Type I; D009841:Oligonucleotides; D009856:Oncogene Proteins, Viral; D014157:Transcription Factors