Proceedings of the National Academy of Sciences - PNAS, 1991-09, Vol.88 (17), p.7459-7463
1991
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Details
- Autor(en) / Beteiligte
- Titel
- Inhibition of Interferon-Inducible Gene Expression by Adenovirus E1A Proteins: Block in Transcriptional Complex Formation
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 1991-09, Vol.88 (17), p.7459-7463
- Ort / Verlag
- Washington, DC: National Academy of Sciences of the United States of America
- Erscheinungsjahr
- 1991
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Infection with wild-type adenovirus 5, but not with a mutant lacking the E1A gene, prevented the induction by interferon (IFN) α of chloramphenicol acetyltransferase (CAT) activity in HeLaM cell lines that had been permanently transfected with chimeric CAT reporter genes driven by the transcriptional regulatory regions of the IFN-responsive genes 561 and 6-16. Similar inhibition of IFN-inducible CAT activity was observed in cells that were cotransfected with the same reporter genes and plasmids expressing either the E1A 289- or 243-amino acid protein. These proteins also prevented the induction of CAT activity by IFN-γ from a cotransfected HLA-DRα-CAT gene. Experiments with E1A mutants mapped the inhibitory activity to amino acid residues 38-65 of these proteins. In a HeLa cell line permanently expressing the E1A 289-amino acid protein, the replication of vesicular stomatitis virus and encephalomyocarditis virus was not inhibited by IFN-α, suggesting a global blockade of IFN responses. In accord with this theory, induction of 561, 1-8, and (2'-5')oligoadenylate synthetase mRNAs by IFN was blocked in these cells at the transcriptional level. The observed transcriptional inhibition could be attributed to the lack of formation of the crucial IFN-stimulated gene factor 3 (ISGF3) transcriptional complex. As shown by mobility shift assays, this complex was not formed in the nuclear extracts of IFN-treated adenovirus-infected cells or IFN-treated E1A-producing cells. These nuclear extracts were deficient in both ISGF3α and ISGF3γ subunits. However, they did not block the formation of ISGF3 complex from exogenously added components.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.88.17.7459Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_52319
- Format
- –
- Schlagworte
- 550200 - Biochemistry, ADENOVIRUS, Adenovirus Early Proteins, Adenoviruses, Adenoviruses, Human - genetics, Adenoviruses, Human - metabolism, alpha -interferon, BASIC BIOLOGICAL SCIENCES, BETA DECAY RADIOISOTOPES, BETA-MINUS DECAY RADIOISOTOPES, BIOCHEMISTRY, Biological and medical sciences, BIOLOGICAL EFFECTS, Blotting, Northern, CELL CONSTITUENTS, Cell extracts, Cell lines, Cell nucleus, Cell Transformation, Viral, CHEMISTRY, Chimera, Chloramphenicol O-Acetyltransferase - genetics, Chloramphenicol O-Acetyltransferase - metabolism, DAYS LIVING RADIOISOTOPES, E1A protein, ENZYME INDUCTION, ENZYMES, Fundamental and applied biological sciences. Psychology, Gene expression, Gene Expression - drug effects, GENE RECOMBINATION, GENE REGULATION, Genes, Genetic Vectors, GROWTH FACTORS, HELA CELLS, HeLa Cells - physiology, Humans, Infections, INHIBITION, INTERFERON, Interferon Type I - pharmacology, interferon-stimulated gene factors, ISOTOPES, Kinetics, LIGHT NUCLEI, LYMPHOKINES, Messenger RNA, MICROORGANISMS, MITOGENS, Molecular and cellular biology, Molecular genetics, NUCLEI, NUCLEIC ACIDS, ODD-ODD NUCLEI, OLIGONUCLEOTIDES, Oncogene Proteins, Viral - genetics, Oncogene Proteins, Viral - metabolism, ONCOGENIC VIRUSES, ORGANIC COMPOUNDS, PARASITES, PHOSPHORUS 32, PHOSPHORUS ISOTOPES, PLASMIDS, PROTEINS, RADIOISOTOPES, TRANSCRIPTION, Transcription Factors - metabolism, Transcription, Genetic - drug effects, Transfection, TRANSFERASES, Vesicular stomatitis Indiana virus - drug effects, Vesicular stomatitis Indiana virus - genetics, Vesicular stomatitis Indiana virus - physiology, Virus Replication - drug effects, VIRUSES