Differentiation-dependent activation of interferon-stimulated gene factors and transcription factor NF-kappa B in mouse embryonal carcinoma cells.
We have recently shown that the adenovirus E1A gene products block interferon-alpha-induced signal transduction and transcription factor NF-kappa B-mediated gene induction. Here we report that the same responses are also blocked in undifferentiated F9 teratocarcinoma cells. The block was removed upon cellular differentiation and regained upon the introduction of viral E1A into the differentiated cells. In undifferentiated cells, interferon-beta failed to induce the transcription of interferon-responsive genes because of a lack of activation of the cognate trans-acting factors. As a result, in these cells, virus replication was not inhibited by interferon. Similarly, in undifferentiated but not in differentiated F9 cells, tumor necrosis factor alpha failed to stimulate NF-kappa B-mediated transcription of a reporter gene because of a failure in the activation of NF-kappa B trans-acting factor. These results suggest that a cellular E1A-like activity, present in undifferentiated F9 cells, and adenoviral E1A use similar mechanisms for repressing the expression of specific cellular genes.
Kalvakolanu
D V
DV
Department of Molecular Biology, Cleveland Clinic Foundation, OH 44195-5285.
Sen
G C
GC
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis / Q000235:genetics; D000256:Adenoviridae / Q000235:genetics; D017500:Adenovirus E1A Proteins / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016899:Interferon-beta / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D013724:Teratoma; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*; D015533:Transcriptional Activation; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D017500:Adenovirus E1A Proteins; D016328:NF-kappa B; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D014212:Tretinoin; D016899:Interferon-beta; D007371:Interferon-gamma; D015500:Chloramphenicol O-Acetyltransferase; D015088:2',5'-Oligoadenylate Synthetase; D013755:Tetradecanoylphorbol Acetate