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 int erferon-alpha-induced signal transduction and transcription factor NF- kappaB-mediated gene induction. Here we report that the same responses are also blocked in undifferentiated F9 teratocarcinoma cells. The bl ock was removed upon cellular differentiation and regained upon the in troduction of viral E1A into the differentiated cells. In undifferenti ated cells, interferon-beta failed to induce the transcription of inte rferon-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 no t in differentiated F9 cells, tumor necrosis factor alpha failed to st imulate NF-kappaB-mediated transcription of a reporter gene because of a failure in the activation of NF-kappaB trans-acting factor. These r esults suggest that a cellular E1A-like activity, present in undiffere ntiated F9 cells, and adenoviral E1A use similar mechanisms for repres sing the expression of specific cellular genes.