TRANSCRIPTIONAL INDUCTION OF GENES BY IFN-BETA IN MOUSE CELLS IS REGULATED BY A TRANSCRIPTION FACTOR SIMILAR TO HUMAN ISGF-3

Previous studies of IFN-stimulated transcription factors in murine cel ls have identified a variety of trans-acting factors that bind to the IFN-stimulated response element (ISRE) whose role in gene expression r emain unclear. The present investigation was undertaken to delineate t he signal transduction pathway as well as to identify the transcriptio n factors regulated by murine IFN-beta in L929 cells. Tyrosine kinase inhibitor, Genistein, abrogated gene induction and activation of trans cription factors by IFN-beta. As early as 5 min after IFN-beta treatme nt, a transcription factor was activated in the cytoplasm which subseq uently migrated into the nucleus. Anti-phosphotyrosine antibodies dete cted a specific transcription factor induced by mIFN-beta. Antibodies raised against human ISGF-3 subunit proteins p48, p84, p91 and p113 re cognized this factor in the cytoplasm as well as in the nucleus of IFN -beta-treated L929 cells. An antibody raised against an oligopeptide o f human p113 (residues 435-450) recognized the ISGF-3 complexes both i n human and murine cells. However, a different antibody against the C- terminus of human p113 (residues 671-806) did not recognize the ISGF-3 like complex in mouse cells, indicating differences in the primary se quence of these proteins.