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 cells have identified a variety of trans-acting factors that bind to the IFN-stimulated response element (ISRE) whose role in gene expression remain unclear. The present investigation was undertaken to delineate the signal transduction pathway as well as to identify the transcription factors regulated by murine IFN-beta in L929 cells. Tyrosine kinase inhibitor, Genistein, abrogated gene induction and activation of transcription factors by IFN-beta. As early as 5 min after IFN-beta treatment, a transcription factor was activated in the cytoplasm which subsequently migrated into the nucleus. Anti-phosphotyrosine antibodies detected a specific transcription factor induced by mIFN-beta. Antibodies raised against human ISGF-3 subunit proteins p48, p84, p91 and p113 recognized this factor in the cytoplasm as well as in the nucleus of IFN-beta-treated L929 cells. An antibody raised against an oligopeptide of human p113 (residues 435-450) recognized the ISGF-3 complexes both in 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 sequence of these proteins.
Cancer Center, Medical College of Wisconsin, Milwaukee 53226.
D V
DV
Kalvakolanu
S B
SB
Mannino
A
A
Thornton
K
K
Ozato
E C
EC
Borden
D000818:Animals; D003429:Cross Reactions; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D019833:Genistein; D006367:HeLa Cells; D006801:Humans; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016899:Interferon-beta / Q000494:pharmacology*; D007529:Isoflavones / Q000494:pharmacology; D007739:L Cells; D051379:Mice; D010446:Peptide Fragments / Q000276:immunology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects*; D015533:Transcriptional Activation
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C494227:IRF9 protein, human; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; C494228:Isgf3g protein, mouse; D007529:Isoflavones; D010446:Peptide Fragments; D012333:RNA, Messenger; D014157:Transcription Factors; D016899:Interferon-beta; D019833:Genistein; D011505:Protein-Tyrosine Kinases