title: Interferon-induced expression of different genes is mediated by distinct regulatory pathways.
abstract: Interferons (IFNs) regulate the expression of multiple genes and the regulatory sequences associated with several of these genes have been identified. How cell-surface IFN receptors communicate with such regulatory elements is as yet unknown. We have characterized the IFN responses of a mutant murine cell line (Ltk-aprt-) which is unable to mount an antiviral response when treated with IFN-beta. In contrast to its inability to activate antiviral pathways in these cells, IFN-beta inhibits their growth to the same level as observed in their parental L-929 line which is fully responsive to IFN, suggesting that distinct pathways account for antiviral and cytostatic responses. In agreement with this, Northern blot and nuclear run-on analyses show that the induction of transcription of three distinct genes (2,5(A) synthetase, BS-I-150, and BS-II-4) is blocked in Ltk-aprt- cells whereas another gene (I-8) is activated normally. Our results show that the defective responses observed in this cell line are not due to a nonfunctional IFN-beta cell-surface receptor and suggest that multiple pathways exist between the receptor and upstream gene regulatory elements.
authors: Department of Anatomy and Cell Biology, SUNY Health Science Center, Brooklyn 11203.
authors: B
authors: B
authors: Shan
authors: J A
authors: JA
authors: Lewis
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics; D000818:Animals; D015152:Blotting, Northern; D004247:DNA / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects*; D007372:Interferons / Q000494:pharmacology*; D007739:L Cells; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014762:Viral Interference
chemical_list: D012333:RNA, Messenger; D004247:DNA; D007372:Interferons; D015088:2',5'-Oligoadenylate Synthetase