Interferon-tau (IFNtau) regulation of IFN-stimulated gene expression in cell lines lacking specific IFN-signaling components.
Interferon-tau (IFNtau) is a unique type I IFN secreted by the ruminant conceptus that acts in a paracrine manner on the endometrial epithelium to signal pregnancy recognition. In the ovine endometrium, IFNtau suppresses estrogen receptor alpha and oxytocin receptor gene expression, but increases or induces expression of IFN-simulated genes (ISGs), including signal transducer and activator of transcription-1 (STAT1), STAT2, ISG factor-3gamma (ISGF3gamma)/p48/IFN regulatory factor-9, and 2',5'-oligoadenylate synthetase (OAS). Human fibroblast cell lines lacking specific IFN signaling components were employed to determine the roles of STAT1, STAT2, and ISGF3gamma in the effects of IFNtau on ISG protein expression. Results indicated that STAT1alpha or STAT1beta is required for IFNtau effects on STAT2, ISGF3gamma, and OAS (40/46, 69/71, and 100 kDa). STAT2 is required for effects on STAT1, ISGF3gamma, and all OAS forms. ISGF3gamma is required for effects of IFNtau on STAT2 and 40/46- and 69/71-kDa OAS and plays a role in the effects of IFNtau on 100-kDa OAS and STAT1. Mutation of Tyr(701), but not Ser(727), of STAT1 abolished the effects of IFNtau on ISG expression. Mutation of the SH2 domain of STAT1 abolished the effects of IFNtau on all ISGs and reduced increases in 100-kDa OAS. These data illustrate the importance of transcription factors composed of STAT1, STAT2, and ISGF3gamma in the signaling pathway mediating the effects of IFNtau on ISG expression.
Stewart
M D
MD
Center for Animal Biotechnology and Genomics, Department of Animal Science, Texas A&M University, College Station, Texas 77843-2471, USA.
Johnson
G A
GA
Bazer
F W
FW
Spencer
T E
TE
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D010766:Phosphorylation; D011257:Pregnancy Proteins / Q000494:pharmacology*; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000096:biosynthesis / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; C494227:IRF9 protein, human; D007370:Interferon Type I; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D011257:Pregnancy Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050795:STAT2 Transcription Factor; C494084:STAT2 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C020947:interferon tau; D015088:2',5'-Oligoadenylate Synthetase