Roles of Stat1, Stat2, and interferon regulatory factor-9 (IRF-9) in interferon tau regulation of IRF-1.
Interferon tau (IFNtau) is the pregnancy recognition signal produced by the conceptus trophectoderm and acts in a paracine manner on the ovine endometrium to increase expression of IFN-stimulated genes primarily in the stroma and deep glandular epithelium, including IFN regulatory factor-1 (IRF-1). The roles of Stat1, Stat2, and IRF-9 in IFNtau regulation of IRF-1 expression were determined using human stromal fibroblasts lacking specific IFN signaling components or complemented with specific Stat1 mutants. In parental (2fTGH) cells treated with IFNtau, Stat1alpha/beta was tyrosine phosphorylated by 15 min, and IRF-1 mRNA and protein increased from 0 to 6 h, was maximal at 6 h, and decreased to 24 h. In contrast, IFNtau did not affect IRF-1 expression in Stat1- and Stat2-deficient cells or in Stat1-deficient cells complemented with Stat1 Y701Q or Stat1 R602L mutants. In Stat1-deficient cells complemented with the Stat1 S727A mutant, Stat1alpha, or Stat1beta and treated with IFNtau, IRF-1 increased from 0 to 6 h, was maximal at 6 h, and decreased thereafter. In IRF-9-deficient cells stimulated with IFNtau, IRF-1 increased from 0 to 6 h but did not exhibit the sharp decline from 6 to 12 h observed in other cells. Collectively, results indicate that IFNtau effect on IRF-1 expression is primarily regulated by tyrosine-phosphorylated Stat1alpha or Stat1beta dimers, whereas the decline of IRF-1 after 6 h of IFNtau treatment is regulated by IRF-9.
Stewart
M David
MD
Center for Animal Biotechnology and Genomics, Department of Animal Science, Texas A&M University, College Station, Texas 77843, USA.
Choi
Youngsok
Y
Johnson
Greg A
GA
Yu-Lee
Li-yuan
LY
Bazer
Fuller W
FW
Spencer
Thomas E
TE
D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D005347:Fibroblasts; D006801:Humans; D007202:Indicators and Reagents; D050856:Interferon Regulatory Factor-1; D007370:Interferon Type I / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D011257:Pregnancy Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism
D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; C494227:IRF9 protein, human; D007202:Indicators and Reagents; D050856:Interferon Regulatory Factor-1; D007370:Interferon Type I; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D010750:Phosphoproteins; D011257:Pregnancy Proteins; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050795:STAT2 Transcription Factor; C494084:STAT2 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C020947:interferon tau; D014443:Tyrosine