Critical role of the transcription factor AP-1 for the constitutive and interferon-induced expression of IFI 16.
IFI 16 is a member of the HIN-200 family of transcriptional regulators that suppress cell growth, modulate the cell cycle and have been linked to cellular differentiation. We hypothesized that the activity of IFI 16 depends on its level of expression and therefore studied the transcriptional activity of the IFI 16 promoter. A discrete sequence within the 5' untranslated region was required for constitutive activity of the promoter and the functional motif within this region was shown to be a consensus AP-1 site. Interestingly, this AP-1 site was also critical for IFN-induced activation of the promoter and consistent with these observations, treatment of cells with IFNgamma resulted in a rapid and robust induction of AP-1 activity that preceded expression of IFI 16. These experiments define the transcriptional mechanisms of IFI 16 gene regulation and provide evidence suggesting that AP-1 activation may be an important event in IFN signaling.
Clarke
C J P
CJ
Trescowthick Research Laboratories, Peter MacCallum Cancer Institute, St. Andrews Place, East Melbourne, Victoria 3002, Australia.
Apostolidis
V
V
Hii
L L P
LL
Gough
D J
DJ
Trapani
J A
JA
Johnstone
R W
RW
D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011506:Proteins / Q000235:genetics*; D011994:Recombinant Proteins; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; D011994:Recombinant Proteins; D018808:Transcription Factor AP-1; C076700:IFI16 protein, human; D007371:Interferon-gamma; D004247:DNA; D013755:Tetradecanoylphorbol Acetate