Transcriptional induction of p69 2'-5'-oligoadenylate synthetase by interferon-alpha is stimulated by 12-O-tetradecanoyl phorbol-13-acetate through IRF/ISRE binding motifs.
Protein kinase C (PKC) is required for transcriptional induction of 2'-5'-oligoadenylate (2-5A) synthetases by interferon (IFN)-alpha. Regulatory elements located in the 5'-flanking region of the p69 2-5A synthetase gene have been identified which are required for transcriptional stimulation by PKC. The region from -366 to -117 bp, relative to the translational start site, contains three sequence motifs that resemble interferon stimulated response elements/interferon regulatory factor elements (ISRE/IRF-E), which are required for stimulation of the IFN-alpha-response by the PKC activator, 12-O-tetradecanoyl phorbol-13-acetate (TPA). Constructs which have a deletion of the region containing IRF-Es located at -361 bp to -280 and at -246 to -172 bp do not respond to TPA treatment. Likewise, introduction of point mutations into either of these IRF-Es decreases stimulation of IFN-alpha induction by TPA and constructs containing point mutations in both upstream IRF-Es are nonresponsive to TPA. Binding of the inducible factor to the ISRE is abrogated in cells depleted of PKC by prolonged treatment with TPA. PKC appears to function as a signaling component in an IFN-independent pathway that increases the activity of IFN-alpha-regulated transcription factors in the nucleus.
Yu
F
F
Molecular and Cellular Biology Program, Arizona State University, Tempe 85287-1501, USA.
Wang
Q
Q
Floyd-Smith
G
G
D015088:2',5'-Oligoadenylate Synthetase / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D020816:Amino Acid Motifs; D001665:Binding Sites; D002457:Cell Extracts; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D050835:Interferon Regulatory Factors; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016898:Interferon-alpha / Q000378:metabolism* / Q000494:pharmacology; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000378:metabolism; D011994:Recombinant Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000187:drug effects*; D050794:STAT1 Transcription Factor; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection; D000099185:Interferon Regulatory Factor-8
D015088:2',5'-Oligoadenylate Synthetase; D002457:Cell Extracts; D004268:DNA-Binding Proteins; D050835:Interferon Regulatory Factors; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016898:Interferon-alpha; D011493:Protein Kinase C; D011994:Recombinant Proteins; D012097:Repressor Proteins; D050794:STAT1 Transcription Factor; D013755:Tetradecanoylphorbol Acetate; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D000099185:Interferon Regulatory Factor-8; C494227:IRF9 protein, human; C494079:STAT1 protein, human