The promoter of human p22/PACAP response gene 1 (PRG1) contains functional binding sites for the p53 tumor suppressor and for NFkappaB.
We describe functional binding sites for the tumor suppressor p53 and for NFkappaB residing in the promoter of the novel human early response gene p22/PRG1 (IEX-1/DIF-2). Gel shift and supershift assays demonstrate binding of p53 and NFkappaB to their corresponding sites in vitro. CAT-reporter gene assays show transactivation of the human p22/PRG1 promoter by p53 in Hep3B cells stably transfected with a temperature-sensitive mutant p53, but not in p53-deficient Hep3B cells. TNF alpha induced NFkappaB dependent transactivation was shown in HepG2 cells or in 818-4 pancreatic cancer cells. These data imply that human p22/PRG1 is a target gene for p53 and NFkappaB involved in growth regulation and stress response.
1st Department of Medicine, Christian Albrechts University of Kiel, Germany. hschaef@1med.uni-kiel.de
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Schäfer
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Diebel
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Arlt
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Trauzold
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Schmidt
D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D001665:Binding Sites; D006528:Carcinoma, Hepatocellular; D002455:Cell Division; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis / Q000235:genetics; D017781:Genes, Immediate-Early; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D017874:Immediate-Early Proteins; D008113:Liver Neoplasms; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D009363:Neoplasm Proteins; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D006023:Glycoproteins; C099815:IER3 protein, human; D017874:Immediate-Early Proteins; D008565:Membrane Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D015500:Chloramphenicol O-Acetyltransferase