THE PROMOTER OF HUMAN P22 PACAP RESPONSE GENE 1 (PRG1) CONTAINS FUNCTIONAL BINDING-SITES FOR THE P53 TUMOR-SUPPRESSOR AND FOR NF-KAPPA-B/

We describe functional binding sites for the tumor suppressor p53 and for NF kappa B residing in the promoter of the novel human early respo nse gene p22/PRG1 (IEX-1/DLF-2). Gel shift and supershift assays demon strate binding of p53 and NF kappa B to their corresponding sites in v itro. CAT-reporter gene assays show transactivation of the human p22/P RG1 promoter by p53 in Hep3B cells stably transfected with a temperatu re-sensitive mutant p53, but not in p53-deficient Hep3B cells. TNF alp ha induced NF kappa B dependent transactivation was shown in HepG2 cel ls or in 818-4 pancreatic cancer cells. These data imply that human p2 2/PRG1 is a target gene for p53 and NF kappa B invoiced in growth regu lation and stress response. (C) 1998 Federation of European Biochemica l Societies.