In this study we describe a novel putative p53-responsive gene, designated p22/PACAP response gene 1 (PRG1), recently identified as a proliferation-associated early-response gene in rats. By means of electrophoretic mobility shift assay and CAT-reporter gene assay, we could demonstrate that the p53 binding site residing in the promoter of p22/PRG1 is functional in vitro. Furthermore, in clone 6 cells expression of p22/PRG1 is induced in parallel to p21/Waf1 under conditions permitting mutant p53 to adopt wild-type configuration. An increase of p22/PRG1 transcription was also observed in gamma-irradiated rat splenocytes, which undergo p53-dependent apoptosis. Our findings demonstrate that p22/PRG1 fulfills all essential criteria as a p53 target gene and might be implicated in p53-dependent apoptosis.