PA26, a novel target of the p53 tumor suppressor and member of the GADD family of DNA damage and growth arrest inducible genes

Exposure of mammalian cells to hypoxia, radiation and certain chemotherapeu tic agents promotes cell cycle arrest and/or apoptosis. Activation of p53 r esponsive genes is believed to play an important role in mediating such res ponses. In this study we identified a novel gene, PA26, which maps to chrom osome 6q21 and encodes at least three transcript isoforms, of which two are differentially induced by genotoxic stress (UV, gamma-irradiation and cyto toxic drugs) in a p53-dependent manner. A functional p53-responsive element was identified in the second intron of the PA26 gene, in consistence with a mechanism of transcriptional induction of the PA26 gene by p53. No clues to its functions were revealed by sequence analysis, although pronounced ne gative regulation by serum factors argues fbr a potential role of PA26 in g rowth regulation. Immunological analysis suggests that PA26 protein(s) is l ocalized to the cell nucleus. Our results suggest that the PA26 gene is a n ovel p53 target gene with properties common to the GADD family of growth ar rest and DNA damage-inducible stress-response genes, and, thus, a potential novel regulator of cellular growth.