p53-dependent expression of PIG3 during proliferation, genotoxic stress, and reversible growth arrest

The p53-inducible gene 3 (PIG3) was recently identified in a screen for gen es induced by p53 before the onset of apoptosis. PIG3 shares significant ho mology with oxidoreductases from several species. In this study, PTG3-speci fic antibodies were used to analyze cellular PIGS protein levels under cont rol and genotoxic stress conditions. PIG3 protein was localized to the cyto plasm and induced in primary, non-transformed, and transformed cell culture s after exposure to genotoxic agents. The induction of PIGS was p53-depende nt and occurred with delayed kinetics as compared with other p53 downstream targets, such as p21 and MDM2. Using a p53-inducible cell model system, in which p53-mediated growth arrest is reversible, we found that PIG3 levels were increased during p53-mediated growth arrest. Interestingly, elevated l evels of PIG3 were maintained in cells that resumed cycling in the absence of ectopic p53 expression, suggesting that PIG3 is a long-lived reporter, w hich may be useful for detecting transient activation of p53. (C) 2000 Else vier Science Ireland Ltd. All rights reserved.