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Cancer Lett ; 156(1): 63-72, 2000 Aug 01.
Article in English | MEDLINE | ID: mdl-10840161

ABSTRACT

The p53-inducible gene 3 (PIG3) was recently identified in a screen for genes induced by p53 before the onset of apoptosis. PIG3 shares significant homology with oxidoreductases from several species. In this study, PIG3-specific antibodies were used to analyze cellular PIG3 protein levels under control and genotoxic stress conditions. PIG3 protein was localized to the cytoplasm and induced in primary, non-transformed, and transformed cell cultures after exposure to genotoxic agents. The induction of PIG3 was p53-dependent 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 levels of PIG3 were maintained in cells that resumed cycling in the absence of ectopic p53 expression, suggesting that PIG3 is a long-lived reporter, which may be useful for detecting transient activation of p53.


Subject(s)
Nuclear Proteins , Proteins/physiology , Tumor Suppressor Protein p53/physiology , Apoptosis , Cell Cycle , Cell Division , Colonic Neoplasms/drug therapy , Colonic Neoplasms/pathology , Colonic Neoplasms/radiotherapy , Cyclin-Dependent Kinase Inhibitor p21 , Cyclins/genetics , Doxorubicin/pharmacology , Gene Expression Regulation , Humans , Intracellular Signaling Peptides and Proteins , Proto-Oncogene Proteins/physiology , Proto-Oncogene Proteins c-mdm2 , Tumor Cells, Cultured , Tumor Suppressor Protein p53/analysis
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