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

Flatt PM, Polyak K, Tang LJ, Scatena CD, Westfall MD, Rubinstein LA, Yu J, Kinzler KW, Vogelstein B, Hill DE, Pietenpol JA
Cancer Lett. 2000 156 (1): 63-72

PMID: 10840161 · DOI:10.1016/s0304-3835(00)00441-9

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.

MeSH Terms (16)

Apoptosis Cell Cycle Cell Division Colonic Neoplasms Cyclin-Dependent Kinase Inhibitor p21 Cyclins Doxorubicin Gene Expression Regulation Humans Intracellular Signaling Peptides and Proteins Nuclear Proteins Proteins Proto-Oncogene Proteins Proto-Oncogene Proteins c-mdm2 Tumor Cells, Cultured Tumor Suppressor Protein p53

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