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 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.
Flatt
P M
PM
Department of Biochemistry, Center in Molecular Toxicology, and the Vanderbilt-Ingram Cancer Center, 652 Medical Research Building II, Vanderbilt University School of Medicine, 2220 Pierce Avenue, Nashville, TN 37232-6305, Nashville, USA.
Polyak
K
K
Tang
L J
LJ
Scatena
C D
CD
Westfall
M D
MD
Rubinstein
L A
LA
Yu
J
J
Kinzler
K W
KW
Vogelstein
B
B
Hill
D E
DE
Pietenpol
J A
JA
D017209:Apoptosis; D002453:Cell Cycle; D002455:Cell Division; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D004317:Doxorubicin / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011506:Proteins / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051736:Proto-Oncogene Proteins c-mdm2; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000502:physiology*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; C411296:TP53I3 protein, human; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2