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Symbol report for TP53I3

HGNC data for TP53I3

Approved symbol
TP53I3
Approved name

tumor protein p53 inducible protein 3

Locus type
gene with protein product
HGNC ID
HGNC:19373
Symbol status
Approved
Alias symbols
PIG3
Chromosomal location
2p23.3
Bos taurus
TP53I3 VGNC:36235 VGNC
Canis familiaris
TP53I3 VGNC:47724 VGNC
Equus caballus
TP53I3 VGNC:24422 VGNC
Felis catus
TP53I3 VGNC:66464 VGNC
Macaca mulatta
TP53I3 VGNC:79194 VGNC
Pan troglodytes
TP53I3 VGNC:10793 VGNC
Rattus norvegicus
Tp53i3 RGD:41235940
Sus scrofa
TP53I3 VGNC:94328 VGNC
Three-dimensional structure and enzymatic function of proapoptotic human p53-inducible quinone oxidoreductase PIG3.
Porté S et al. J Biol Chem 2009 Jun;284(25)17194-17205
Porté S, Valencia E, Yakovtseva EA, Borràs E, Shafqat N, Debreczeny JÉ, Pike ACW, Oppermann U, Farrés J, Fita I, Parés X.
J Biol Chem 2009 Jun;284(25)17194-17205
Abstract: Tumor suppressor p53 regulates the expression of p53-induced genes (PIG) that trigger apoptosis. PIG3 or TP53I3 is the only known member of the medium chain dehydrogenase/reductase superfamily induced by p53 and is used as a proapoptotic marker. Although the participation of PIG3 in the apoptotic pathway is proven, the protein and its mechanism of action were never characterized. We analyzed human PIG3 enzymatic function and found NADPH-dependent reductase activity with ortho-quinones, which is consistent with the classification of PIG3 in the quinone oxidoreductase family. However, the activity is much lower than that of zeta-crystallin, a better known quinone oxidoreductase. In addition, we report the crystallographic structure of PIG3, which allowed the identification of substrate- and cofactor-binding sites, with residues fully conserved from bacteria to human. Tyr-59 in zeta-crystallin (Tyr-51 in PIG3) was suggested to participate in the catalysis of quinone reduction. However, kinetics of Tyr/Phe and Tyr/Ala mutants of both enzymes demonstrated that the active site Tyr is not catalytic but may participate in substrate binding, consistent with a mechanism based on propinquity effects. It has been proposed that PIG3 contribution to apoptosis would be through oxidative stress generation. We found that in vitro activity and in vivo overexpression of PIG3 accumulate reactive oxygen species. Accordingly, an inactive PIG3 mutant (S151V) did not produce reactive oxygen species in cells, indicating that enzymatically active protein is necessary for this function. This supports that PIG3 action is through oxidative stress produced by its enzymatic activity and provides essential knowledge for eventual control of apoptosis.
A polymorphic microsatellite that mediates induction of PIG3 by p53.
Contente A et al. Nat Genet 2002 Mar;30(3)315-320
Contente A, Dittmer A, Koch MC, Roth J, Dobbelstein M.
Nat Genet 2002 Mar;30(3)315-320
Abstract: The gene PIG3 is induced by the tumor suppressor p53 but not by p53 mutants unable to induce apoptosis, suggesting its involvement in p53-mediated cell death. Here we show that p53 directly binds and activates the PIG3 promoter, but not through the previously described DNA element. Instead, p53 interacts with a pentanucleotide microsatellite sequence within the PIG3 promoter (TGYCC)n where Y=C or T. Despite its limited similarity to the p53-binding consensus, this sequence is necessary and sufficient for transcriptional activation of the PIG3 promoter by p53 and binds specifically to p53 in vitro and in vivo. In a population of 117 healthy donors from Germany, the microsatellite was found to be polymorphic, the number of pentanucleotide repeats being 10, 15, 16 or 17, and the frequency of alleles 5.1%, 62.0%, 21.4% and 11.5%, respectively. The number of repeats directly correlated with the extent of transcriptional activation by p53. This is the first time that a microsatellite has been shown to mediate the induction of a promoter through direct interaction with a transcription factor. Moreover, this sequence of PIG3 is the first p53-responsive element found to be polymorphic. Inheritance of this microsatellite may affect an individual's susceptibility to cancer.
p53-dependent expression of PIG3 during proliferation, genotoxic stress, and reversible growth arrest.
Flatt PM et al. Cancer Lett 2000 Aug;156(1)63-72
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 Aug;156(1)63-72
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.