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Gene Review

TP53I3  -  tumor protein p53 inducible protein 3

Homo sapiens

Synonyms: PIG3, Quinone oxidoreductase PIG3, Tumor protein p53-inducible protein 3, p53-induced gene 3 protein
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Disease relevance of TP53I3

  • Here, we describe the transcriptional activity of the p53 mutant C277Y isolated from a Ewing's sarcoma with high constitutive pig3 expression [1].

High impact information on TP53I3

  • Here we show that p53 directly binds and activates the PIG3 promoter, but not through the previously described DNA element [2].
  • Instead, p53 interacts with a pentanucleotide microsatellite sequence within the PIG3 promoter (TGYCC)n where Y=C or T [2].
  • Moreover, this sequence of PIG3 is the first p53-responsive element found to be polymorphic [2].
  • One of the p53 target genes, p53-inducible gene 3 (PIG3), encodes a protein with significant homology to oxidoreductases, enzymes involved in cellular responses to oxidative stress and irradiation [3].
  • Depletion of BRCA1 in wild-type-p53-expressing cells abolished the induction of such repair genes as p53R2, while the expression of PIG3, an apoptosis-inducing gene, was still induced [4].

Biological context of TP53I3

  • The pentanucleotide microsatellite sequence present in exon 1 of the pig3 gene was found to be responsible for p53-C277Y-mediated activation [1].
  • The p53-inducible gene 3 (PIG3) is a transcriptional target of the tumor suppressor protein p53 and is thought to play a role in apoptosis [5].
  • PIG3AS results from alternative pre-mRNA splicing that skips exon 4 of the five exons included in the PIG3 transcript [5].
  • UV-dependent alternative splicing uncouples p53 activity and PIG3 gene function through rapid proteolytic degradation [5].
  • In unstressed cells and after most DNA damage conditions that induce transcription from the PIG3 gene, production of the PIG3 transcript dominates [5].

Anatomical context of TP53I3

  • Expression of endogenous pig3 and MDM2 genes was further enhanced on irradiation of this cell line [1].

Associations of TP53I3 with chemical compounds

  • The flavine-dependent oxidoreductase inhibitor diphenylene iodonium failed to inhibit generation of ROS in irradiated OCI/AML-2 cells, indicating that the mechanism is unlikely to involve the TP53-induced gene PIG3 [6].


  1. Constitutive and DNA damage inducible activation of pig3 and MDM2 genes by tumor-derived p53 mutant C277Y. Pospísilová, S., Siligan, C., Ban, J., Jug, G., Kovar, H. Mol. Cancer Res. (2004) [Pubmed]
  2. A polymorphic microsatellite that mediates induction of PIG3 by p53. Contente, A., Dittmer, A., Koch, M.C., Roth, J., Dobbelstein, M. Nat. Genet. (2002) [Pubmed]
  3. Regulation of p53 stability and p53-dependent apoptosis by NADH quinone oxidoreductase 1. Asher, G., Lotem, J., Cohen, B., Sachs, L., Shaul, Y. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  4. BRCA1 directs a selective p53-dependent transcriptional response towards growth arrest and DNA repair targets. MacLachlan, T.K., Takimoto, R., El-Deiry, W.S. Mol. Cell. Biol. (2002) [Pubmed]
  5. UV-dependent alternative splicing uncouples p53 activity and PIG3 gene function through rapid proteolytic degradation. Nicholls, C.D., Shields, M.A., Lee, P.W., Robbins, S.M., Beattie, T.L. J. Biol. Chem. (2004) [Pubmed]
  6. An oxidative stress-mediated death pathway in irradiated human leukemia cells mapped using multilaser flow cytometry. Sheng-Tanner, X., Bump, E.A., Hedley, D.W. Radiat. Res. (1998) [Pubmed]
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