Alternative titles; symbols
HGNC Approved Gene Symbol: TP53INP1
Cytogenetic location: 8q22.1 Genomic coordinates (GRCh38) : 8:94,925,972-94,949,378 (from NCBI)
Using differential display analysis with a cell line that carries a well-controlled expression system for wildtype p53 (191170), followed by screening a thymus cDNA library, Okamura et al. (2001) isolated cDNAs encoding a p53-inducible nuclear protein, P53DINP1. Alternative splicing generates 2 P53DINP1 transcripts, P53DINP1a and P53DINP1b, which encode 240- and 164-amino acid proteins, respectively. Northern blot analysis detected a 6-kb P53DINP1 transcript in all tissues tested, with relatively higher expression in pancreas, spleen, testis, and peripheral leukocyte.
Cell death induced by DNA double-strand breaks (DSBs), as well as ser46 phosphorylation of p53 and induction of P53AIP1 (605426), were blocked when Okamura et al. (2001) inhibited expression of P53DINP1 by means of an antisense oligonucleotide. Overexpression of P53DINP1 and DNA damage by DSBs synergistically enhanced ser46 phosphorylation of p53, induction of P53AIP1 expression, and apoptotic cell death. Furthermore, the protein complex interacting with P53DINP1 was found to phosphorylate ser46 of p53. These results suggested that P53DINP1 may regulate p53-dependent apoptosis through phosphorylation of p53 at ser46, serving as a cofactor for the putative p53-ser46 kinase.
Using immunohistochemical analysis, Gironella et al. (2007) showed that expression of TP53INP1 was dramatically reduced in pancreatic ductal adenocarcinomas compared with normal tissue, and that this decrease occurred early during pancreatic cancer development. TP53INP1 expression was repressed by the microRNA miR155 (MIRN155; 609337), which showed elevated expression in a majority of pancreatic carcinoma samples examined. Using reporter gene assays and anti-miR155 oligonucleotides, Gironella et al. (2007) demonstrated that miR155 targeted the 3-prime UTR of the TP53INP1 gene.
Using human pancreatic carcinoma cells and mouse fibroblasts, Seux et al. (2011) found that TP53INP1 inactivation increased cell migration in vivo and in vitro. TP53INP1 modulated cell-extracellular matrix adhesion by downregulating expression of SPARC (182120), a regulator cell-matrix interaction.
Okamura et al. (2001) determined that the P53DINP1 gene contains 4 exons and spans 15 kb.
By FISH, Okamura et al. (2001) mapped the P53DINP1 gene to 8q22.
Gironella, M., Seux, M., Xie, M.-J., Cano, C., Tomasini, R., Gommeaux, J., Garcia, S., Nowak, J., Yeung, M. L., Jeang, K.-T., Chaix, A., Fazli, L., and 10 others. Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155, and its restoration inhibits pancreatic tumor development. Proc. Nat. Acad. Sci. 104: 16170-16175, 2007. [PubMed: 17911264] [Full Text: https://doi.org/10.1073/pnas.0703942104]
Okamura, S., Arakawa, H., Tanaka, T., Nakanishi, H., Ng, C. C., Taya, Y., Monden, M., Nakamura, Y. p53DINP1, a p53-inducible gene, regulates p53-dependent apoptosis. Molec. Cell 8: 85-94, 2001. [PubMed: 11511362] [Full Text: https://doi.org/10.1016/s1097-2765(01)00284-2]
Seux, M., Peuget, S., Montero, M. P., Siret, C., Rigot, V., Clerc, P., Gigoux, V., Pellegrino, E., Pouyet, L., N'Guessan, P., Garcia, S., Dufresne, M., Iovanna, J. L., Carrier, A., Andre, F., Dusetti, N. J. TP53INP1 decreases pancreatic cancer cell migration by regulating SPARC expression. Oncogene 30: 3049-3061, 2011. [PubMed: 21339733] [Full Text: https://doi.org/10.1038/onc.2011.25]