| Description | 2 isoforms: TP53INP1alpha, 18kDa (164 amino acids) and TP53INP1beta, 27kDa (240 amino acids). Both isoforms contain a PEST domain (sequence rich in proline, glutamic acid, serine and threonine between amino acids 26 and 62 found in proteins with half-lives of less than 2 h). |
| Expression | In mouse: TP53INP1 is expressed in thymus, spleen and bone marrow. It is also expressed at low levels in heart, stomach, liver, intestine, testis, kidney and pancreas. TP53INP1 expression is highly induced during the acute phase of mouse experimental pancreatitis (caerulein induced).
In cells lines: TP53INP1 is transcriptionally induced in response to stress in a p53-dependent and independent manner. Examples: in mouse fibroblast, it is induced upon adriamycin, methylmethane sulfonate, ethanol, H2O2, UV exposure and heat shock treatment; in neuronal cells by copper treatment; in pancreatic cancer cell lines by gemcitabine; in pro-B cells by IL-3 deprivation or treatement with staurosporine, cisplatin, camptothecin, methotrexate and paclitaxel; in mouse embryonic fibroblast (MEF), human fibroblasts and MCF7 by gamma irradiation; in melanoma cells by UV mimetic compound (4NQ).
TP53INP1 expression is regulated by different transcriptional regulators: p53, E2F1, p73 (in p53-/- cells), myc (in neuroblastoma cell lines) and PLZF (in hematopoietic cell lines). |
| Localisation | Nuclear when over-expressed and in PML-bodies (Promyelocytic leukemia protein) upon PML-IV over-expression. |
| Function | TP53INP1 is a tumor suppressor gene induced with different stress conditions. TP53INP1 overexpression leads to cell cycle arrest (G1 phase) and p53-dependent or independent apoptosis. TP53INP1 interacts with p53 and two kinases (HIPK2, and PKCd). These kinases phosphorylate p53 on serine 46 modifying the p53 activity. TP53INP1 can modulate the p53 and p73 transcriptional activity to potentiate pro-apoptotic pathways. Colitis and colitis-associated cancer are exacerbated in mice deficient for TP53INP1. |
| Homology | TP53INP1 is conserved between species (from fly to human). In vertebrates, one paralog has been identified, TP53INP2 localized on chromosome 20q11.2. TP53INP2 is involved in autophagy. |
| Note | |
| | |
| Entity | Pancreatic Adenocarcinoma |
| Note | TP53INP1 is lost early during pancreatic cancer progression (from the neoplasia stages PanIN2). This downregulation seems to be important for tumour development. TP53INP1 expression is down regulated by the oncogenic micro-RNA miR-155 during pancreatic cancer progression. |
| Disease | Sporadic cancer, very aggressive, epigenetic disease with known mutations/deletions of p53, K-Ras, SMAD4, p16, BRCA2, EGFR and HER2. |
| Prognosis | Very bad, with only 20% of patients reaching two years of survival, and 3% after 5 years. |
| | |
| | |
| Entity | Breast cancer |
| Note | TP53INP1 expression is lost during breast cancer development. |
| Disease | Mainly in female (only 1% in male). Genetic disorders known: loss of HER2 and ER expression, mutations in p53 and BRCA1. |
| Prognosis | Mortality rate: 25%. |
| | |
| | |
| Entity | Gastric cancer |
| Note | TP53INP1 expression is lost during cancer development. The decreased expression of TP53INP1 protein may reflect the malignant grade of gastric cancer. |
| Disease | 10% are familial. Mutations in APC, p53, Bcl-2. |
| Prognosis | The 5-year survival after surgical resection is 30-50% for patients with stage II and 10-25% for patients with stage III. |
| | |
| | |
| Entity | Anaplastic carcinoma of the thyroid (ATC) |
| Note | TP53INP1 is overexpressed in anaplastic thyroid carcinoma. |
| Disease | ATC is less than 2% of total thyroid cancer but represents 40% of death by thyroid cancer. It is a very aggressive cancer with early dissemination. |
| Prognosis | 5-year survival rate is less than 10%. |
| | |
| Cell cycle regulation targets of MYCN identified by gene expression microarrays. |
| Bell E, Lunec J, Tweddle DA. |
| Cell Cycle. 2007 May 15;6(10):1249-56. Epub 2007 May 1. |
| PMID 17495526 |
| |
| Identification of apoptosis-related PLZF target genes. |
| Bernardo MV, Yelo E, Gimeno L, Campillo JA, Parrado A. |
| Biochem Biophys Res Commun. 2007 Jul 27;359(2):317-22. Epub 2007 May 24. |
| PMID 17537403 |
| |
| Tumor protein 53-induced nuclear protein 1 is a major mediator of p53 antioxidant function. |
| Cano CE, Gommeaux J, Pietri S, Culcasi M, Garcia S, Seux M, Barelier S, Vasseur S, Spoto RP, Pebusque MJ, Dusetti NJ, Iovanna JL, Carrier A. |
| Cancer Res. 2009 Jan 1;69(1):219-26. |
| PMID 19118006 |
| |
| Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155, and its restoration inhibits pancreatic tumor development. |
| Gironella M, Seux M, Xie MJ, Cano C, Tomasini R, Gommeaux J, Garcia S, Nowak J, Yeung ML, Jeang KT, Chaix A, Fazli L, Motoo Y, Wang Q, Rocchi P, Russo A, Gleave M, Dagorn JC, Iovanna JL, Carrier A, Pebusque MJ, Dusetti NJ. |
| Proc Natl Acad Sci U S A. 2007 Oct 9;104(41):16170-5. Epub 2007 Oct 2. |
| PMID 17911264 |
| |
| Colitis and colitis-associated cancer are exacerbated in mice deficient for tumor protein 53-induced nuclear protein 1. |
| Gommeaux J, Cano C, Garcia S, Gironella M, Pietri S, Culcasi M, Pebusque MJ, Malissen B, Dusetti N, Iovanna J, Carrier A. |
| Mol Cell Biol. 2007 Mar;27(6):2215-28. Epub 2007 Jan 22. |
| PMID 17242209 |
| |
| Novel link between E2F and p53: proapoptotic cofactors of p53 are transcriptionally upregulated by E2F. |
| Hershko T, Chaussepied M, Oren M, Ginsberg D. |
| Cell Death Differ. 2005 Apr;12(4):377-83. |
| PMID 15706352 |
| |
| High level of tumour protein p53-induced nuclear protein 1 (TP53INP1) expression in anaplastic carcinoma of the thyroid. |
| Ito Y, Motoo Y, Yoshida H, Iovanna JL, Nakamura Y, Kuma K, Miyauchi A. |
| Pathology. 2006 Dec;38(6):545-7. |
| PMID 17393983 |
| |
| Effect of gemcitabine on the expression of apoptosis-related genes in human pancreatic cancer cells. |
| Jiang PH, Motoo Y, Sawabu N, Minamoto T. |
| World J Gastroenterol. 2006 Mar 14;12(10):1597-602. |
| PMID 16570353 |
| |
| Microarray analysis of radiation response genes in primary human fibroblasts. |
| Kis E, Szatmari T, Keszei M, Farkas R, Esik O, Lumniczky K, Falus A, Safrany G. |
| Int J Radiat Oncol Biol Phys. 2006 Dec 1;66(5):1506-14. Epub 2006 Oct 25. |
| PMID 17069989 |
| |
| The TP53INP2 protein is required for autophagy in mammalian cells. |
| Nowak J, Archange C, Tardivel-Lacombe J, Pontarotti P, Pebusque MJ, Vaccaro MI, Velasco G, Dagorn JC, Iovanna JL. |
| Mol Biol Cell. 2009 Feb;20(3):870-81. Epub 2008 Dec 3. |
| PMID 19056683 |
| |
| TP53INP2 is the new guest at the table of self-eating. |
| Nowak J, Iovanna JL. |
| Autophagy. 2009 Apr;5(3):383-4. Epub 2009 Apr 23. |
| PMID 19145107 |
| |
| Assignment of tumor protein p53 induced nuclear protein 1 (TP53INP1) gene to human chromosome band 8q22 by in situ hybridization. |
| Nowak J, Tomasini R, Mattei MG, Azizi Samir LA, Dagorn JC, Dusetti N, Iovanna JL, Pebusque MJ. |
| Cytogenet Genome Res. 2002;97(1-2):140E. |
| PMID 12438758 |
| |
| p53DINP1, a p53-inducible gene, regulates p53-dependent apoptosis. |
| Okamura S, Arakawa H, Tanaka T, Nakanishi H, Ng CC, Taya Y, Monden M, Nakamura Y. |
| Mol Cell. 2001 Jul;8(1):85-94. |
| PMID 11511362 |
| |
| TP53INP1 is a novel p73 target gene that induces cell cycle arrest and cell death by modulating p73 transcriptional activity. |
| Tomasini R, Seux M, Nowak J, Bontemps C, Carrier A, Dagorn JC, Pebusque MJ, Iovanna JL, Dusetti NJ. |
| Oncogene. 2005 Dec 8;24(55):8093-104. |
| PMID 16044147 |
| |
| Expression profiling of p53-target genes in copper-mediated neuronal apoptosis. |
| Vanlandingham JW, Tassabehji NM, Somers RC, Levenson CW. |
| Neuromolecular Med. 2005;7(4):311-24. |
| PMID 16391388 |
| |
