TP53INP1 (tumor protein p53 inducible nuclear protein 1)

2009-04-01   Mylène Seux , Alice Carrier , Juan Iovanna , Nelson Dusetti 

INSERM U.624, Parc Scientifique de Luminy, Case 915, 13288 Marseille Cedex 9, France


Atlas Image


Atlas Image
Green boxes: exons, black lines: introns, alternative splicing for TP53INP1beta in black and TP53INP1alpha in red.


Gene is ~24 kb, with 5 exons.


Alternative splicing: 2 transcripts: TP53INP1alpha (exons 1, 2, 3, 4 and 5 with a stop codon in the fourth exon) and TP53INP1beta (exons 1, 2, 3 and 5 with a stop codon in the fifth exon).



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).


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).


Nuclear when over-expressed and in PML-bodies (Promyelocytic leukemia protein) upon PML-IV over-expression.


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.


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.



No mutation identified.

Implicated in

Entity name
Pancreatic Adenocarcinoma
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.
Sporadic cancer, very aggressive, epigenetic disease with known mutations/deletions of p53, K-Ras, SMAD4, p16, BRCA2, EGFR and HER2.
Very bad, with only 20% of patients reaching two years of survival, and 3% after 5 years.
Entity name
Breast cancer
TP53INP1 expression is lost during breast cancer development.
Mainly in female (only 1% in male). Genetic disorders known: loss of HER2 and ER expression, mutations in p53 and BRCA1.
Mortality rate: 25%.
Entity name
Gastric cancer
TP53INP1 expression is lost during cancer development. The decreased expression of TP53INP1 protein may reflect the malignant grade of gastric cancer.
10% are familial. Mutations in APC, p53, Bcl-2.
The 5-year survival after surgical resection is 30-50% for patients with stage II and 10-25% for patients with stage III.
Entity name
Anaplastic carcinoma of the thyroid (ATC)
TP53INP1 is overexpressed in anaplastic thyroid carcinoma.
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.
5-year survival rate is less than 10%.


Pubmed IDLast YearTitleAuthors
174955262007Cell cycle regulation targets of MYCN identified by gene expression microarrays.Bell E et al
175374032007Identification of apoptosis-related PLZF target genes.Bernardo MV et al
191180062009Tumor protein 53-induced nuclear protein 1 is a major mediator of p53 antioxidant function.Cano CE et al
179112642007Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155, and its restoration inhibits pancreatic tumor development.Gironella M et al
172422092007Colitis and colitis-associated cancer are exacerbated in mice deficient for tumor protein 53-induced nuclear protein 1.Gommeaux J et al
157063522005Novel link between E2F and p53: proapoptotic cofactors of p53 are transcriptionally upregulated by E2F.Hershko T et al
173939832006High level of tumour protein p53-induced nuclear protein 1 (TP53INP1) expression in anaplastic carcinoma of the thyroid.Ito Y et al
165703532006Effect of gemcitabine on the expression of apoptosis-related genes in human pancreatic cancer cells.Jiang PH et al
170699892006Microarray analysis of radiation response genes in primary human fibroblasts.Kis E et al
190566832009The TP53INP2 protein is required for autophagy in mammalian cells.Nowak J et al
191451072009TP53INP2 is the new guest at the table of self-eating.Nowak J et al
124387582002Assignment of tumor protein p53 induced nuclear protein 1 (TP53INP1) gene to human chromosome band 8q22 by in situ hybridization.Nowak J et al
115113622001p53DINP1, a p53-inducible gene, regulates p53-dependent apoptosis.Okamura S et al
160441472005TP53INP1 is a novel p73 target gene that induces cell cycle arrest and cell death by modulating p73 transcriptional activity.Tomasini R et al
163913882005Expression profiling of p53-target genes in copper-mediated neuronal apoptosis.Vanlandingham JW et al

Other Information

Locus ID:

NCBI: 94241
MIM: 606185
HGNC: 18022
Ensembl: ENSG00000164938


dbSNP: 94241
ClinVar: 94241
TCGA: ENSG00000164938


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
HTLV-I infectionKEGGko05166
HTLV-I infectionKEGGhsa05166
Gene ExpressionREACTOMER-HSA-74160
Generic Transcription PathwayREACTOMER-HSA-212436
Transcriptional Regulation by TP53REACTOMER-HSA-3700989
TP53 Regulates Transcription of Cell Death GenesREACTOMER-HSA-5633008
TP53 Regulates Transcription of Genes Involved in Cytochrome C ReleaseREACTOMER-HSA-6803204
Regulation of TP53 ActivityREACTOMER-HSA-5633007
Regulation of TP53 Activity through PhosphorylationREACTOMER-HSA-6804756

Protein levels (Protein atlas)

Not detected


Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA443319Alzheimer DiseaseDiseaseLiterature, MultilinkAnnotationassociated24922517


Pubmed IDYearTitleCitations
189741422008Roles for microRNAs, miR-93 and miR-130b, and tumor protein 53-induced nuclear protein 1 tumor suppressor in cell growth dysregulation by human T-cell lymphotrophic virus 1.75
208898532011Genetic risk reclassification for type 2 diabetes by age below or above 50 years using 40 type 2 diabetes risk single nucleotide polymorphisms.65
160441472005TP53INP1 is a novel p73 target gene that induces cell cycle arrest and cell death by modulating p73 transcriptional activity.54
128514042003TP53INP1s and homeodomain-interacting protein kinase-2 (HIPK2) are partners in regulating p53 activity.52
224219682012TP53INP1, a tumor suppressor, interacts with LC3 and ATG8-family proteins through the LC3-interacting region (LIR) and promotes autophagy-dependent cell death.49
241521842013MiR-155 promotes proliferation of human breast cancer MCF-7 cells through targeting tumor protein 53-induced nuclear protein 1.42
249225172014Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease.39
256338402015TGF-β1 acts through miR-155 to down-regulate TP53INP1 in promoting epithelial-mesenchymal transition and cancer stem cell phenotypes.39
233330582013miR-17-5p/20a are important markers for gastric cancer and murine double minute 2 participates in their functional regulation.35
120670652002P53-dependent expression of the stress-induced protein (SIP).30


Mylène Seux ; Alice Carrier ; Juan Iovanna ; Nelson Dusetti

TP53INP1 (tumor protein p53 inducible nuclear protein 1)

Atlas Genet Cytogenet Oncol Haematol. 2009-04-01

Online version: