TP53INP1 (tumor protein p53 inducible nuclear protein 1)

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

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

Identity

HGNC

TP53INP1

LOCATION

8q22.1

IMAGE

LOCUSID

94241

ALIAS

SIP,TP53DINP1,TP53INP1A,TP53INP1B,Teap,p53DINP1

FUSION GENES

Show Gene Fusions

DNA/RNA

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

Description

Gene is ~24 kb, with 5 exons.

Transcription

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).

Proteins

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.

Mutations

Note

No mutation identified.

Implicated in

Entity name

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 name

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 name

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 name

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%.

Article Bibliography

Pubmed ID	Last Year	Title	Authors
17495526	2007	Cell cycle regulation targets of MYCN identified by gene expression microarrays.	Bell E et al
17537403	2007	Identification of apoptosis-related PLZF target genes.	Bernardo MV et al
19118006	2009	Tumor protein 53-induced nuclear protein 1 is a major mediator of p53 antioxidant function.	Cano CE et al
17911264	2007	Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155, and its restoration inhibits pancreatic tumor development.	Gironella M et al
17242209	2007	Colitis and colitis-associated cancer are exacerbated in mice deficient for tumor protein 53-induced nuclear protein 1.	Gommeaux J et al
15706352	2005	Novel link between E2F and p53: proapoptotic cofactors of p53 are transcriptionally upregulated by E2F.	Hershko T et al
17393983	2006	High level of tumour protein p53-induced nuclear protein 1 (TP53INP1) expression in anaplastic carcinoma of the thyroid.	Ito Y et al
16570353	2006	Effect of gemcitabine on the expression of apoptosis-related genes in human pancreatic cancer cells.	Jiang PH et al
17069989	2006	Microarray analysis of radiation response genes in primary human fibroblasts.	Kis E et al
19056683	2009	The TP53INP2 protein is required for autophagy in mammalian cells.	Nowak J et al
19145107	2009	TP53INP2 is the new guest at the table of self-eating.	Nowak J et al
12438758	2002	Assignment of tumor protein p53 induced nuclear protein 1 (TP53INP1) gene to human chromosome band 8q22 by in situ hybridization.	Nowak J et al
11511362	2001	p53DINP1, a p53-inducible gene, regulates p53-dependent apoptosis.	Okamura S et al
16044147	2005	TP53INP1 is a novel p73 target gene that induces cell cycle arrest and cell death by modulating p73 transcriptional activity.	Tomasini R et al
16391388	2005	Expression 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

Variants:

dbSNP: 94241
ClinVar: 94241
TCGA: ENSG00000164938
COSMIC: TP53INP1

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000164938	ENST00000342697	Q96A56
ENSG00000164938	ENST00000342697	A0A024R9C8
ENSG00000164938	ENST00000448464	Q96A56

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
HTLV-I infection	KEGG	ko05166
HTLV-I infection	KEGG	hsa05166
Gene Expression	REACTOME	R-HSA-74160
Generic Transcription Pathway	REACTOME	R-HSA-212436
Transcriptional Regulation by TP53	REACTOME	R-HSA-3700989
TP53 Regulates Transcription of Cell Death Genes	REACTOME	R-HSA-5633008
TP53 Regulates Transcription of Genes Involved in Cytochrome C Release	REACTOME	R-HSA-6803204
Regulation of TP53 Activity	REACTOME	R-HSA-5633007
Regulation of TP53 Activity through Phosphorylation	REACTOME	R-HSA-6804756

Protein levels (Protein atlas)

Not detected

Low

Medium

High

PharmGKB

Entity ID	Name	Type	Evidence	Association	PK	PD	PMIDs
PA443319	Alzheimer Disease	Disease	Literature, MultilinkAnnotation	associated			24922517

References

Pubmed ID	Year	Title	Citations
38267567	2024	An approach for an enhanced anticancer activity of ferulic acid-loaded polymeric micelles via MicroRNA-221 mediated activation of TP53INP1 in caco-2 cell line.	0
38267567	2024	An approach for an enhanced anticancer activity of ferulic acid-loaded polymeric micelles via MicroRNA-221 mediated activation of TP53INP1 in caco-2 cell line.	0
35164998	2022	MiR-155 inhibits TP53INP1 expression leading to enhanced glycolysis of psoriatic mesenchymal stem cells.	4
35802258	2022	LncRNA n339260 functions in hepatocellular carcinoma progression via regulation of miRNA30e-5p/TP53INP1 expression.	2
35876212	2022	miR-8485 alleviates the injury of cardiomyocytes through TP53INP1.	2
35164998	2022	MiR-155 inhibits TP53INP1 expression leading to enhanced glycolysis of psoriatic mesenchymal stem cells.	4
35802258	2022	LncRNA n339260 functions in hepatocellular carcinoma progression via regulation of miRNA30e-5p/TP53INP1 expression.	2
35876212	2022	miR-8485 alleviates the injury of cardiomyocytes through TP53INP1.	2
33966044	2021	TP53INP1 exerts neuroprotection under ageing and Parkinson's disease-related stress condition.	4
34152408	2021	FOXO1 mediates hypoxia-induced G0/G1 arrest in ovarian somatic granulosa cells by activating the TP53INP1-p53-CDKN1A pathway.	7
34718338	2021	MicroRNA-106a regulates autophagy-related cell death and EMT by targeting TP53INP1 in lung cancer with bone metastasis.	16
33966044	2021	TP53INP1 exerts neuroprotection under ageing and Parkinson's disease-related stress condition.	4
34152408	2021	FOXO1 mediates hypoxia-induced G0/G1 arrest in ovarian somatic granulosa cells by activating the TP53INP1-p53-CDKN1A pathway.	7
34718338	2021	MicroRNA-106a regulates autophagy-related cell death and EMT by targeting TP53INP1 in lung cancer with bone metastasis.	16
31669646	2020	TNF-α/miR-155 axis induces the transformation of osteosarcoma cancer stem cells independent of TP53INP1.	17

Citation

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: http://atlasgeneticsoncology.org/gene/42672/gene-fusions/css/favicon/manifest.json