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TP53INP1 (tumor protein p53 inducible nuclear protein 1)

Written2009-04Mylène Seux, Alice Carrier, Juan Iovanna, Nelson Dusetti
INSERM U.624, Parc Scientifique de Luminy, Case 915, 13288 Marseille Cedex 9, France

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)DKFZp434M1317
FLJ22139
P53DINP1
SIP
TP53INP1A
TP53INP1B
Teap
Other aliasTEAP
p53DINP1
TP53DINP1
HGNC (Hugo) TP53INP1
LocusID (NCBI) 94241
Atlas_Id 42672
Location 8q22.1  [Link to chromosome band 8q22]
Location_base_pair Starts at 94925972 and ends at 94949387 bp from pter ( according to hg19-Feb_2009)  [Mapping TP53INP1.png]
 
Fusion genes
(updated 2016)
BAG4 (8p11.23) / TP53INP1 (8q22.1)CFH (1q31.3) / TP53INP1 (8q22.1)IRX3 (16q12.2) / TP53INP1 (8q22.1)
PLEKHF2 (8q22.1) / TP53INP1 (8q22.1)

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).

Protein

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

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%.
  

Bibliography

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
 

Citation

This paper should be referenced as such :
Seux, M ; Carrier, A ; Iovanna, J ; Dusetti, N
TP53INP1 (tumor protein p53 inducible nuclear protein 1)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(3):311-313.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/TP53INP1ID42672ch8q22.html


External links

Nomenclature
HGNC (Hugo)TP53INP1   18022
Cards
AtlasTP53INP1ID42672ch8q22
Entrez_Gene (NCBI)TP53INP1  94241  tumor protein p53 inducible nuclear protein 1
AliasesSIP; TP53DINP1; TP53INP1A; TP53INP1B; 
Teap; p53DINP1
GeneCards (Weizmann)TP53INP1
Ensembl hg19 (Hinxton)ENSG00000164938 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000164938 [Gene_View]  chr8:94925972-94949387 [Contig_View]  TP53INP1 [Vega]
ICGC DataPortalENSG00000164938
TCGA cBioPortalTP53INP1
AceView (NCBI)TP53INP1
Genatlas (Paris)TP53INP1
WikiGenes94241
SOURCE (Princeton)TP53INP1
Genetics Home Reference (NIH)TP53INP1
Genomic and cartography
GoldenPath hg38 (UCSC)TP53INP1  -     chr8:94925972-94949387 -  8q22.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)TP53INP1  -     8q22.1   [Description]    (hg19-Feb_2009)
EnsemblTP53INP1 - 8q22.1 [CytoView hg19]  TP53INP1 - 8q22.1 [CytoView hg38]
Mapping of homologs : NCBITP53INP1 [Mapview hg19]  TP53INP1 [Mapview hg38]
OMIM606185   
Gene and transcription
Genbank (Entrez)AB017926 AB017927 AF409114 AF409115 AK025792
RefSeq transcript (Entrez)NM_001135733 NM_033285
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)TP53INP1
Cluster EST : UnigeneHs.492261 [ NCBI ]
CGAP (NCI)Hs.492261
Alternative Splicing GalleryENSG00000164938
Gene ExpressionTP53INP1 [ NCBI-GEO ]   TP53INP1 [ EBI - ARRAY_EXPRESS ]   TP53INP1 [ SEEK ]   TP53INP1 [ MEM ]
Gene Expression Viewer (FireBrowse)TP53INP1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)94241
GTEX Portal (Tissue expression)TP53INP1
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ96A56   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ96A56  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ96A56
Splice isoforms : SwissVarQ96A56
PhosPhoSitePlusQ96A56
Domains : Interpro (EBI)TP53INP    TP53INP1   
Domain families : Pfam (Sanger)DOR (PF14839)   
Domain families : Pfam (NCBI)pfam14839   
Conserved Domain (NCBI)TP53INP1
DMDM Disease mutations94241
Blocks (Seattle)TP53INP1
SuperfamilyQ96A56
Human Protein AtlasENSG00000164938
Peptide AtlasQ96A56
HPRD09367
IPIIPI00059265   IPI00554684   IPI00952643   
Protein Interaction databases
DIP (DOE-UCLA)Q96A56
IntAct (EBI)Q96A56
FunCoupENSG00000164938
BioGRIDTP53INP1
STRING (EMBL)TP53INP1
ZODIACTP53INP1
Ontologies - Pathways
QuickGOQ96A56
Ontology : AmiGOautophagosome assembly  protein binding  nucleus  nucleoplasm  autophagosome  cytosol  transcription, DNA-templated  apoptotic process  response to stress  cell cycle arrest  negative regulation of cell proliferation  response to heat  positive regulation of autophagy  negative regulation of gene expression  antioxidant activity  PML body  negative regulation of cell migration  cytoplasmic vesicle  cellular response to UV  regulation of apoptotic process  positive regulation of transcription, DNA-templated  autophagic cell death  negative regulation of fibroblast proliferation  cellular response to ethanol  cellular response to hydroperoxide  cellular response to methyl methanesulfonate  cellular oxidant detoxification  regulation of signal transduction by p53 class mediator  negative regulation of myofibroblast differentiation  positive regulation of apoptotic signaling pathway  
Ontology : EGO-EBIautophagosome assembly  protein binding  nucleus  nucleoplasm  autophagosome  cytosol  transcription, DNA-templated  apoptotic process  response to stress  cell cycle arrest  negative regulation of cell proliferation  response to heat  positive regulation of autophagy  negative regulation of gene expression  antioxidant activity  PML body  negative regulation of cell migration  cytoplasmic vesicle  cellular response to UV  regulation of apoptotic process  positive regulation of transcription, DNA-templated  autophagic cell death  negative regulation of fibroblast proliferation  cellular response to ethanol  cellular response to hydroperoxide  cellular response to methyl methanesulfonate  cellular oxidant detoxification  regulation of signal transduction by p53 class mediator  negative regulation of myofibroblast differentiation  positive regulation of apoptotic signaling pathway  
Pathways : KEGGHTLV-I infection   
REACTOMEQ96A56 [protein]
REACTOME PathwaysR-HSA-6804756 [pathway]   
NDEx NetworkTP53INP1
Atlas of Cancer Signalling NetworkTP53INP1
Wikipedia pathwaysTP53INP1
Orthology - Evolution
OrthoDB94241
GeneTree (enSembl)ENSG00000164938
Phylogenetic Trees/Animal Genes : TreeFamTP53INP1
HOVERGENQ96A56
HOGENOMQ96A56
Homologs : HomoloGeneTP53INP1
Homology/Alignments : Family Browser (UCSC)TP53INP1
Gene fusions - Rearrangements
Fusion : MitelmanBAG4/TP53INP1 [8p11.23/8q22.1]  [t(8;8)(p11;q22)]  
Fusion : MitelmanPLEKHF2/TP53INP1 [8q22.1/8q22.1]  [t(8;8)(q22;q22)]  
Fusion: TCGABAG4 8p11.23 TP53INP1 8q22.1 BRCA
Fusion: TCGAPLEKHF2 8q22.1 TP53INP1 8q22.1 LUAD
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerTP53INP1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)TP53INP1
dbVarTP53INP1
ClinVarTP53INP1
1000_GenomesTP53INP1 
Exome Variant ServerTP53INP1
ExAC (Exome Aggregation Consortium)TP53INP1 (select the gene name)
Genetic variants : HAPMAP94241
Genomic Variants (DGV)TP53INP1 [DGVbeta]
DECIPHERTP53INP1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisTP53INP1 
Mutations
ICGC Data PortalTP53INP1 
TCGA Data PortalTP53INP1 
Broad Tumor PortalTP53INP1
OASIS PortalTP53INP1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICTP53INP1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDTP53INP1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch TP53INP1
DgiDB (Drug Gene Interaction Database)TP53INP1
DoCM (Curated mutations)TP53INP1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)TP53INP1 (select a term)
intoGenTP53INP1
NCG5 (London)TP53INP1
Cancer3DTP53INP1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM606185   
Orphanet
MedgenTP53INP1
Genetic Testing Registry TP53INP1
NextProtQ96A56 [Medical]
TSGene94241
GENETestsTP53INP1
Target ValidationTP53INP1
Huge Navigator TP53INP1 [HugePedia]
snp3D : Map Gene to Disease94241
BioCentury BCIQTP53INP1
ClinGenTP53INP1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD94241
Chemical/Pharm GKB GenePA38278
Clinical trialTP53INP1
Miscellaneous
canSAR (ICR)TP53INP1 (select the gene name)
Other databaseUMD-TP53 (tumor protein p53). Curator: T. Soussi
Probes
Litterature
PubMed42 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineTP53INP1
EVEXTP53INP1
GoPubMedTP53INP1
iHOPTP53INP1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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