TRIAP1 (TP53 regulated inhibitor of apoptosis 1)

2011-02-01   Veruska Alves , Roberta Felix , Andre Vettore , Gisele Colleoni 

Universidade Federal de Sao Paulo - UNIFESP, Laboratory of Cancer Molecular Biology, Sao Paulo, Brazil

Identity

HGNC
LOCATION
12q24.31
LOCUSID
ALIAS
HSPC132,MDM35,P53CSV,WF-1
FUSION GENES

DNA/RNA

Atlas Image
Figure 1.

Description

2452 bases, starts at 119366147 and ends at 119368598 bp from promoter with minus strand orientation.

Transcription

This gene contains 2 introns which transcription gives 3 different mRNAs, 2 alternatively spliced variants and 1 unspliced form that encodes good proteins (see figure 1).

Proteins

Note

The P53CSV protein is involved in programmed cell death. It contains a p53-binding site and it is induced when cells are at low genotoxic stress. It is probably involved in cell survival by interaction between Apaf-1 (apoptosis protease activating factor 1) and heat shock protein 70 (Hsp70) with subsequent inhibition of caspase-9 activation.

Description

This protein contains 76 amino acids and has 8786 (Da) of weight.
Atlas Image
Figure 2.

Localisation

The protein is localized in cytoplasm and perinuclear region.

Function

P53CSV is a novel p53-target gene. This gene can modulate apoptotic pathways by interaction with heat shock protein 70 (HSP70), preventing the induction of apoptosis. When cells are submitted to low levels of genotoxic stress, it is an important player in P53-mediated cell survivor pathway (Park and Nakamura, 2005; Felix et al., 2009).
P53CSV can inhibit apoptosis through interaction with APAF1 and HSP70 complex.
Atlas Image
Figure 3. Hypothetical illustration about TRIAP1 (P53CSV) involvement in the p53-dependent cell survival pathway. The TRIAP1 mediates cell survival at low level of genotoxic stress by inhibiting activation of the complex APAF-1/caspase-9/cytochrome C preventing the apoptosis induction.
Atlas Image
Figure 4. Hypothetical P53CSV mechanism of action in interaction with heat shock protein 70 in normal and tumor cells (Felix et al., 2009).

Mutations

Note

There are two identified alterations until now. One of them is located at position 270 of mRNA and the allele G (guanine) is switched to the allele C (cytosine) at position 77 of the amino acid sequence protein. The other one is a synonymous alteration localized at position 160 of mRNA involving the protein residue Leucine. The allele C (cytosine) is switched to the allele T (thymine) at position 40 of the amino acid sequence protein (NCBI).

Implicated in

Entity name
Note
Felix et al. (2009), described that P53CSV gene was upregulated in multiple myeloma SAGE (serial analysis of gene expression) library when compared to normal/reactive plasma cells. They suggested that the interaction between P53CSV/Hsp70 should be evaluated as a potential target for multiple myeloma patients. Real time quantitative PCR analyses confirmed upregulation of P53CSV in 90% of multiple myeloma plasma samples cells.
Entity name
Inflammatory stress
Note
Staib et al. (2005) reported P53CSV expression in colon carcinoma cells in the course of inflammatory responses associated with four microenvironmental components: nitric oxide, hydrogen peroxide, DNA replication arrest, and hypoxia.
Entity name
Solid cancers
Note
Yu Kun et al. (2008), using a genome-wide computational strategy identified genes exhibiting precise transcriptional control in solid tumors and evaluated if they linked to multiple cancer-related pathways such as metastatic and invasive potential. siRNA knockdown of five genes supports the existence of precisely controlled genes in solid tumors, including P53CSV.

Bibliography

Pubmed IDLast YearTitleAuthors
191714222009SAGE analysis highlights the importance of p53csv, ddx5, mapkapk2 and ranbp2 to multiple myeloma tumorigenesis.Felix RS et al
157350032005p53CSV, a novel p53-inducible gene involved in the p53-dependent cell-survival pathway.Park WR et al
162880132005The p53 tumor suppressor network is a key responder to microenvironmental components of chronic inflammatory stress.Staib F et al
186361072008A precisely regulated gene expression cassette potently modulates metastasis and survival in multiple solid cancers.Yu K et al

Other Information

Locus ID:

NCBI: 51499
MIM: 614943
HGNC: 26937
Ensembl: ENSG00000170855

Variants:

dbSNP: 51499
ClinVar: 51499
TCGA: ENSG00000170855
COSMIC: TRIAP1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000170855ENST00000546954O43715

Expression (GTEx)

0
10
20
30
40
50
60
70
80

Pathways

PathwaySourceExternal ID
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

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
239317592013TRIAP1/PRELI complexes prevent apoptosis by mediating intramitochondrial transport of phosphatidic acid.53
236846072013A genetic screen identifies TCF3/E2A and TRIAP1 as pathway-specific regulators of the cellular response to p53 activation.28
157350032005p53CSV, a novel p53-inducible gene involved in the p53-dependent cell-survival pathway.22
157350032005p53CSV, a novel p53-inducible gene involved in the p53-dependent cell-survival pathway.22
260716022015Structural insight into the TRIAP1/PRELI-like domain family of mitochondrial phospholipid transfer complexes.21
274283742016Overexpression of Mitochondria Mediator Gene TRIAP1 by miR-320b Loss Is Associated with Progression in Nasopharyngeal Carcinoma.19
208776242010Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.17
157356652005topors, a p53 and topoisomerase I-binding RING finger protein, is a coactivator of p53 in growth suppression induced by DNA damage.15
191714222009SAGE analysis highlights the importance of p53csv, ddx5, mapkapk2 and ranbp2 to multiple myeloma tumorigenesis.15
270323842016TP53 Regulated Inhibitor of Apoptosis 1 (TRIAP1) stable silencing increases late apoptosis by upregulation of caspase 9 and APAF1 in RPMI8226 multiple myeloma cell line.8

Citation

Veruska Alves ; Roberta Felix ; Andre Vettore ; Gisele Colleoni

TRIAP1 (TP53 regulated inhibitor of apoptosis 1)

Atlas Genet Cytogenet Oncol Haematol. 2011-02-01

Online version: http://atlasgeneticsoncology.org/gene/44577/triap1