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Tbio RelA-associated inhibitor

Regulator that plays a central role in regulation of apoptosis and transcription via its interaction with NF-kappa-B and p53/TP53 proteins. Blocks transcription of HIV-1 virus by inhibiting the action of both NF-kappa-B and SP1. Also inhibits p53/TP53 function, possibly by preventing the association between p53/TP53 and ASPP1 or ASPP2, and therefore suppressing the subsequent activation of apoptosis.

IASPP is one of the most evolutionarily conserved inhibitors of p53 (TP53; MIM 191170), whereas ASPP1 (MIM 606455) and ASPP2 (MIM 602143) are activators of p53.[supplied by OMIM, Mar 2008]

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Property Summary

NCBI Gene PubMed Count 83
PubMed Score 55.12
PubTator Score 67.39

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (3)

Disease Target Count
Leukemia 88
Disease Target Count Z-score Confidence
Cancer 2346 3.52 1.8

Expression

  Differential Expression (11)

Disease log2 FC p
malignant mesothelioma 2.500 2.0e-08
esophageal adenocarcinoma -1.500 3.0e-02
cutaneous lupus erythematosus -1.400 1.4e-02
pancreatic ductal adenocarcinoma liver m... 1.216 1.2e-02
colon cancer 1.100 2.9e-03
active ulcerative colitis 1.028 1.2e-02
interstitial cystitis -1.900 8.8e-05
posterior fossa group A ependymoma 1.200 4.4e-06
aldosterone-producing adenoma -1.040 9.0e-03
spina bifida -2.020 3.3e-02
pituitary cancer -1.100 5.7e-07

Synonym

Accession Q8WUF5 Q2PNZ9 Q5DU71 Q5I1X4 Q6P1R7 Q6PKF8 Q9Y290
Symbols RAI
RAI4
IASPP
NKIP1

Gene

PPP1R13L

PDB

2VGE  

  Ortholog (1)

Species Source Disease
Chimp OMA EggNOG

 UniProt Keyword (15)

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 GO Function (4)

 GO Component (6)

 GO Process (13)

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 Compartment GO Term (28)

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 MGI Phenotype (10)

 HCA RNA Cell Line (56)

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Pathway (9)

Protein-protein Interaction (1)

TP63  

Gene RIF (69)

PMID Text
27075368 one novel region within PPP1R13L is hypomethylated in all transient neonatal diabetes type 1 patients included in this study
26787707 inhibitor of apoptosis-stimulating protein of p53 (iASPP) was identified to be a direct target of miR-140 in pancreatic duct adenocarcinoma specimens and cell lines
26646590 we show that iASPP is a novel substrate of caspases in response to apoptotic stimuli
26109723 One of the proteins identified, iASPP, showed reduced levels in the presence of GSK-3. Further, blocking iASPP activity increased cell death, particularly in p53 wild-type BC3 PEL cells.
25917613 results suggest that NFKB1 common variants and smoking duration and smoking duration-PPP1R13L rs1970764 interaction could be concerned with the lung cancer development in a Chinese population
25691752 These data demonstrate that by interacting with desmoplakin and desmin, iASPP is an important regulator of desmosomal function both in vitro and in vivo.
25675294 destabilization of p300/CBP by downregulation of iASPP expression levels appears to represent a molecular mechanism that contributes to chemoresistance in melanoma cells.
25341046 iASPP expression may act as a predictive marker of prostate cancer progression.
25149434 The present study showed that iASPP is overexpressed in oral cavity squamous cell carcinomas (OSCC)tissues and increased cytoplasmic iASPP is correlated with recurrence and poor survival outcomes in OSCC patients
24997996 data highlight the importance of 14-3-3 proteins in antiviral responses and identify RelA-associated inhibitor and sirtuin 1 as novel regulators of antiviral innate immune responses.
24966937 MIRN124 binds to the 3'UTR of iASPP and suppressing mRNA expression and the proliferation of prostate tumor cells.
24777476 Authors have identified a novel mechanism modulating autophagy in keratinocytes that relies upon iASPP expression specifically reducing the interaction of Atg5-Atg12 with Atg16L1.
24668753 Hematopoietic cells can be protected against apoptosis by iASPP.
24604828 rs6966 (3' UTR of PPP1R13L, chr 19q13.32, P = 4.55 x 10(-9)) and rs414580 (intron 2 of MSR1, chr 8p22, P = 6.09 x 10(-8)) were significantly associated with ALL.
24405603 overexpression of iASPP and the low expression of caspase-9 in esophageal cancer are closely correlated with tumor invasion and metastasis
24140460 Haplotype PPP1R13L rs4803817 polymorphism is associated with lung cancer risk.
23691514 the miR-124/iASPP axis can regulate the proliferation of colorectal cancer cells.
23624869 Downregulation of miR-124 promotes the growth and invasiveness of glioblastoma cells involving upregulation of PPP1R13L.
23624123 PPP1R13L and CD3EAP variants may be associated with lung cancer risk in nonsmoking Chinese women.
23528480 higher rate Helicobacter pylori infection, an increased expression of inhibitor of apoptosis stimulating protein of p53 (iASPP), and decreased expression of apoptosis-stimulating of p53 protein 2(ASPP2) was present in gastric cancer
23420450 This study thus demonstrates that iASPP is highly elevated in human cervical cancer, and that overexpression of nuclear iASPP is correlated with poor prognosis and chemoresistance/radioresistance
23180017 The PPP1R13L rs1970764 variant is a possible prognostic marker for patients with rectal cancer.
23088536 When the Px(T)PxR motif is deleted or mutated via insertion of a phosphorylation site mimic (T311D), PP-1c fails to bind to all three ASPP proteins, ASPP1, ASPP2 and iASPP.
22815155 results suggest iASPP may contribute to the malignant progression of head and neck squamous cell carcinoma
22766503 These findings showed that iAPSS/iASPPsv reduced the growth inhibition and apoptosis induced by Dex or VP-16, with DNA damage accumulating which might promote the pathogenesis and/or progression of cancer.
22552744 Downregulation of iASPP by siRNA stimulated apoptosis through p53 in two non-small cell lung cancer cell lines
22538442 iASPP inhibited apoptosis independently of p53 in tumor cells, mainly by inhibiting the transcriptional activity of p63/p73 on the promoters of proapoptotic genes
22351191 Highly significant differential distributions of haplotypes defined by both nine haplotype-tagging SNPs covering ERCC2 and PPP1R13L and fourteen haplotype-tagging SNPs covering ERCC2, PPP1R13L, and ERCC1 were found.
22335888 variant alleles of PPP1R13L rs1970764 and CD3EAP rs967591 may contribute to risk factors of lung cancer.
21998301 Study identifies iASPP as a new binding partner of PP1, interacting through a noncanonical PP1 binding motif.
21926165 Data show an association of iASPP overexpression with gene amplification in ovarian cancer and suggest a role of iASPP in poor patient outcome and chemoresistance, through blocking mitotic catastrophe.
21897369 These data showed iASPP to be a key regulator of epithelial homeostasis in skin.
21625267 iASPP is essential for prostate cancer cellular proliferation and survival and may be a potential target for the gene therapy for prostate cancer
21391736 results showed that iASPP mRNA and protein levels were significantly down-regulated in both cells infected with the siRNA against iASPP
21192816 iASPP regulates the proliferation and motility of lung cancer cells. This effect is intimately associated with the p53 pathway.
21184255 Role of iASPP in cell cycle progression of glioblastoma cells.
21046104 Observational study of gene-disease association, gene-gene interaction, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20840860 Data provide evidence that endogenous PPP1R13L acts as a negative regulator of p53 function, presumably by direct binding.
20600029 iASPP is up-regulated in hepatocellular carcinoma; it is a direct transcription target of NF-kappaB
20422457 Single-nucleotide polymorphisms in PPP1R13L gene is associated with early-stage non-small-cell lung cancer.
20354815 results suggest that polymorphism Asn118Asn in ERCC1, A67T in iASPP and Asn148Glu in APE1 may associated with early onset of lung cancer as well as some specific subtype of lung cancer
20354815 Observational study of gene-disease association. (HuGE Navigator)
19773279 Observational study of gene-disease association. (HuGE Navigator)
19734419 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
19692168 Observational study of gene-disease association. (HuGE Navigator)
19257887 Observational study of gene-disease association. (HuGE Navigator)
19246451 ASPP2 primarily binds to the core domain of p53, whereas iASPP predominantly interacts with a linker region adjacent to the core domain.
19116388 Observational study and meta-analysis of gene-disease association. (HuGE Navigator)
18798069 Inhibition of expression of iASPP may resume the ability of p53 to induce apoptosis in MCF-7 cells.
18588689 We expect the marker RAI-3'd1 to be (part of) the cause for the association of the chromosome 19q13.3 region's association with cancer
18588689 Observational study of gene-disease association. (HuGE Navigator)
18289367 No consistent association between RAI polymorphism, the haplotype and risk of colorectal cancer has been found.
18289367 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
18275817 High-resolution crystal structure for the C terminus of iASPP, comprised of four ankyrin repeats and an SH3 domain.
18201273 3-dimensional structure of RelA-associated inhibitor in complex with p53 using computational chemistry.
17906639 Data suggest that Pin1 is required for efficient loading of p53 on target promoters upon stress, and that after phosphorylation of p53 triggered by cytotoxic stimuli, Pin1 mediates p53's dissociation from iASPP, promoting cell death.
17872376 Data show here that RAI mRNA expression in human increased as gestation proceeded and that RAI was localized mainly in the syncytiotrophoblast throughout pregnancy.
17570360 RAI induction is necessary but not sufficient for apoptosis induction in non-transformed cells.
17391696 iASPP-SV is a nuclear protein, and is capable of binding to p53 in vivo. Overexpression of iASPP-SV can inhibit the transcriptional activity of p53 on the promoters of both Bax and p21.
17222938 Observational study of gene-environment interaction and pharmacogenomic / toxicogenomic. (HuGE Navigator)
17131345 Observational study of gene-disease association. (HuGE Navigator)
16964264 iASPP binds to and regulates the activity of p53 Pro72 variant more efficiently than that of p53 Arg72
16817948 Observational study of gene-disease association. (HuGE Navigator)
16817948 The RAI polymorphism showed a trend towards risk reduction for both adenomas (OR of 0.70, 95% CI 0.49-1.01) and carcinomas (OR of 0.49, 95% CI 0.21-1.13) among wo
16690207 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
16139958 role of ASPP1, ASPP2, and iASPP as apoptotic specific regulators of p53 [review]
15885892 neither polymorphisms in several DNA repair genes nor alleles of several polymorphisms in the chromosomal of region 19q13.2-3, encompassing the genes ASE, ERCC1, RAI and XPD, were associated with risk of testicular cancer in Danish patients
15607367 The RAI protein, human is an evolutionarily conserved inhibitor of p53, and its expression is upregulated in human breast carcinomas expressing wild-type p53.
12134007 Effect of RAI on transcription and replication of human immunodeficiency virus type 1 (HIV-1).

AA Sequence 

MDSEAFQSARDFLDMNFQSLAMKHMDLKQMELDTAAAKVDELTKQLESLWSDSPAPPGPQAGPPSRPPRY      1 - 70
SSSSIPEPFGSRGSPRKAATDGADTPFGRSESAPTLHPYSPLSPKGRPSSPRTPLYLQPDAYGSLDRATS     71 - 140
PRPRAFDGAGSSLGRAPSPRPGPGPLRQQGPPTPFDFLGRAGSPRGSPLAEGPQAFFPERGPSPRPPATA    141 - 210
YDAPASAFGSSLLGSGGSAFAPPLRAQDDLTLRRRPPKAWNESDLDVAYEKKPSQTASYERLDVFARPAS    211 - 280
PSLQLLPWRESSLDGLGGTGKDNLTSATLPRNYKVSPLASDRRSDAGSYRRSLGSAGPSGTLPRSWQPVS    281 - 350
RIPMPPSSPQPRGAPRQRPIPLSMIFKLQNAFWEHGASRAMLPGSPLFTRAPPPKLQPQPQPQPQPQSQP    351 - 420
QPQLPPQPQTQPQTPTPAPQHPQQTWPPVNEGPPKPPTELEPEPEIEGLLTPVLEAGDVDEGPVARPLSP    421 - 490
TRLQPALPPEAQSVPELEEVARVLAEIPRPLKRRGSMEQAPAVALPPTHKKQYQQIISRLFHRHGGPGPG    491 - 560
GPEPELSPITEGSEARAGPPAPAPPAPIPPPAPSQSSPPEQPQSMEMRSVLRKAGSPRKARRARLNPLVL    561 - 630
LLDAALTGELEVVQQAVKEMNDPSQPNEEGITALHNAICGANYSIVDFLITAGANVNSPDSHGWTPLHCA    631 - 700
ASCNDTVICMALVQHGAAIFATTLSDGATAFEKCDPYREGYADCATYLADVEQSMGLMNSGAVYALWDYS    701 - 770
AEFGDELSFREGESVTVLRRDGPEETDWWWAALHGQEGYVPRNYFGLFPRVKPQRSKV                771 - 828
//

Text Mined References (92)

PMID Year Title
27173435 2016 An organelle-specific protein landscape identifies novel diseases and molecular mechanisms.
27075368 2016 Genome-wide DNA methylation analysis of transient neonatal diabetes type 1 patients with mutations in ZFP57.
26787707 2016 MicroRNA-140 regulates cell growth and invasion in pancreatic duct adenocarcinoma by targeting iASPP.
26646590 2015 Caspase cleavage of iASPP potentiates its ability to inhibit p53 and NF-?B.
26496610 2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances.
26109723 2015 A Screen for Extracellular Signal-Regulated Kinase-Primed Glycogen Synthase Kinase 3 Substrates Identifies the p53 Inhibitor iASPP.
25917613 2015 NFKB1 common variants and PPP1R13L and CD3EAP in relation to lung cancer risk in a Chinese population.
25691752 2015 iASPP, a previously unidentified regulator of desmosomes, prevents arrhythmogenic right ventricular cardiomyopathy (ARVC)-induced sudden death.
25675294 2015 A pro-apoptotic function of iASPP by stabilizing p300 and CBP through inhibition of BRMS1 E3 ubiquitin ligase activity.
25468996 2014 E-cadherin interactome complexity and robustness resolved by quantitative proteomics.
25341046 2014 Nuclear iASPP may facilitate prostate cancer progression.
25149434 2015 Cytoplasmic iASPP expression as a novel prognostic indicator in oral cavity squamous cell carcinoma.
24997996 2014 Phosphoproteomics combined with quantitative 14-3-3-affinity capture identifies SIRT1 and RAI as novel regulators of cytosolic double-stranded RNA recognition pathway.
24966937 2014 MicroRNA124 regulate cell growth of prostate cancer cells by targeting iASPP.
24855949 2014 A code for RanGDP binding in ankyrin repeats defines a nuclear import pathway.
24777476 2014 iASPP is a novel autophagy inhibitor in keratinocytes.
24668753 2014 Oncogene iASPP enhances self-renewal of hematopoietic stem cells and facilitates their resistance to chemotherapy and irradiation.
24604828 2014 Focused screening of a panel of cancer-related genetic polymorphisms reveals new susceptibility loci for pediatric acute lymphoblastic leukemia.
24405603 2014 [Expressions and clinical significances of iASPP and caspase-9 in esophageal cancer].
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
24140460 2013 HapMap-based study identifies risk sub-region on chromosome 19q13.3 in relation to lung cancer among Chinese.
24129315 2014 Immunoaffinity enrichment and mass spectrometry analysis of protein methylation.
23691514 2013 MicroRNA-124 regulates the proliferation of colorectal cancer cells by targeting iASPP.
23624869 2013 Downregulation of miR-124 promotes the growth and invasiveness of glioblastoma cells involving upregulation of PPP1R13L.
23624123 2013 Effects of PPP1R13L and CD3EAP variants on lung cancer susceptibility among nonsmoking Chinese women.
23623661 2013 Restoring p53 function in human melanoma cells by inhibiting MDM2 and cyclin B1/CDK1-phosphorylated nuclear iASPP.
23528480 2013 Helicobacter pylori infection and expressions of apoptosis-related proteins p53, ASPP2 and iASPP in gastric cancer and precancerous lesions.
23420450 2013 Elevated expression of iASPP correlates with poor prognosis and chemoresistance/radioresistance in FIGO Ib1-IIa squamous cell cervical cancer.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23180017 2013 PPP1R13L variant associated with prognosis for patients with rectal cancer.
23088536 2013 Molecular mechanisms underlying the interaction of protein phosphatase-1c with ASPP proteins.
22815155 2012 Elevated expression of iASPP in head and neck squamous cell carcinoma and its clinical significance.
22814378 2012 N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.
22766503 2012 iASPPsv antagonizes apoptosis induced by chemotherapeutic agents in MCF-7 cells and mouse thymocytes.
22552744 2012 Abnormal expression pattern of the ASPP family of proteins in human non-small cell lung cancer and regulatory functions on apoptosis through p53 by iASPP.
22538442 2012 iASPP inhibits p53-independent apoptosis by inhibiting transcriptional activity of p63/p73 on promoters of proapoptotic genes.
22351191 2012 Hapmap-based evaluation of ERCC2, PPP1R13L, and ERCC1 and lung cancer risk in a Chinese population.
22335888 2012 A specific diplotype defined by PPP1R13L rs1970764, CD3EAP rs967591 and ERCC1 rs11615 and lung cancer risk in a Chinese population.
22321011 Protein phosphatase 1? interacting proteins in the human brain.
21998301 2011 Inhibitory member of the apoptosis-stimulating proteins of the p53 family (iASPP) interacts with protein phosphatase 1 via a noncanonical binding motif.
21926165 2011 iASPP and chemoresistance in ovarian cancers: effects on paclitaxel-mediated mitotic catastrophe.
21897369 2011 iASPP/p63 autoregulatory feedback loop is required for the homeostasis of stratified epithelia.
21625267 2011 Inhibitory member of the apoptosis-stimulating protein of p53 (ASPP) family promotes growth and tumorigenesis in human p53-deficient prostate cancer cells.
21513714 2011 The ASPP proteins complex and cooperate with p300 to modulate the transcriptional activity of p53.
21391736 2011 Down-regulation of iASPP in human hepatocellular carcinoma cells inhibits cell proliferation and tumor growth.
21269460 2011 Initial characterization of the human central proteome.
21192816 2010 iASPP is over-expressed in human non-small cell lung cancer and regulates the proliferation of lung cancer cells through a p53 associated pathway.
21184255 2011 RNA interference-mediated silencing of iASPP induces cell proliferation inhibition and G0/G1 cell cycle arrest in U251 human glioblastoma cells.
21046104 2011 The importance of a sub-region on chromosome 19q13.3 for prognosis of multiple myeloma patients after high-dose treatment and stem cell support: a linkage disequilibrium mapping in RAI and CD3EAP.
20840860 2010 p53 and PPP1R13L (alias iASPP or RAI) form a feedback loop to regulate genotoxic stress responses.
20600029 2010 Increased expression of iASPP, regulated by hepatitis B virus X protein-mediated NF-?B activation, in hepatocellular carcinoma.
20422457 2010 Polymorphisms in apoptosis-related genes and survival of patients with early-stage non-small-cell lung cancer.
20354815 2011 Genetic polymorphisms in ATM, ERCC1, APE1 and iASPP genes and lung cancer risk in a population of southeast China.
20068231 2010 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
19773279 2009 Association between genetic variants in VEGF, ERCC3 and occupational benzene haematotoxicity.
19734419 2009 A polymorphism in NFKB1 is associated with improved effect of interferon-{alpha} maintenance treatment of patients with multiple myeloma after high-dose treatment with stem cell support.
19692168 2010 Genetic susceptibility to distinct bladder cancer subphenotypes.
19690332 2009 Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.
19257887 2009 Haplotype frequencies in a sub-region of chromosome 19q13.3, related to risk and prognosis of cancer, differ dramatically between ethnic groups.
19246451 2009 Insight into the structural basis of pro- and antiapoptotic p53 modulation by ASPP proteins.
19116388 2009 A field synopsis on low-penetrance variants in DNA repair genes and cancer susceptibility.
18985028 2008 Hepatitis C virus infection protein network.
18798069 2008 Effect of RNA interference of iASPP on the apoptosis in MCF-7 breast cancer cells.
18691976 2008 Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18588689 2008 Linkage disequilibrium mapping of a breast cancer susceptibility locus near RAI/PPP1R13L/iASPP.
18289367 2008 A haplotype of polymorphisms in ASE-1, RAI and ERCC1 and the effects of tobacco smoking and alcohol consumption on risk of colorectal cancer: a Danish prospective case-cohort study.
18275817 2008 Biochemical and structural studies of ASPP proteins reveal differential binding to p53, p63, and p73.
18201273 2008 Molecular docking analysis of the protein-protein interaction between RelA-associated inhibitor and tumor suppressor protein p53 and its inhibitory effect on p53 action.
17906639 2007 The prolyl isomerase Pin1 orchestrates p53 acetylation and dissociation from the apoptosis inhibitor iASPP.
17872376 2007 Involvement of RelA-associated inhibitor in regulation of trophoblast differentiation via interaction with transcriptional factor specificity protein-1.
17570360 2007 Expression of the RAI gene is conducive to apoptosis: studies of induction and interference.
17391696 2007 Identification of a novel isoform of iASPP and its interaction with p53.
17222938 2007 Genetic polymorphisms and treatment response in advanced non-small cell lung cancer.
17131345 2007 Polymorphisms in the genes ERCC2, XRCC3 and CD3EAP influence treatment outcome in multiple myeloma patients undergoing autologous bone marrow transplantation.
17081983 2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.
16964264 2006 iASPP preferentially binds p53 proline-rich region and modulates apoptotic function of codon 72-polymorphic p53.
16964243 2006 A probability-based approach for high-throughput protein phosphorylation analysis and site localization.
16817948 2006 Effects of polymorphisms in ERCC1, ASE-1 and RAI on the risk of colorectal carcinomas and adenomas: a case control study.
16690207 2007 Gene-environment interactions between smoking and a haplotype of RAI, ASE-1 and ERCC1 polymorphisms among women in relation to risk of lung cancer in a population-based study.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16139958 2005 ASPP--Apoptotic specific regulator of p53.
15885892 2005 Polymorphisms in RAI and in genes of nucleotide and base excision repair are not associated with risk of testicular cancer.
15661756 2005 A mutation in NFkB interacting protein 1 results in cardiomyopathy and abnormal skin development in wa3 mice.
15607367 2005 The expression of iASPP in acute leukemias.
15489900 2004 The N-terminus of a novel isoform of human iASPP is required for its cytoplasmic localization.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15231748 2004 Functional proteomics mapping of a human signaling pathway.
12524540 2003 iASPP oncoprotein is a key inhibitor of p53 conserved from worm to human.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12134007 2002 RelA-associated inhibitor blocks transcription of human immunodeficiency virus type 1 by inhibiting NF-kappaB and Sp1 actions.
10336463 1999 Identification of a novel inhibitor of nuclear factor-kappaB, RelA-associated inhibitor.