| Function |
Multifunctional protein that plays a central role in the cellular response to oxidative stress. The two major activities of APEX1 in DNA repair and redox regulation of transcriptional factors. Functions as a apurinic/apyrimidinic (AP) endodeoxyribonuclease in the DNA base excision repair (BER) pathway of DNA lesions induced by oxidative and alkylating agents. Initiates repair of AP sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone immediately adjacent to the damage, generating a single-strand break with 5'-deoxyribose phosphate and 3'-hydroxyl ends. Does also incise at AP sites in the DNA strand of DNA/RNA hybrids, single-stranded DNA regions of R-loop structures, and single-stranded RNA molecules. Has a 3'-5' exoribonuclease activity on mismatched deoxyribonucleotides at the 3' termini of nicked or gapped DNA molecules during short-patch BER. Possesses a DNA 3' phosphodiesterase activity capable of removing lesions (such as phosphoglycolate) blocking the 3' side of DNA strand breaks. May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation. Acts as a loading factor for POLB onto non-incised AP sites in DNA and stimulates the 5'-terminal deoxyribose 5'-phosphate (dRp) excision activity of POLB. Plays a role in the protection from granzymes-mediated cellular repair leading to cell death. Also involved in the DNA cleavage step of class switch recombination (CSR). On the other hand, APEX1 also exerts reversible nuclear redox activity to regulate DNA binding affinity and transcriptional activity of transcriptional factors by controlling the redox status of their DNA-binding domain, such as the FOS/JUN AP-1 complex after exposure to IR. Involved in calcium-dependent down-regulation of parathyroid hormone (PTH) expression by binding to negative calcium response elements (nCaREs). Together with HNRNPL or the dimer XRCC5/XRCC6, associates with nCaRE, acting as an activator of transcriptional repression. Stimulates the YBX1-mediated MDR1 promoter activity, when acetylated at Lys-6 and Lys-7, leading to drug resistance. Acts also as an endoribonuclease involved in the control of single-stranded RNA metabolism. Plays a role in regulating MYC mRNA turnover by preferentially cleaving in between UA and CA dinucleotides of the MYC coding region determinant (CRD). In association with NMD1, plays a role in the rRNA quality control process during cell cycle progression. Associates, together with YBX1, on the MDR1 promoter. Together with NPM1, associates with rRNA. Binds DNA and RNA. |
| Gene References into Functions |
- Study identified that APEX1 rs2307486 variants conferred an increased risk of mercaptopurine-related early onset neutropenia in pediatric acute lymphoblastic leukemia. PMID: 28882023
- The redox domain of APE1 is necessary for the active mode of stimulation of DNA glycosylases (OGG1, MPG, MBD4). APE1-catalyzed oligomerization along DNA induces helix distortions, which in turn enable conformational selection and stimulation of DNA glycosylases. PMID: 29475157
- APE1 removes 3' mismatches and DNA damage by placing the 3' group within the intra-helical DNA cavity via a non-base flipping mechanism. PMID: 29374164
- This study identified 2837 genes whose expression is significantly changed following APE1 knockdown in pancreatic ductal adenocarcinoma. PMID: 28922540
- MCP- and CP-induced oxidative stress alters APE1-dependent BER-pathway and also mediates cell survival signalling mechanisms via APE1 regulation, thereby promoting lung cancer cell survival and proliferation. PMID: 28887667
- Study uncovered a novel interaction between APE1 and PRDX1, which existed in both the nuclear and cytosolic fractions. The loss of APE1 interaction with PRDX1 promotes APE1 redox function to activate binding of the transcription factor NF-kappaB onto the promoter of IL-8 involved in cancer invasion and metastasis, resulting in its upregulation. PMID: 27388124
- APE1 contributes to the protective effects of resveratrol against neonatal hypoxicischemic brain injuries, and suggest that DNA repair enzymes, including APE1, may be a unique strategy for neuroprotection against this disease. PMID: 29039534
- Studied the association between single-nucleotide polymorphism of apurinic/apyrimidinic endonuclease 1 (APEX1) rs1760944 and risk of nasopharyngeal carcinoma in a Chinese population. PMID: 28464393
- this study demonstrates a novel role of extracellular APE1 in IL-6-dependent cellular responses. PMID: 28751279
- Our results showed that DNA base excision repair proteins APE-1 and XRCC-1 are overexpressed in tongue squamous cell carcinoma and that XRCC-1 is associated with better clinical staging and nodal status. PMID: 27925687
- For the first time, this work identifies Ref-1 as a novel molecular effector in T-ALL and demonstrates that Ref-1 redox inhibition results in potent inhibition of leukemia T cells, including relapsed T-ALL. These data also support E3330 as a specific Ref-1 small-molecule inhibitor for leukemia PMID: 28446640
- Apurinic/apyrimidinic endonuclease 1 is downregulated in Pleomorphic Adenomas of salivary gland and overexpressed in Carcinoma ex Pleomorphic Adenomas, the increased expression of this protein is associated with a more aggressive behavior in Carcinoma ex Pleomorphic Adenomas, which suggests that this protein may represent a prognostic biomarker in the studied Salivary Gland Tumors. PMID: 28523411
- our study demonstrates that elevation of acetylation level of APE1 in tumor could be a novel mechanism by which cells handle the elevated levels of DNA damages in response to genotoxic stress and maintain sustained proliferation. PMID: 27655688
- The chemotherapy-naive serum APE1 level, which correlated with its tissue level inversely associated with progression-free survival of platinum-containing doublet chemotherapy, whereas post-treatment serum APE1 level was inversely associated with overall survival. PMID: 27813497
- HOGG1 Ser326Cys, APE1 Asp148Glu and XRCC1 Arg399Gln polymorphisms are correlated with the risk and clinicopathological features of PACG. PMID: 28396513
- Through the characterization of the interactomes of APE1 with RNA and other proteins, we demonstrate here a role for APE1 in pri-miRNA processing and stability via association with the DROSHA-processing complex during genotoxic stress. We also show that endonuclease activity of APE1 is required for the processing of miR-221/222 in regulating expression of the tumor suppressor PTEN. PMID: 28986522
- the APEX1 Asp148Glu polymorphism might be important in stimulating the development of prostate cancer rather than its invasiveness in various populations, especially for Asians. PMID: 27248666
- our data reinforce the concept that non-synonymous APE1 variants present in the human population may act as cancer susceptibility alleles PMID: 27050370
- Data suggest that APE1 could be a potential target for NSCLC metastasis and AT101 is a potent inhibitor in further treatment of NSCLC patients. PMID: 27074577
- Our findings suggest that constitutive overexpression of APE1 in esophageal adenocarcinoma may be an adaptive pro-survival mechanism that protects against the genotoxic lethal effects of bile reflux episodes. PMID: 26934647
- our study demonstrates that increased acetylation levels of APE1 in tumor cells inhibit the limited N-terminal proteolysis of APE1 and thereby maintain the functions of APE1 to promote tumor cells' sustained proliferation and survival. PMID: 26981776
- Data indicate that apurinic/apyrimidinic endonuclease-1 (APE1) efficiently process an abasic ribonucleoside 5'-monophosphates (rNMPs) site in DNA and have weak endoribonuclease and 3'-exonuclease activities on r8oxoG substrate. PMID: 28977421
- These results suggested that the expression of APE1 was an important basis for the maintenance of poly (ADP-ribose) polymerase 1, and the deletion of APE1 may be related to the resistance of triple-negative breast cancer to olaparib. PMID: 29064327
- Alleles in mitochondrial transcription factor A (TFAM) and AP endonuclease 1 (APE1) are associated with reduced cognitive performance. PMID: 28242328
- Study shows that TRX1 and APEX1 expressions are up regulated in new Multiple Sclerosis (MS) patients compared to controls and might be implicated in pathogenesis of the disease. PMID: 28844667
- Ku antigen displays the AP lyase activity on a certain type of double-stranded DNA. PMID: 27129632
- study demonstrates that APE1 overexpression is an independent prognostic marker, but exclusively in ERG-negative prostate cancers PMID: 28467610
- These results suggest that degradation of endogenous APE1 by Parkin occur when cells are stressed to activate Parkin, and imply a role of Parkin in maintaining the quality of APE1, and loss of Parkin may contribute to elevated APE1 levels in glioblastoma. PMID: 27148961
- The efficiency of AP site cleavage by APE1 was affected by the benzo[a]pyrenyl-DNA adduct (BPDE-dG) in the opposite strand. PMID: 28065385
- Enforced expression of hOGG1 and hAPE significantly protected thalamic neurons and motor neurons from retrograde apoptosis induced by target deprivation and axotomy. PMID: 27364693
- This study supported the hypothesis that the APE1 rs1760944 T>G polymorphism may be associated with N,N-dimethylformamide -induced abnormal liver function in the Chinese Han population. PMID: 27463724
- Repair of the uracil adjacent to cisplatin ICLs proceeds through the classical BER pathway, highlighting the importance of specific proteins in this redundant pathway. Removal of uracil is followed by the generation of an abasic site and subsequent cleavage by AP endonuclease 1 (APE1). Inhibition of either the repair or redox domain of APE1 gives rise to cisplatin resistance. PMID: 28110804
- Overexpressed APE1 promotes ovarian cancer growth and metastasis. Downregulated APE1 could suppress cell activity via AP-1 pathway, suggesting that APE1 gene may be a potential therapeutic target for ovarian cancer. PMID: 27553367
- Our results indicate that the tumor-associated APE1 R237C variant is a possible susceptibility factor, but not likely a driver of cancer cell phenotypes. PMID: 28181292
- Association of the APE1 single nucleotide polymorphism rs3136820 and the levels of abasic sites in human leukocytes derived from breast cancer patients PMID: 27539671
- APE1 acetylation is an integral part of the base excision repair pathway for maintaining genomic integrity. PMID: 27994014
- Effects of monovalent (K(+)) and divalent (Mg(2+), Mn(2+), Ca(2+), Zn(2+), Cu(2+), and Ni(2+)) metal ions on DNA binding and catalytic stages of APEX1 were studied. PMID: 27063150
- Individuals with the variant TG genotypes had a significantly increased risk of female infertility. Whereas, a significant association between 1349T > G polymorphism and female infertility risk was not observed. PMID: 26790616
- APE1 Accelerates turnover of OGG1 by preventing retrograde binding to the abasic-site product. PMID: 28345889
- The results demonstrate a crucial role of APE1 3' to 5' exonuclease activity in combating mutations in CpG clusters caused by an intermediate of DNA demethylation during base excision repair. PMID: 27183823
- In an in vivo model of restenosis, which is characterized by oxidative stress, endothelial activation, and smooth muscle cell proliferation, Thioredoxin-1 protein levels are reduced in the endothelium of the carotids. APEX1 acts anti-apoptotic in endothelial cells. This anti-apoptotic effect depends on the first 20 amino acids of APEX1 PMID: 27835927
- While DNA conformational alteration is negligible, APE1 enzyme shows characteristic changes in the alpha helix and beta strand ratio after incubation with G. lucidum extract. The enhanced reactivity of APE1 at the molecular level in the presence of G. lucidium is attributed to this effect. PMID: 27240987
- These results strongly indicate that anti-inflammatory effects in TNF-alpha-stimulated endothelial cells by acetylation are tightly linked to secreted APE1/Ref-1, which inhibits TNF-alpha binding to TNFR1 by reductive conformational change, with suggestion as an endogenous inhibitor of vascular inflammation. PMID: 26964514
- Polymorphism in XRCC1 and APE1 gene is associated with an increased risk of COPD. PMID: 27107596
- Data indicate conserved amino acid residues in the nucleotide incision repair (NIR)-specific enzymes of human APE1 and Bacillus subtilis ExoA.. PMID: 27343627
- Based on these results, we conclude that the APEX gene polymorphism Ile64Val may be associated with an increased risk of colorectal cancer. PMID: 26146106
- Serum levels of APE1/Ref-1 in bladder cancer patients were significantly elevated compared to those of the control group. Serum APE1/Ref-1 levels are associated with tumor stage, grade, muscle invasion, and recurrence. PMID: 25672588
- OGG1 and APE1 polymorphisms are associated with stage- and sex-specific risk of colorectal carcinoma in the Taiwanese population. PMID: 27022219
- Our study suggested that the APE1 protein is important for the proliferation and growth of ovarian cancer cells. APE1 silencing might enhance drug-sensitivity, and thus APE1 might serve as a novel anti-OC therapeutic target. PMID: 27802207
- Our study identified that the APE1 -656 T>G polymorphism may contribute to the susceptibility of noise-induced hearing loss. PMID: 26507517
- AP Endonuclease 1 as a Key Enzyme in Repair of Apurinic/Apyrimidinic Sites. PMID: 27682167
- Antiapoptotic APE1-cardiac progenitor cell grafts, which increased TAK1-NF-kappaB pathway activation, survived effectively in the ischemic heart, restored cardiac function, and reduced cardiac inflammation and fibrosis. APE1 overexpression in CPCs may serve as a novel strategy to improve cardiac cell therapy. PMID: 27334489
- The APE1-141 G/G genotype seems to have a protective role against cataract, and the T allele seems to have a deleterious role in the development of cataract. PMID: 26884880
- Study shows that APE1/Ref-1 levels were significantly elevated in bladder cancer (BCa) patients relative to levels in non-BCa controls and were correlated with tumor grade and stage. These results suggest that APE1 would be a good biomarker for diagnosis of BCa. PMID: 27057081
- Findings indicated that individuals with APEX1 variant TG genotypes had a significant decreased risk of breast cancer, however, the significant association between 1349T>G polymorphism and breast cancer risk was not observed. PMID: 26314200
- The data from this study indicates that the ApE1 1349T>G polymorphism is associated with increased risk of prostate cancer. PMID: 26255264
- reduced activity in Alzheimer disease PMID: 26539816
- The findings suggest that the c.-468 T>G polymorphism of the APEX1 gene may play a role in the pathogenesis of keratoconus. PMID: 26204393
- a possible role of APE1/Ref-1 over-expression both in hepatocyte survival and HCC development PMID: 26624999
- XPC interacts physically with APE1 and XPC regulates APE1 expression. PMID: 26811994
- a novel mechanism of p53 degradation through an APE1-mediated, redox-dependent pathway. PMID: 26032169
- Study elucidates the function of Ape1 in pancreatic cancer cells and demonstrates crosstalk between the Ape1-mediated redox signaling and WNT signaling pathways. PMID: 26081414
- Since APE1, XRCC1 and POLB proteins operate downstream the same DNA repair pathway to eliminate DNA oxidative damage, their expression above basal levels found in our study could reveal excessive oxidative stress in high-grade bladder tumors. PMID: 26238022
- The deregulation of PD-L1 and APE1 might contribute to the development and the poor prognosis of gastric cancer. PMID: 25733810
- Our results implicate APE1 in novel molecular interactions that regulate early stress responses elicited by microbial infections. PMID: 26761793
- Genotypic analysis of APE1 (rs1130409) showed statistically significant association of Asp148Glu with elevated susceptibility to breast cancer. PMID: 26257461
- results of this meta-analysis collectively suggest that APE1 gene Asp148Glu variant is not a risk-conferring factor for digestive cancer. Further large and well-designed studies are required PMID: 26292623
- Lack of aprataxin impairs mitochondrial functions via downregulation of the APE1/NRF1/NRF2 pathway. PMID: 25976310
- Inhibition of APE1 may present a novel therapeutic approach for the treatment of hepatocellular carcinoma PMID: 25976295
- Our data suggest that the -656T>G ApE1 polymorphism may be associated with increased risk of idiopathic male infertility PMID: 25917483
- the current evidence indicates that APE1 regulates angiogenesis in osteosarcoma by controlling the transforming growth factor beta pathway, suggesting a novel target for anti-angiogenesis therapy in human osteosarcoma. PMID: 26250694
- Results show that APE1 plays an important role in temozolomide resistance of glioblastoma cells. Its down-regulation sensitizes the cells to the cytotoxic effects of temozolomide. PMID: 26520369
- Review/Meta-analysis: APE1 Asp148Glu polymorphism G allele is associated with an increased GI cancer risk, especially in gastric cancer. PMID: 25945024
- The XPD Asp312Asn and APE1 Asp148Glu polymorphisms increase the risk for HNC. PMID: 25916209
- Extreme expression of APE1 in malignant tumors was observed, suggesting that breast cancer cells may require APE1 for survival. PMID: 26359670
- The results indicate that low APE1 activity is associated with lung cancer risk, consistent with the hypothesis that 'bad DNA repair', rather than 'bad luck', is involved in cancer etiology. PMID: 26045303
- these data provide the first evidence that a critical BER enzyme, APE1, helps regulate the NER pathway in the repair of cisplatin damage in sensory neurons. PMID: 26164266
- increases in APEX1 level confer protection against the murine paternal age effect, thus highlighting the role of APEX1 in preserving reproductive health with increasing age and in protection against genotoxin-induced mutagenesis in somatic cells PMID: 26201249
- Two natural variants of APE1 have a greater reduction of nuclease activity on nucleosomes. PMID: 26134573
- variant alleles in the NEIL2 (rs804270), APE1 (rs2275008), CYP2E1 (rs2031920) and MDM2 (rs2279744) SNPs may independently influence susceptibility to gastric cancer in a Northern Jiangsu Chinese population. PMID: 26373042
- REF1 polymorphism is unlikely to be associated with colorectal cancer risk PMID: 25344644
- Oxidative DNA damage increases in lenses with age-related cataract, and the three BER enzymes compensatively increase in the LECs, while decreasing in the opaque cortex. PMID: 24911554
- Results show that YB-1 interferes negatively with the AP site DNA cleavage activity of both APE1 and NEIL1 for ssDNA and bubble structures. PMID: 25605055
- showed evidence on interaction between APEX1 148Glu variant and cigarette smoking in increasing lung cancer susceptibility among male Chinese PMID: 25156607
- These results suggested that APE1 controls the organization of actin cytoskeleton through the regulation of TGF-beta1 expression, providing novel insights into the biological significance of APE1. PMID: 25858321
- The APEX1 Asp(148)Glu genotype correlates well with its mRNA and protein expression among endometriosis patients. PMID: 25422360
- APE1 activity in nucleosomes, like base excision repair glycosylases, is primarily regulated by its chance interactions with transiently exposed lesions. PMID: 25847267
- The neighboring bases of the abasic sites in the complementary DNA strand were found to have significant contribution in addition to the flanking bases in modulating APE1 activity. PMID: 25847273
- A novel method for monitoring functional lesion-specific recruitment of repair proteins in live cells. PMID: 25879709
- APEX1 mutations are associated with increased breast cancer. PMID: 25292033
- The cysteine variants do not interfere with APE1 DNA repair functions. PMID: 25108836
- The polymorphism T2197G, GG genotype APE1 carriers exhibited a significantly reduced expression of genes of the BER repair system. PMID: 25268610
- These results define a novel role of APE/Ref-1 in HCC progression as being an important mediating and potentiating molecule, and also provide a basis for further investigations utilizing appropriate APE/Ref-1 inhibitors PMID: 25109342
- APE1 Asp148Glu is associated with increased colorectal cancer risk in the Chinese Han population. PMID: 25024628
- Apurinic/apyrimidinic endonuclease/redox factor-1 (APE1/Ref-1) redox function negatively regulates NRF2 PMID: 25492865
- This meta-analysis suggested that the APE1 Asp148Glu polymorphism was a risk factor for prostate cancer susceptibility in Hospital-based population. PMID: 25234162
- findings have suggested that APE1, XRCC3, XPD, and hOGG1 gene variants could facilitate the development of migraine disease. PMID: 24892639
- APE1 possesses the ability to remove a phosphoryl group from the 3' end of RNA decay products and has weak 3'-5' exoribonuclease activity. PMID: 25498387
- Advanced non-small cell lung cancer patients with both APE1- and excision repair cross-complementing 1 -negative tumors had higher response rate to platinum-paclitaxel chemotherapy , longer progression-free survival and overall survival. PMID: 25107571
- This review discusses APE1 nature in various human etiologies, including neurodegeneration, cancer, cardiovascular and other diseases that have been linked with alterations in the expression, subcellular localization and activities of APE. [review] PMID: 25033834
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| Subcellular Location |
Nucleus, Nucleus, nucleolus, Nucleus speckle, Endoplasmic reticulum, Cytoplasm, Note=Detected in the cytoplasm of B-cells stimulated to switch (By similarity), Colocalized with SIRT1 in the nucleus, Colocalized with YBX1 in nuclear speckles after genotoxic stress, Together with OGG1 is recruited to nuclear speckles in UVA-irradiated cells, Colocalized with nucleolin and NPM1 in the nucleolus, Its nucleolar localization is cell cycle dependent and requires active rRNA transcription, Colocalized with calreticulin in the endoplasmic reticulum, Translocation from the nucleus to the cytoplasm is stimulated in presence of nitric oxide (NO) and function in a CRM1-dependent manner, possibly as a consequence of demasking a nuclear export signal (amino acid position 64-80), S-nitrosylation at Cys-93 and Cys-310 regulates its nuclear-cytosolic shuttling, Ubiquitinated form is localized predominantly in the cytoplasm, SUBCELLULAR LOCATION: DNA-(apurinic or apyrimidinic site) lyase, mitochondrial: Mitochondrion |
