APEX1

Summary

Gene Symbol: APEX1
Description: apurinic/apyrimidinic endodeoxyribonuclease 1
Alias: APE, APE1, APEN, APEX, APX, HAP1, REF1, DNA-(apurinic or apyrimidinic site) lyase, AP endonuclease class I, AP lyase, APEX nuclease (multifunctional DNA repair enzyme) 1, apurinic-apyrimidinic endonuclease 1, apurinic/apyrimidinic (abasic) endonuclease, deoxyribonuclease (apurinic or apyrimidinic), protein REF-1, redox factor-1
Species: human

Top Publications

  1. ncbi Genetic polymorphisms in the base excision repair pathway and cancer risk: a HuGE review
    Rayjean J Hung
    Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France
    Am J Epidemiol 162:925-42. 2005
  2. pmc Human apurinic/apyrimidinic endonuclease 1
    Mengxia Li
    Intramural Research Program, Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland
    Antioxid Redox Signal 20:678-707. 2014
  3. ncbi DNA-bound structures and mutants reveal abasic DNA binding by APE1 and DNA repair coordination [corrected]
    C D Mol
    Skaggs Institute for Chemical Biology, and the Department of Molecular Biology, La Jolla, California 92037 1027, USA
    Nature 403:451-6. 2000
  4. ncbi Polymorphisms of DNA repair genes and risk of non-small cell lung cancer
    Shanbeh Zienolddiny
    Department of Toxicology, National Institute of Occupational Health, Oslo, Norway
    Carcinogenesis 27:560-7. 2006
  5. pmc APE1/Ref-1 interacts with NPM1 within nucleoli and plays a role in the rRNA quality control process
    Carlo Vascotto
    Department of Biomedical Sciences and Technologies, University of Udine, P le Kolbe 4, 33100 Udine, Italy
    Mol Cell Biol 29:1834-54. 2009
  6. pmc Characterization of abasic endonuclease activity of human Ape1 on alternative substrates, as well as effects of ATP and sequence context on AP site incision
    Brian R Berquist
    Unit of Structure and Function in Base Excision Repair, Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA
    J Mol Biol 379:17-27. 2008
  7. doi Polymorphisms in genes of APE1, PARP1, and XRCC1: risk and prognosis of colorectal cancer in a northeast Chinese population
    Ye Li
    Department of Epidemiology, Public Health College, Harbin Medical University, 157 Baojian Street, Nangang District, Harbin, People s Republic of China
    Med Oncol 30:505. 2013
  8. ncbi Human apurinic endonuclease 1 (APE1) expression and prognostic significance in osteosarcoma: enhanced sensitivity of osteosarcoma to DNA damaging agents using silencing RNA APE1 expression inhibition
    Dong Wang
    Section of Hematology Oncology, Department of Pediatrics, Herman B Wells Center for Pediatric Research, 1044 W Walnut, R4 302C, Indianapolis, IN 46202, USA
    Mol Cancer Ther 3:679-86. 2004
  9. pmc Polygenic model of DNA repair genetic polymorphisms in human breast cancer risk
    Tasha R Smith
    Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 1120 NW 14th Street, CRB Building 1511, Miami, FL, USA
    Carcinogenesis 29:2132-8. 2008
  10. doi Association between single-nucleotide polymorphisms of selected genes involved in the response to DNA damage and risk of colon, head and neck, and breast cancers in a Polish population
    K Jelonek
    Department of Experimental and Clinical Radiobiology, Maria Sklodowska Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland
    J Appl Genet 51:343-52. 2010

Research Grants

  1. Cardioscopy New Platform for Less Invasive Surgery on the Beating Heart
    Tomislav Mihaljevic; Fiscal Year: 2013
  2. Intravascular Cardiac Assist System for Decompression and Recovery
    CAITLYN J BOSECKER; Fiscal Year: 2010
  3. ALAN BRENT PACKARD; Fiscal Year: 2014
  4. Daniel Tamez; Fiscal Year: 2014
  5. Myosin Isoforms in Relation to Function in Human Heart
    Richard L Moss; Fiscal Year: 2010
  6. Development of an Implantable "Plug and Play" TransApical to Aorta VAD
    Stephen Topaz; Fiscal Year: 2007
  7. Molecular Epidemiology and Natural History of SIVcpz
    Beatrice H Hahn; Fiscal Year: 2013
  8. Regulations of DNA Alkylation/Deamination Damage Repair
    Rabindra Roy; Fiscal Year: 2013
  9. Kishor K Bhakat; Fiscal Year: 2015
  10. Role of ROS-Induced DNA Damage in Mitochondria-Regulated Apoptosis
    Anne Tann; Fiscal Year: 2012

Detail Information

Publications367 found, 100 shown here

  1. ncbi Genetic polymorphisms in the base excision repair pathway and cancer risk: a HuGE review
    Rayjean J Hung
    Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France
    Am J Epidemiol 162:925-42. 2005
    ..risk, focusing on three key genes: 8-oxoguanine DNA glycosylase (OGG1), apurinic/apyrimidinic endonuclease (APE1/APEX1), and x-ray repair cross-complementing group 1 (XRCC1)...
  2. pmc Human apurinic/apyrimidinic endonuclease 1
    Mengxia Li
    Intramural Research Program, Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland
    Antioxid Redox Signal 20:678-707. 2014
    Human apurinic/apyrimidinic endonuclease 1 (APE1, also known as REF-1) was isolated based on its ability to cleave at AP sites in DNA or activate the DNA binding activity of certain transcription factors...
  3. ncbi DNA-bound structures and mutants reveal abasic DNA binding by APE1 and DNA repair coordination [corrected]
    C D Mol
    Skaggs Institute for Chemical Biology, and the Department of Molecular Biology, La Jolla, California 92037 1027, USA
    Nature 403:451-6. 2000
    ..The biologically critical human base excision repair enzyme APE1 cleaves the DNA sugar-phosphate backbone at a position 5' of AP sites to prime DNA repair synthesis...
  4. ncbi Polymorphisms of DNA repair genes and risk of non-small cell lung cancer
    Shanbeh Zienolddiny
    Department of Toxicology, National Institute of Occupational Health, Oslo, Norway
    Carcinogenesis 27:560-7. 2006
    ..excision repair (NER) genes XPA, ERCC1, ERCC2/XPD, ERCC4/XPF and ERCC5/XPG; base excision repair (BER) genes APE1/APEX, OGG1, MPG, XRCC1, PCNA, POLB, POLiota, LIG3 and EXO1; double-strand break repair (DSB-R) genes XRCC2, XRCC3, XRCC9,..
  5. pmc APE1/Ref-1 interacts with NPM1 within nucleoli and plays a role in the rRNA quality control process
    Carlo Vascotto
    Department of Biomedical Sciences and Technologies, University of Udine, P le Kolbe 4, 33100 Udine, Italy
    Mol Cell Biol 29:1834-54. 2009
    b>APE1/Ref-1 (hereafter, APE1), a DNA repair enzyme and a transcriptional coactivator, is a vital protein in mammals...
  6. pmc Characterization of abasic endonuclease activity of human Ape1 on alternative substrates, as well as effects of ATP and sequence context on AP site incision
    Brian R Berquist
    Unit of Structure and Function in Base Excision Repair, Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA
    J Mol Biol 379:17-27. 2008
    Human Ape1 is a multifunctional protein with a major role in initiating repair of apurinic/apyrimidinic (AP) sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone immediately adjacent to the damage...
  7. doi Polymorphisms in genes of APE1, PARP1, and XRCC1: risk and prognosis of colorectal cancer in a northeast Chinese population
    Ye Li
    Department of Epidemiology, Public Health College, Harbin Medical University, 157 Baojian Street, Nangang District, Harbin, People s Republic of China
    Med Oncol 30:505. 2013
    ..Four single-nucleotide polymorphisms (SNPs) in genes of apurinic/apyrimidinic endonuclease-1 (APE1), ADP-ribosyltransferase (ADPRT, also known as PARP1), and X-ray repair cross-complementing groups 1 (XRCC1) were ..
  8. ncbi Human apurinic endonuclease 1 (APE1) expression and prognostic significance in osteosarcoma: enhanced sensitivity of osteosarcoma to DNA damaging agents using silencing RNA APE1 expression inhibition
    Dong Wang
    Section of Hematology Oncology, Department of Pediatrics, Herman B Wells Center for Pediatric Research, 1044 W Walnut, R4 302C, Indianapolis, IN 46202, USA
    Mol Cancer Ther 3:679-86. 2004
    ..tumor cells to currently used chemotherapeutic treatments, we examined the role of human apurinic endonuclease 1 (APE1) in osteosarcoma tumor cell resistance and prognosis...
  9. pmc Polygenic model of DNA repair genetic polymorphisms in human breast cancer risk
    Tasha R Smith
    Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 1120 NW 14th Street, CRB Building 1511, Miami, FL, USA
    Carcinogenesis 29:2132-8. 2008
    ..single-nucleotide polymorphisms (nsSNPs) in four DNA repair pathways-(i) base excision repair: ADPRT V762A, APE1 D148E, XRCC1 R194W/R280H/R399Q and POLD1 R119H; (ii) nucleotide excision repair: ERCC2 D312N/K751Q, ERCC4 R415Q, ..
  10. doi Association between single-nucleotide polymorphisms of selected genes involved in the response to DNA damage and risk of colon, head and neck, and breast cancers in a Polish population
    K Jelonek
    Department of Experimental and Clinical Radiobiology, Maria Sklodowska Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland
    J Appl Genet 51:343-52. 2010
    ..Here we analysed polymorphisms in 5 genes involved in DNA repair (XPD Asp312Asn and Lys751Gln, XRCC1 Arg399Gln, APE1 Asp148Glu, NBS1 Glu185Gln, and XPA G-4A) and in a gene involved in regulation of the cell-cycle (CCND1 A870G)...
  11. ncbi Human AP endonuclease (APE1) demonstrates endonucleolytic activity against AP sites in single-stranded DNA
    Dina R Marenstein
    Department of Pathology and Kaplan Comprehensive Cancer Center, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA
    DNA Repair (Amst) 3:527-33. 2004
    Human apurinic/apyrimidinic endonuclease (APE1) is an enzyme of DNA base excision repair (BER) which catalyzes endonucleolytic cleavage immediately 5' to abasic (AP) sites...
  12. ncbi Genetic polymorphisms in base-excision repair pathway genes and risk of breast cancer
    Yawei Zhang
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Rockville, Maryland, USA
    Cancer Epidemiol Biomarkers Prev 15:353-8. 2006
    ..We evaluated whether genetic variation in six BER pathway genes (XRCC1, ADPRT, APEX1, OGG1, LIG3, and MUTYH) is associated with breast cancer risk in two large population-based case-control studies ..
  13. doi Association of APE1 and hOGG1 polymorphisms with colorectal cancer risk in a Turkish population
    Emel Canbay
    Basaksehir State Hospital, Department of General Surgery, Basaksehir, Istanbul, Turkey
    Curr Med Res Opin 27:1295-302. 2011
    ..The aim of this study was to investigate the associations between the APE1 Asp148Glu, hOGG1 Ser326Cys, XRCC1 Arg399Gln, XRCC3 Thr241Met, XPD Lys751Gln, XPG Asp1104His polymorphisms and CRC ..
  14. pmc Silencing of APE1 enhances sensitivity of human hepatocellular carcinoma cells to radiotherapy in vitro and in a xenograft model
    Yanping Cun
    Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People s Republic of China
    PLoS ONE 8:e55313. 2013
    ..problem, we investigated the correlation between radioresistance and the human apurinic/apyrimidinic endonuclease (APE1), a bifunctional protein, which plays an important role in DNA repair and redox regulation activity of ..
  15. ncbi Tumor suppressor NM23-H1 is a granzyme A-activated DNase during CTL-mediated apoptosis, and the nucleosome assembly protein SET is its inhibitor
    Zusen Fan
    Center for Blood Research and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
    Cell 112:659-72. 2003
    ..GzmA-activated DNase (GAAD) is in an ER associated complex containing pp32 and the GzmA substrates SET, HMG-2, and Ape1. We show that GAAD is NM23-H1, a nucleoside diphosphate kinase implicated in suppression of tumor metastasis, and ..
  16. pmc Role of the multifunctional DNA repair and redox signaling protein Ape1/Ref-1 in cancer and endothelial cells: small-molecule inhibition of the redox function of Ape1
    Meihua Luo
    Department of Pediatrics Section of Hematology Oncology, Herman B Wells Center for Pediatric Research, Indianapolis, Indiana 46202, USA
    Antioxid Redox Signal 10:1853-67. 2008
    ..Removal of the damaged base creates a baseless (AP) site. AP endonuclease1 (Ape1) acts on this site to continue the BER-pathway repair...
  17. pmc Critical lysine residues within the overlooked N-terminal domain of human APE1 regulate its biological functions
    Damiano Fantini
    Department of Biomedical Sciences and Technologies, University of Udine, 33100 Udine, Italy
    Nucleic Acids Res 38:8239-56. 2010
    Apurinic/apyrimidinic endonuclease 1 (APE1), an essential protein in mammals, is involved in base excision DNA repair (BER) and in regulation of gene expression, acting as a redox co-activator of several transcription factors...
  18. pmc Reduced expression of DNA repair and redox signaling protein APE1/Ref-1 impairs human pancreatic cancer cell survival, proliferation, and cell cycle progression
    Yanlin Jiang
    Department of Pediatrics, Herman B Wells Center for Pediatric Research, Walnut, Indianapolis 46202, USA
    Cancer Invest 28:885-95. 2010
    ..Understanding the chemoresistance intrinsic to this cancer will aid in developing new regimens. High expression of APE1/Ref-1, a DNA repair and redox signaling protein, is associated with resistance, poor outcome, and angiogenesis; ..
  19. pmc Apurinic/apyrimidinic endonuclease 1 is the essential nuclease during immunoglobulin class switch recombination
    Shahnaz Masani
    Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA
    Mol Cell Biol 33:1468-73. 2013
    ..Although it is presumed that the apurinic/apyrimidinic endonuclease 1 (APE1) generates DNA strand incisions (a prerequisite for CSR) at these abasic sites, a direct test of the requirement ..
  20. pmc Association and interactions between DNA repair gene polymorphisms and adult glioma
    Yanhong Liu
    Department of Epidemiology, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Cancer Epidemiol Biomarkers Prev 18:204-14. 2009
    ..the single-locus analysis, six single-nucleotide polymorphisms [ERCC1 3' untranslated region (UTR), XRCC1 R399Q, APEX1 E148D, PARP1 A762V, MGMT F84L, and LIG1 5'UTR] showed a significant association with glioma risk...
  21. ncbi Apurinic/apyrimidinic endonuclease activity is elevated in human adult gliomas
    M S Bobola
    Department of Neurological Surgery, University of Washington, 1959 N E Pacific Street, Seattle, WA 98195, USA
    Clin Cancer Res 7:3510-8. 2001
    ..The major Ap endo in human cells is Ape1, an abundant multi-functional protein also known as Ref-1, Hap-1, and Apex...
  22. ncbi Polymorphisms in genes of nucleotide and base excision repair: risk and prognosis of colorectal cancer
    Victor Moreno
    Institut d Investigacio Biomedica de Bellvitge, Institut Catala d Oncologia, Hospitalet, Barcelona, Spain
    Clin Cancer Res 12:2101-8. 2006
    ..We have undertaken a comprehensive study of common polymorphisms in genes of DNA repair, exploring both the risk of developing colorectal cancer and the prognosis of patients...
  23. ncbi Association between polymorphisms in the DNA repair genes, XRCC1, APE1, and XPD and acute side effects of radiotherapy in breast cancer patients
    Jenny Chang-Claude
    Division of Clinical Epidemiology and Toxicology, German Cancer Research Center, Heidelberg, Germany
    Clin Cancer Res 11:4802-9. 2005
    ..We evaluated the association of six polymorphisms in the DNA repair genes: XRCC1 (Arg194Trp, Arg280His, and Arg399Gln), APE1 (Asp148Glu), and XPD (Lys751Gln and Asp312Asn), with the risk of acute skin reactions following radiotherapy.
  24. ncbi DNA repair genetic polymorphisms and risk of colorectal cancer in the Czech Republic
    B Pardini
    Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 14220 Prague 4, Czech Republic
    Mutat Res 638:146-53. 2008
    ..Data analysis showed that the variant allele homozygotes for the Asn148Glu polymorphism in the APE1 gene were at a statistically non-significant increased risk of colorectal cancer...
  25. ncbi Histology-specific expression of a DNA repair protein in pediatric rhabdomyosarcomas
    B Thomson
    Department of Pediatrics, Indiana University School of Medicine, Indianapolis, USA
    J Pediatr Hematol Oncol 23:234-9. 2001
    ..The enzyme apurinic/apyrimidinic endonuclease/redox factor 1 (APE/ref1), a key protein in the base excision repair pathway, displays both repair and redox control...
  26. ncbi Ape1 abasic endonuclease activity is regulated by magnesium and potassium concentrations and is robust on alternative DNA structures
    David M Wilson
    Laboratory of Molecular Gerontology, GRC, National Institute on Aging, IRP, NIH, 5600 Nathan Shock Drive, Baltimore, MD 21224 6825, USA
    J Mol Biol 345:1003-14. 2005
    Abasic lesions are common mutagenic or cytotoxic DNA damages. Ape1 is the major human apurinic/apyrimidinic (AP) endonuclease and initiates repair of abasic sites by catalyzing strand cleavage at the lesion...
  27. ncbi Association of DNA repair polymorphisms with DNA repair functional outcomes in healthy human subjects
    Pavel Vodicka
    Institute of Experimental Medicine, Videnska 1083, 14200, Academy of Sciences of the Czech Republic, Prague, Czech Republic
    Carcinogenesis 28:657-64. 2007
    ..of genotype combinations showed that the increasing number of variant alleles for both XRCC1 Arg399Gln and APE1 Asn148Glu polymorphisms resulted in a significant decrease of irradiation-specific repair rates (P=0...
  28. pmc Subcellular localization of APE1/Ref-1 in human hepatocellular carcinoma: possible prognostic significance
    Vittorio Di Maso
    Centro Studi Fegato, AREA Science Park and University of Trieste, Trieste, Italy
    Mol Med 13:89-96. 2007
    b>APE1/Ref-1, normally localized in the nucleus, is a regulator of the cellular response to oxidative stress. Cytoplasmic localization has been observed in several tumors and correlates with a poor prognosis...
  29. doi DNA repair genes in Parkinson's disease
    Mehmet Gencer
    Department of Neurology, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey
    Genet Test Mol Biomarkers 16:504-7. 2012
    ..of these findings, we investigated whether DNA repair gene polymorphisms (XRCC1 Arg399Gln, XRCC3 Thr241Met XPD Lys751Gln, XPG Asp1104His, APE1 Asp148Glu, and HOGG1 Ser326Cys) account for an increased risk of Parkinson's disease (PD).
  30. doi Human AP endonuclease/redox factor APE1/ref-1 modulates mitochondrial function after oxidative stress by regulating the transcriptional activity of NRF1
    Mengxia Li
    Cancer Center and Department of Pathology, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, People s Republic of China
    Free Radic Biol Med 53:237-48. 2012
    ..In this study, we show that the human apurinic/apyrimidinic endonuclease/redox factor (APE1/Ref-1) is involved in mitochondrial function regulation by modulating the DNA-binding activity of NRF1...
  31. pmc The APE1 Asp/Asp genotype and the combination of APE1 Asp/Asp and hOGG1-Cys variants are associated with increased p53 mutation in non-small cell lung cancer
    Chun Hsuan Lin
    Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan, ROC
    J Epidemiol 22:537-42. 2012
    ..polymorphism is associated with lung cancer risk, but there are limited data regarding an association between the APE1 Asp148Glu polymorphism and lung cancer...
  32. doi Association between the OGG1 Ser326Cys and APEX1 Asp148Glu polymorphisms and lung cancer risk: a meta-analysis
    Wu Wei
    Department of Hematology, Peace Hospital of Changzhi Medical College, Changzhi, 046000, China
    Mol Biol Rep 39:11249-62. 2012
    ..data on the association between the 8-oxo-guanine glycosylase-1 (OGG1) and apurinic/apyrimidinic-endonuclease-1 (APEX1/APE1) polymorphisms and lung cancer risk remained controversial...
  33. pmc Lack of an association between two BER gene polymorphisms and breast cancer risk: a meta-analysis
    Bian Wu
    Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    PLoS ONE 7:e50857. 2012
    ..ADPRT and APE1 are two important genes in the BER pathway...
  34. doi Role of the unstructured N-terminal domain of the hAPE1 (human apurinic/apyrimidinic endonuclease 1) in the modulation of its interaction with nucleic acids and NPM1 (nucleophosmin)
    Mattia Poletto
    Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy
    Biochem J 452:545-57. 2013
    ..Although required, however, this region is not sufficient itself to stably interact with DNA or NPM1...
  35. pmc Apurinic/apyrimidinic endonuclease 1 induced upregulation of fibroblast growth factor 2 and its receptor 3 induces angiogenesis in human osteosarcoma cells
    Tao Ren
    Cancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China
    Cancer Sci 105:186-94. 2014
    Tumor angiogenesis contributes to inferior prognosis in osteosarcoma. Apurinic/apyrimidinic endonuclease 1 (APE1) and fibroblast growth factor 2 (FGF2) and its receptor 3 (FGFR3) signaling pathway plays an important role in the angiogenic ..
  36. ncbi Alteration of APE1/ref-1 expression in non-small cell lung cancer: the implications of impaired extracellular superoxide dismutase and catalase antioxidant systems
    Dae Goon Yoo
    Department of Physiology, College of Medicine, Chungnum National University, Jung Gu, Daejeon 301 131, Republic of Korea
    Lung Cancer 60:277-84. 2008
    Apurinic/apyrimidinic endonuclease1/ref-1(APE1/ref-1) is a key enzyme in the base excision repair and in transcriptional modulation against oxidative stress...
  37. pmc Base excision repair genes and risk of lung cancer among San Francisco Bay Area Latinos and African-Americans
    Jeffrey S Chang
    Department of Epidemiology and Biostatistics, Division of Neuroepidemiology, University of California San Francisco, San Francisco, CA 94143 1215, USA
    Carcinogenesis 30:78-87. 2009
    ..examines the association between 24 single-nucleotide polymorphisms (SNPs) belonging to five BER genes (XRCC1, APEX1, PARP1, MUTYH and OGG1) and lung cancer among Latinos (113 cases and 299 controls) and African-Americans (255 ..
  38. pmc Identification of a residue critical for the excision of 3'-blocking ends in apurinic/apyrimidinic endonucleases of the Xth family
    Victor M Castillo-Acosta
    Instituto de Parasitologia y Biomedicina Lopez Neyra, Consejo Superior de Investigaciones Cientificas, Armilla Granada, Spain
    Nucleic Acids Res 37:1829-42. 2009
    ..In human cells, APE1 excises sugar fragments that block the 3'-ends thus facilitating DNA repair synthesis...
  39. ncbi Experimental study enhancing the chemosensitivity of multiple myeloma to melphalan by using a tissue-specific APE1-silencing RNA expression vector
    Zhen Zhou Yang
    Department of Hematology, Xinqiao Hospital, Third Military Medical University, Chongqing, PR China
    Clin Lymphoma Myeloma 7:296-304. 2007
    ..to overcome MM tumor cell resistance and/or sensitize tumor cells to chemotherapeutic treatments currently used, we examined the role of human apurinic/apyrimidinic endonuclease 1 (APE1) in resistance and prognosis in patients with MM.
  40. pmc Human AP endonuclease 1 stimulates multiple-turnover base excision by alkyladenine DNA glycosylase
    Michael R Baldwin
    Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109 0606, USA
    Biochemistry 48:6022-33. 2009
    ..AP endonuclease 1 (APE1) is the predominant enzyme for processing abasic DNA sites in human cells...
  41. doi APE1 Asp148Glu gene polymorphism and lung cancer risk: a meta-analysis
    Ya Nan Ji
    Jiangsu Province Hospital of Traditional Chinese Medicine, 155 Hanzhong Road, 210029 Nanjing, China
    Mol Biol Rep 38:4537-43. 2011
    Many studies have examined the association between the APE1 T1349G (Asp148Glu) gene polymorphisms and lung cancer risk in various populations, but their results have been inconsistent...
  42. ncbi Apurinic/apyrimidinic endonuclease (APE1) gene polymorphisms and lung cancer risk in relation to tobacco smoking
    Bedia Agachan
    Department of Molecular Medicine, Institute for Experimental Medicine DETAE, Faculty of Pharmacy, Istanbul University, CAPA 34390 Istanbul, Turkey
    Anticancer Res 29:2417-20. 2009
    ..Based on this hypothesis, the relationship between APE1 polymorphism, smoking and the risk of lung cancer was explored.
  43. ncbi Association of polymorphisms in base excision repair genes with the risk of breast cancer: a case-control study in North Indian women
    Amit Kumar Mitra
    Genotoxicity Laboratory, Toxicology Division, Central Drug Research Institute, Lucknow, Uttar Pradesh, India
    Oncol Res 17:127-35. 2008
    ..rs1130409/t1865g (apex1), rs1799782/t22142c (xrcc1), rs25487/g23990a (xrcc1), rs4989588/t3337a (fen1), rs4989586/ g3259a (fen1), rs4989587/..
  44. ncbi Association between polymorphisms in the DNA repair genes XRCC1 and APE1, and the risk of prostate cancer in white and black Americans
    Lan Chen
    Division of Cancer Prevention and Control, H Lee Moffitt Cancer Center, Tampa, Florida, USA
    J Urol 175:108-12; discussion 112. 2006
    XRCC1 and APE1 are enzymes involved in the repair of DNA strand breaks and base damage that arise from various endogenous and exogenous oxidants. We determined whether polymorphisms in XRCC1 and APE1 increase the risk of prostate cancer.
  45. doi Association between polymorphisms in DNA base excision repair genes XRCC1, APE1, and ADPRT and differentiated thyroid carcinoma
    Feng Yu Chiang
    Department of Otolaryngology Head and Neck Surgery, Kaohsiung Medical University Hospital, Kaohsiung City, Taiwan
    Clin Cancer Res 14:5919-24. 2008
    DNA BER pathway is related with carcinogenesis. We hypothesized that functional polymorphisms of three BER genes, XRCC1, apurinic/apyrimidinic endonuclease (APE1), and ADPRT, confer risks for DTC and its progression.
  46. pmc Coordinating the initial steps of base excision repair. Apurinic/apyrimidinic endonuclease 1 actively stimulates thymine DNA glycosylase by disrupting the product complex
    Megan E Fitzgerald
    Department of Biochemistry and Molecular Biology, Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA
    J Biol Chem 283:32680-90. 2008
    ..The follow-on base excision repair enzyme, AP endonuclease 1 (APE1), stimulates the turnover of TDG and other glycosylases, involving a mechanism that remains largely unknown...
  47. doi APE1 overexpression is associated with cisplatin resistance in non-small cell lung cancer and targeted inhibition of APE1 enhances the activity of cisplatin in A549 cells
    Dong Wang
    Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China
    Lung Cancer 66:298-304. 2009
    Apurinic/apyrimidinic endonuclease (APE1), a bifunctional AP endonuclease/redox factor, is important in DNA repair and redox signaling, may be associated with chemoresistance...
  48. pmc Redox regulation of DNA repair: implications for human health and cancer therapeutic development
    Meihua Luo
    Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University, Indiana, USA
    Antioxid Redox Signal 12:1247-69. 2010
    ..in the redox regulation of DNA repair is the base excision repair enzyme apurinic/apyrimidinic endonuclease 1 (APE1) in its role as a redox factor...
  49. pmc Human apurinic/apyrimidinic endonuclease (APE1) is a prognostic factor in ovarian, gastro-oesophageal and pancreatico-biliary cancers
    A Al-Attar
    Department of Clinical Oncology, Nottingham University Hospitals NHS Trust, UK
    Br J Cancer 102:704-9. 2010
    ..We investigated whether expression of human AP endonuclease (APE1), a key multifunctional protein involved in DNA BER, would impact on clinicopathological outcomes in ovarian, ..
  50. ncbi Radiation resistance in glioma cells determined by DNA damage repair activity of Ape1/Ref-1
    Mamta D Naidu
    Biology Department, Brookhaven National Laboratory, Upton, NY, USA
    J Radiat Res 51:393-404. 2010
    ..Human apurinic endonuclease 1 (Ape1, Ref-1, APEX, HAP1, AP endo) is a multifunctional protein involved in base excision repair of DNA and a redox-dependent ..
  51. pmc APE1 is the major 3'-phosphoglycolate activity in human cell extracts
    Jason L Parsons
    MRC Radiation and Genome Stability Unit, Harwell, Oxfordshire OX11 0RD, UK
    Nucleic Acids Res 32:3531-6. 2004
    ..the major 3'-PG activity in human WCE is Mg2+ dependent and that this activity co-purifies with AP endonuclease 1 (APE1) over phosphocellulose and gel filtration chromatography...
  52. ncbi A redox factor protein, ref1, is involved in negative gene regulation by extracellular calcium
    T Okazaki
    Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Japan
    J Biol Chem 269:27855-62. 1994
    ..Our Southwestern cloning revealed that a redox factor protein (ref1), which was known to activate several transcription factors via alterations of their redox state, belonged to an ..
  53. pmc Potent inhibition of human apurinic/apyrimidinic endonuclease 1 by arylstibonic acids
    Lauren A Seiple
    The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore MD 21205 2185, USA
    Mol Pharmacol 73:669-77. 2008
    Human apurinic/apyrimidinic endonuclease (Ape1) plays an important role by processing the >10,000 highly toxic abasic sites generated in the genome of each cell every day...
  54. pmc Regulation of the human AP-endonuclease (APE1/Ref-1) expression by the tumor suppressor p53 in response to DNA damage
    Amira Zaky
    Department of Biochemistry and Molecular Biology, Sealy Center for Molecular Medicine, University of Texas Medical Branch, TX 77555, Galveston, USA
    Nucleic Acids Res 36:1555-66. 2008
    The human AP-endonuclease (APE1/Ref-1), an essential multifunctional protein, plays a central role in the repair of oxidative base damage via the DNA base excision repair (BER) pathway...
  55. ncbi The apurinic/apyrimidinic endonuclease activity of Ape1/Ref-1 contributes to human glioma cell resistance to alkylating agents and is elevated by oxidative stress
    John R Silber
    Department of Neurological Surgery, University of Washington, Seattle, Washington 98195, USA
    Clin Cancer Res 8:3008-18. 2002
    Alkylating agents are standard components of adjuvant chemotherapy for gliomas. We provide evidence here that Ape1/Ref-1, the major mammalian apurinic/apyrimidinic endonuclease (Ap endo), contributes to alkylating agent resistance in ..
  56. ncbi Bilirubin-induced cell toxicity involves PTEN activation through an APE1/Ref-1-dependent pathway
    Laura Cesaratto
    Department of Biomedical Sciences and Technologies, University of Udine, 33100, Udine, Italy
    J Mol Med (Berl) 85:1099-112. 2007
    ..The ROS increase activated the antioxidant cell response through APE1/Ref-1, a master redox regulator in eukaryotic cells...
  57. ncbi Human AP endonuclease possesses a significant activity as major 3'-5' exonuclease in human leukemia cells
    Akira Yoshida
    First Department of Internal Medicine, Fukui Medical University, Matsuoka cho, Fukui 910 1193, Japan
    Biochem Biophys Res Commun 310:522-8. 2003
    Apurinic/apyrimidinic (AP) endonuclease (Ape1) is the major cellular enzyme responsible for repairing AP-sites in DNA. It can cleave the DNA phosphodiester backbone immediately 5(') to an AP-site...
  58. doi The DNA repair gene APE1 T1349G polymorphism and cancer risk: a meta-analysis of 27 case-control studies
    Dongying Gu
    Department of Oncology, The Affiliated Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing 210006, People s Republic of China
    Mutagenesis 24:507-12. 2009
    Published data regarding the association between the apurinic/apyrimidinic endonuclease 1 (APE1) T1349G (Asp148Glu) polymorphism and cancer risk show inconclusive results...
  59. doi Genetic polymorphisms of DNA repair genes and chromosomal damage in workers exposed to 1,3-butadiene
    Qi Wang
    Department of Occupational Health and Toxicology, School of Public Health, Fudan University, Key Laboratory of Public Health and Safety of Ministry of Education of China, Shanghai 200032, China
    Carcinogenesis 31:858-63. 2010
    ..cross-complementing group 1 (XRCC1) Arg194Trp, Arg280His, Arg399Gln, T-77C, ADPRT Val762Ala, MGMT Leu84Phe and APE1 Asp148Glu) and chromosomal damage in BD-exposed workers, using the cytokinesis-blocked (CB) micronucleus (MN) assay ..
  60. pmc Identification of RING finger protein 4 (RNF4) as a modulator of DNA demethylation through a functional genomics screen
    Xiaoyi V Hu
    Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 107:15087-92. 2010
    ..Mechanistic studies show that RNF4 interacts with and requires the base excision repair enzymes TDG and APE1 for active demethylation...
  61. ncbi APE/Ref-1 and the mammalian response to genotoxic stress
    Gerhard Fritz
    Division of Applied Toxicology, Institute of Toxicology, University of Mainz, Obere Zahlbacher Str 67, D 55131 Mainz, Germany
    Toxicology 193:67-78. 2003
    ..With respect to transcriptional regulation, both redox dependent and independent mechanisms have been described. APE/Ref-1 also acts as a transcriptional repressor...
  62. ncbi APE1 genotype and risk of bladder cancer: evidence for effect modification by smoking
    Paul D Terry
    Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA
    Int J Cancer 118:3170-3. 2006
    ..b>APE1, the major AP endonuclease of human cells, plays a central role in the repair of AP sites through both its ..
  63. doi A genetic variation in APE1 is associated with gastric cancer survival in a Chinese population
    Qinghong Zhao
    Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
    Cancer Sci 102:1293-7. 2011
    ..We genotyped APE1 rs1760944 by the TaqMan method in 925 gastric cancer patients...
  64. ncbi DNA base-excision repair enzyme apurinic/apyrimidinic endonuclease/redox factor-1 is increased and competent in the brain and spinal cord of individuals with amyotrophic lateral sclerosis
    Arif Y Shaikh
    Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205 2196, USA
    Neuromolecular Med 2:47-60. 2002
    ..with changes in the levels and function of the multifunctional protein apurinic/apyrimidinic endonuclease (APE/Ref-1)...
  65. ncbi Human ribosomal protein S3 interacts with DNA base excision repair proteins hAPE/Ref-1 and hOGG1
    Vijay Hegde
    Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana 70808, USA
    Biochemistry 43:14211-7. 2004
    ..it is shown here that hS3 positively interacts with the human base excision repair (BER) enzymes N-glycosylase/AP lyase OGG1 and APE/Ref-1...
  66. ncbi Apurinic/apyrimidinic endonuclease-1 protein level is associated with the cytotoxicity of L-configuration deoxycytidine analogs (troxacitabine and beta-L-2',3'-dideoxy-2',3'-didehydro-5-fluorocytidine) but not D-configuration deoxycytidine analogs (gemcit
    Wing Lam
    Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA
    Mol Pharmacol 69:1607-14. 2006
    ..We showed that human apurinic/apyrimidinic endonuclease (APE-1) has exonuclease activity for preferentially removing L-OddC and other L-configuration nucleosides over D-..
  67. pmc A prospective study of polymorphisms of DNA repair genes XRCC1, XPD23 and APE/ref-1 and risk of stroke in Linxian, China
    Somdat Mahabir
    Department of Epidemiology, CPB4 3247, UT MD Anderson Cancer Center, Unit 1340, 1155 Pressler Blvd, Houston, TX 77030, USA
    J Epidemiol Community Health 61:737-41. 2007
    ..Stroke is the leading cause of death in Linxian, China. Although there is evidence of DNA damage in experimental stroke, no data exist on DNA repair and stroke in human populations...
  68. doi Nitric oxide initiates progression of human melanoma via a feedback loop mediated by apurinic/apyrimidinic endonuclease-1/redox factor-1, which is inhibited by resveratrol
    Zhen Yang
    Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Orange, California, USA
    Mol Cancer Ther 7:3751-60. 2008
    ..Apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE/Ref-1) is a multifunctional protein and its role in tumor biology has attracted considerable attention...
  69. doi Characterization of nuclear factors modulating the apolipoprotein D promoter during growth arrest: implication of PARP-1, APEX-1 and ERK1/2 catalytic activities
    Louis Charles Levros
    Laboratoire de Biologie Moleculaire, Departement des Sciences Biologiques, and Centre BioMed, Universite du Quebec a Montreal, Montreal, Quebec, Canada
    Biochim Biophys Acta 1803:1062-71. 2010
    ..In this study, we show that Parp-1, HnRNP-U, CBF-A, BUB-3, Kif4, APEX-1 and Ifi204 bind these regulatory elements of the apoD promoter...
  70. ncbi Major oxidative products of cytosine are substrates for the nucleotide incision repair pathway
    Stéphane Daviet
    Groupe Réparation de l ADN, UMR 8126 CNRS, Univ Paris Sud, Institut Gustave Roussy, 94805 Villejuif Cedex, France
    DNA Repair (Amst) 6:8-18. 2007
    ..Here, we characterized the substrate specificity of human major AP endonuclease, Ape1, towards 5-hydroxy-2'-deoxycytidine (5ohC) and alpha-anomeric 2'-deoxycytidine (alphadC) residues...
  71. pmc Nitric oxide controls nuclear export of APE1/Ref-1 through S-nitrosation of cysteines 93 and 310
    Jing Qu
    National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, and Graduate School of the Chinese Academy of Sciences, Beijing, China
    Nucleic Acids Res 35:2522-32. 2007
    Apurinic/apyrimidinic endonuclease 1/redox effector factor-1 (APE1/Ref-1, abbreviated as APE1) is a molecule with dual functions in DNA repair and redox regulation of transcription factors...
  72. pmc Knockdown of the DNA repair and redox signaling protein Ape1/Ref-1 blocks ovarian cancer cell and tumor growth
    Melissa L Fishel
    Department of Pediatrics Section of Hematology Oncology, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    DNA Repair (Amst) 7:177-86. 2008
    Apurinic endonuclease 1/redox effector factor-1 (Ape1/Ref-1 or Ape1) is an essential protein with two distinct functions...
  73. ncbi H(2)O(2) induces translocation of APE/Ref-1 to mitochondria in the Raji B-cell line
    Barbara Frossi
    Immunology Section, Department of Biomedical Sciences and Technologies, University of Udine, Udine, Italy
    J Cell Physiol 193:180-6. 2002
    ..The base excision repair (BER) enzyme APE/Ref-1 normally repairs small nuclear DNA lesion such as oxidized or alkylated bases...
  74. pmc Dual regulation by apurinic/apyrimidinic endonuclease-1 inhibits gastric epithelial cell apoptosis during Helicobacter pylori infection
    Ranajoy Chattopadhyay
    Department of Medicine, University of Virginia, Charlottesville, VA 22908 0708, USA
    Cancer Res 70:2799-808. 2010
    Human apurinic/apyrimidinic endonuclease-1 (APE-1), a key enzyme involved in repair of oxidative DNA base damage, is an important transcriptional coregulator...
  75. pmc A genetic variant in the APE1/Ref-1 gene promoter -141T/G may modulate risk of glioblastoma in a Chinese Han population
    Keke Zhou
    Neurosurgery Department of Huashan Hospital, Fudan University, Shanghai, PR China
    BMC Cancer 11:104. 2011
    The human apurinic/apyrimidinic endonuclease 1/Redox effector factor-1 (APE1/Ref-1) is implicated in tumor development and progression...
  76. pmc Asparagine 212 is essential for abasic site recognition by the human DNA repair endonuclease HAP1
    D G Rothwell
    Imperial Cancer Research Fund Laboratories, University of Oxford, John Radcliffe Hospital, UK
    Nucleic Acids Res 24:4217-21. 1996
    b>HAP1 is a divalent cation-dependent endonuclease from human cells with specificity for apurinic/apyrimidinic (AP) sites in DNA...
  77. ncbi Identification of redox/repair protein Ref-1 as a potent activator of p53
    L Jayaraman
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Genes Dev 11:558-70. 1997
    ..Importantly, we have also determined that Ref-1 can stimulate p53 transactivation in vivo. This is the first example of a noncovalent protein modifier of p53 function identified in cells...
  78. ncbi Huntingtin-associated protein 1 (HAP1) interacts with the p150Glued subunit of dynactin
    S Engelender
    Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Hum Mol Genet 6:2205-12. 1997
    ..We previously identified a protein (HAP1) which binds to huntingtin in a glutamine repeat length-dependent manner...
  79. ncbi Lack of relationship in long-term type 1 diabetic patients between diabetic nephropathy and polymorphisms in apolipoprotein epsilon, lipoprotein lipase and cholesteryl ester transfer protein. Genétique de la Nephropathie Diabétique Study Group. Données Ep
    S Hadjadj
    Medecine B, University Hospital, Angers, France
    Nephrol Dial Transplant 15:1971-6. 2000
    ..Genetic susceptibility contributes to the risk of diabetic nephropathy. Lipid disorders may favour diabetic nephropathy. Thus polymorphisms in lipid metabolism are candidates for the genetic component of risk for diabetic nephropathy...
  80. pmc Human AP-endonuclease 1 and hnRNP-L interact with a nCaRE-like repressor element in the AP-endonuclease 1 promoter
    David T Kuninger
    Department of Human Biological Chemistry and Genetics and Sealy Center for Molecular Science, University of Texas Medical Branch, 6 136 Medical Research Building, Route 1079, Galveston, TX 77555, USA
    Nucleic Acids Res 30:823-9. 2002
    The major human AP-endonuclease 1 (APE1) is a multifunctional protein that plays a central role in the repair of damaged DNA by acting as a dual-function nuclease in the base excision repair pathway...
  81. ncbi Substrate specificity of human endonuclease III (hNTH1). Effect of human APE1 on hNTH1 activity
    Dina R Marenstein
    Department of Pathology and the Kaplan Comprehensive Cancer Center, New York University School of Medicine, New York, New York 10016, USA
    J Biol Chem 278:9005-12. 2003
    ..In contrast to Nth, the DNA N-glycosylase activity of hNTH1 is 7-fold greater than its AP lyase activity when the DNA substrate contains a thymine glycol (Tg) opposite adenine (Tg:A) (Marenstein, D. R...
  82. ncbi CD40 stimulation induces Pax5/BSAP and EBF activation through a APE/Ref-1-dependent redox mechanism
    Sonia Merluzzi
    Dipartimento di Scienze e Tecnologie Biomediche, M A T I Center of Excellence, Piazzale Kolbe 4, Universita Degli Studi di Udine, 33100 Udine, Italy
    J Biol Chem 279:1777-86. 2004
    ..In this study we demonstrate that the redox factor APE/Ref-1 acts as a key signaling intermediate in response to CD40-mediated B cell activation...
  83. ncbi Effects of backbone contacts 3' to the abasic site on the cleavage and the product binding by human apurinic/apyrimidinic endonuclease (APE1)
    Tadahide Izumi
    Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston, Texas 77555 1079, USA
    Biochemistry 43:684-9. 2004
    The mammalian apurinic/apyrimidinic (AP) endonuclease (APE1) is a multifunctional protein that plays essential roles in DNA repair and gene regulation...
  84. ncbi Nucleotide sequence and DNA secondary structure, as well as replication protein A, modulate the single-stranded abasic endonuclease activity of APE1
    Jinshui Fan
    Laboratory of Molecular Gerontology, NIA, National Institutes of Health, Baltimore, MD 21224, USA
    J Biol Chem 281:3889-98. 2006
    A major role of the multifunctional human Ape1 protein is to incise at apurinic/apyrimidinic (AP) sites in DNA via site-specific endonuclease activity...
  85. ncbi Genetic variation in the DNA repair genes is predictive of outcome in lung cancer
    Athena Matakidou
    Section of Cancer Genetics, Institute of Cancer Research, Sutton, UK
    Hum Mol Genet 16:2333-40. 2007
    ..004); ERCC6 G399D (P = 0.023), ERCC6 Q1413R (P = 0.025), POLE (P = 0.014) and base excision repair: APEX1 D148E (P = 0.028); EXO1 E670G (P = 0.007); POLB P242R (P = 0.018)...
  86. doi Aprataxin, poly-ADP ribose polymerase 1 (PARP-1) and apurinic endonuclease 1 (APE1) function together to protect the genome against oxidative damage
    Janelle L Harris
    Queensland Institute of Medical Research, Radiation Biology and Oncology, Brisbane, Queensland 4029, Australia
    Hum Mol Genet 18:4102-17. 2009
    ..Here, we reveal reduced expression of PARP-1, apurinic endonuclease 1 (APE1) and OGG1 in AOA1 cells and demonstrate a requirement for PARP-1 in the recruitment of aprataxin to sites of DNA ..
  87. pmc Redox activation of Fos-Jun DNA binding activity is mediated by a DNA repair enzyme
    S Xanthoudakis
    Department of Molecular Oncology and Virology, Roche Institute of Molecular Biology, New York, NY
    EMBO J 11:3323-35. 1992
    ..This study suggests a novel link between transcription factor regulation, oxidative signalling and DNA repair processes in higher eukaryotes...
  88. pmc Isolation of cDNA clones encoding a human apurinic/apyrimidinic endonuclease that corrects DNA repair and mutagenesis defects in E. coli xth (exonuclease III) mutants
    C N Robson
    Imperial Cancer Research Fund, Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, UK
    Nucleic Acids Res 19:5519-23. 1991
    ..We have isolated cDNA clones which encode an endonuclease, designated HAP1 (human AP endonuclease 1), that catalyses the initial step in AP site repair in human cells...
  89. pmc Activation of apurinic/apyrimidinic endonuclease in human cells by reactive oxygen species and its correlation with their adaptive response to genotoxicity of free radicals
    C V Ramana
    Sealy Center for Molecular Science and Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, TX 77555, USA
    Proc Natl Acad Sci U S A 95:5061-6. 1998
    Apurinic/apyrimidinic (AP) endonuclease (APE; EC 4.2.99...
  90. ncbi Expression and subcellular localization of human AP endonuclease 1 (HAP1/Ref-1) protein: a basis for its role in human disease
    S Kakolyris
    Department of Cellular Science, John Radcliffe Hospital, University of Oxford
    Histopathology 33:561-9. 1998
    Human AP endonuclease 1 (HAP1) plays a major role in the repair of apurinic/apyrimidinic (AP) sites in cellular DNA by catalysing hydrolytic cleavage of the phosphodiester backbone 5' to the site...
  91. ncbi Phosphorylation of the DNA repair protein APE/REF-1 by CKII affects redox regulation of AP-1
    G Fritz
    Division of Applied Toxicology, Institute of Toxicology, University of Mainz, Germany
    Oncogene 18:1033-40. 1999
    The DNA repair protein apurinic endonuclease (APE/Ref-1) exerts several physiological functions such as cleavage of apurinic/apyrimidinic sites and redox regulation of the transcription factor AP-1, whose activation is part of the ..
  92. ncbi Abasic site recognition by two apurinic/apyrimidinic endonuclease families in DNA base excision repair: the 3' ends justify the means
    C D Mol
    Department of Molecular Biology, and Skaggs Institute for Chemical Biology, The Scripps Research Institute, MB4, 10550 North Torrey Pines Road, La Jolla, CA 92037 1027, USA
    Mutat Res 460:211-29. 2000
    ..In humans, AP sites are processed by APE1, whereas in yeast the primary AP endonuclease is termed APN1, and these enzymes are the major constitutively ..
  93. ncbi Determinants in nuclease specificity of Ape1 and Ape2, human homologues of Escherichia coli exonuclease III
    Masood Z Hadi
    Molecular and Structural Biology Division, Lawrence Livermore National Laboratory, Livermore, CA 94551, USA
    J Mol Biol 316:853-66. 2002
    ..b>Ape1, which shares homology with Escherichia coli exonuclease III (ExoIII), is the major abasic endonuclease in mammals ..
  94. ncbi AP endonuclease 1 coordinates flap endonuclease 1 and DNA ligase I activity in long patch base excision repair
    Tamara A Ranalli
    Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York, 14642
    J Biol Chem 277:41715-24. 2002
    ..Apurinic/apyrimidinic (AP) endonucleases recognize and cleave abasic (AP) sites during base excision repair (BER). APE1 (REF1, HAP1) is the predominant AP endonuclease in mammalian cells...
  95. ncbi AP endonuclease 1 has no biologically significant 3(')-->5(')-exonuclease activity
    Natalia A Lebedeva
    Novosibirsk Institute of Bioorganic Chemistry, Siberian Division of Russian Academy of Sciences, Prospect Lavrentiev 8, 630090, Novosibirsk, Siberia, Russia
    Biochem Biophys Res Commun 300:182-7. 2003
    The 3(')-->5(')-exonucleolytic activity of human apurinic/apyrimidinic endonuclease 1 (APE1) on mispaired DNA at the 3(')-termini of recessed, nicked or gapped DNA molecules was analyzed and compared with the primary endonucleolytic ..
  96. ncbi Implication of Ref-1 in the repression of renin gene transcription by intracellular calcium
    Sebastien Fuchs
    INSERM U36, College de France, Paris, France
    J Hypertens 21:327-35. 2003
    ..As the renin gene is negatively regulated by calcium in the same way as the parathormone (PTH) gene, we hypothesized that a similar molecular transcriptional mechanism could be involved...
  97. ncbi Modulation of the 3'-->5'-exonuclease activity of human apurinic endonuclease (Ape1) by its 5'-incised Abasic DNA product
    Donny Wong
    Department of Cancer Cell Biology, Harvard School of Public Health, Boston, Massachusetts 02115, USA
    J Biol Chem 278:36242-9. 2003
    The major abasic endonuclease of human cells, Ape1 protein, is a multifunctional enzyme with critical roles in base excision repair (BER) of DNA...
  98. ncbi Studies of apurinic/apyrimidinic endonuclease/ref-1 expression in epithelial ovarian cancer: correlations with tumor progression and platinum resistance
    Sarah Freitas
    Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
    Clin Cancer Res 9:4689-94. 2003
    ..repair pathway involves the cleavage of an apurinic/apyrimidinic site by an apurinic/apyrimidinic endonuclease (APE)...
  99. pmc Role of acetylated human AP-endonuclease (APE1/Ref-1) in regulation of the parathyroid hormone gene
    Kishor K Bhakat
    Sealy Center for Molecular Science and Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, TX 77555 1079, USA
    EMBO J 22:6299-309. 2003
    The human AP-endonuclease (APE1/Ref-1), a multifunctional protein central to repairing abasic sites and single-strand breaks in DNA, also plays a role in transcriptional regulation...
  100. ncbi Helicobacter pylori and H2O2 increase AP endonuclease-1/redox factor-1 expression in human gastric epithelial cells
    Song Ze Ding
    Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, USA
    Gastroenterology 127:845-58. 2004
    ..Apurinic/apyrimidinic endonuclease-1 (APE-1)/redox factor-1 (Ref-1) repairs damaged DNA and reductively activates transcription factors, including activator ..
  101. ncbi Apurinic/apyrimidinic endonuclease 1 regulates endothelial NO production and vascular tone
    Byeong Hwa Jeon
    Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21214, USA
    Circ Res 95:902-10. 2004
    The dual-function protein apurinic/apyrimidinic endonuclease/redox factor-1 (APE1/ref-1) is essential for DNA repair and also governs the reductive activation of many redox-sensitive transcription factors...

Research Grants69

  1. Cardioscopy New Platform for Less Invasive Surgery on the Beating Heart
    Tomislav Mihaljevic; Fiscal Year: 2013
    ..The Cardioscope will be placed near the LV apex via a small thoracotomy or small subxiphoid incision or across the aortic valve via the carotid or femoral artery ..
  2. Intravascular Cardiac Assist System for Decompression and Recovery
    CAITLYN J BOSECKER; Fiscal Year: 2010
    ..e. as an LVAD), where blood is withdrawn from either the left atrium or the apex of the left ventricle. The blood then passes through the pump and is returned to the ascending aorta...
  3. ALAN BRENT PACKARD; Fiscal Year: 2014
    ..high accumulation in the heart, minimal accumulation in the liver (which can interfere with visualization of the apex of the left ventricle), and rapid blood clearance...
  4. Daniel Tamez; Fiscal Year: 2014
    ..trials, the tMVAD is significantly smaller in size and weight and only requires a single insertion through the apex of the left ventricle...
  5. Myosin Isoforms in Relation to Function in Human Heart
    Richard L Moss; Fiscal Year: 2010
    ..varies with MHC content will be investigated by determining the regional distribution of MHC isoforms in the apex and the left ventricular free wall from healthy and diseased hearts...
  6. Development of an Implantable "Plug and Play" TransApical to Aorta VAD
    Stephen Topaz; Fiscal Year: 2007
    ..a blood return graft (or cannula) to the aorta and a large cannula (>16 mm outer diameter) through the cardiac apex. Our goal is to develop a Plug and Play (P&P) TransApical to Aorta VAD pump that is simple and easily inserted ..
  7. Molecular Epidemiology and Natural History of SIVcpz
    Beatrice H Hahn; Fiscal Year: 2013
    ..based) SIVcpz detection methods and used these to characterize the molecular epidemiology of SIVcpz in wild-living ape populations throughout equatorial Africa (Nature 2004;Science 2006)...
  8. Regulations of DNA Alkylation/Deamination Damage Repair
    Rabindra Roy; Fiscal Year: 2013
    ..However, MPG lacking its N-terminal extension is stimulated by APE. Thus, these novel preliminary observations provide the ground work to test our central hypothesis that the dynamic ..
  9. Kishor K Bhakat; Fiscal Year: 2015
    ..The mammalian AP-endonuclease (APE1) plays a central role in the BER pathway by repairing abasic (AP) sites generated in DNA spontaneously or after ..
  10. Role of ROS-Induced DNA Damage in Mitochondria-Regulated Apoptosis
    Anne Tann; Fiscal Year: 2012
    ..APE1 also functions as redox factor 1 due to its ability to reductively activate transcription factors, such as c-Jun and p53...
  11. Repair of oxidative DNA damage in mammalian cells
    Tadahide Izumi; Fiscal Year: 2013
    ..Apurinic/apyrimidinic endonuclease (APE1 in mammals) arguably determines the BER rate in cells and thus plays a central role in the repair pathway...
  12. Beatrice H Hahn; Fiscal Year: 2016
    ..Screening ape samples from over 50 field sites throughout central Africa, we found that P...
  13. Beatrice H Hahn; Fiscal Year: 2016
    ..Specifically, we propose: 1. To identify the ape reservoirs of HIV-1 groups O and P...
  14. Sheila E Crowe; Fiscal Year: 2015
    ..This project has focused on ROS-induced activation of apurinic/apyrimidinic endonuclease (APE1), a multifunctional protein that is the rate-limiting enzyme in DNA base excision repair of oxidative lesions...
  15. Interaction Between DNA Repair and Antioxidant Genes During Aging
    Carlos A Torres Ramos; Fiscal Year: 2010
    ..the yeast Saccharomyces cerevisiae, and a more complex mammalian organism, a knockout mouse heterozygous for Ape1, the main AP endonuclease that participates in BER...
  16. Jun Chen; Fiscal Year: 2016
    ..AP endonuclease (APE) is the rate-limiting enzyme in the BER pathway, which, when overexpressed, can boost BER activity...
  17. Oxidative Stress, Mitochondrial Dysfunction and Aging
    JOHN NMN PAPACONSTANTINOU; Fiscal Year: 2010
    ..P2 (SM) investigates how aging affects the role of APE1 in nuclear and mtDNA repair;the role of the negative Ca++ response element (nCaRE) in regulation of expression of ..
  18. ALEX C DROHAT; Fiscal Year: 2016
    ..Repair continues with AP endonuclease (APE1) and downstream BER enzymes...
  19. The Role of Ape1 in Neurotoxicity of Cancer Treatments
    Mark R Kelley; Fiscal Year: 2012
    ..The DNA base excision repair (BER) pathway including the abasic- endonuclease1/redox factor (Ape1/Ref-1 or Ape1) has been shown to be the major DNA repair pathway for oxidative and alkylating agent damage that ..
  20. STRUCTURE AND FUNCTION OF DNA REGULATORY PROTEINS
    Ronen Marmorstein; Fiscal Year: 2010
    ..We have previously determined the structures of DNA complexes with the Gal4, Ppr1, Put3, Hap1 and Leu3 members of this family...
  21. DAVID K CORTEZ; Fiscal Year: 2016
    ..The ATR (ATM and rad3-related) kinase functions at the apex of a DNA damage and replication stress response pathway...
  22. Mechanisms of Trinucleotide Repeat Expansion via Oxidative DNA Damage and Repair
    Yuan Liu; Fiscal Year: 2012
    ..can be reduced by efficient processing of ssDNA break intermediates through BER protein interactions between APE1 and Pol p, XRCC1 and Pol 3, as well as BLM and FEN1. Under Dr...
  23. Tumor suppressor adenomatous polyposis coli and breast carcinogenesis
    Satya Narayan; Fiscal Year: 2007
    ..excision repair proteins, including proliferating cell nuclear antigen (PCNA) and apurinic/apydmidinic endonudease (APE)...
  24. ANN NARDULLI; Fiscal Year: 2014
    ..thioredoxin (Trx), thioredoxin reductase (TrxR), protein disulfide isomerase (PDI), and apurinic endonuclease 1 (APE1) in the cerebral cortex of C57BL/6 mice, (2) define whether estrogens and/or progestins alter the expression of ..
  25. Innate Immunity, Biomarkers and Myocardial Infarction
    Gregory L Stahl; Fiscal Year: 2010
    ..While recent clinical trials (e.g., APEX-MI and COMPLY) did not reach statistical significance for the primary endpoint, ended early because of the failed ..
  26. Dissecting the role of one neuronal RhoGEF amongst many: the Kalirin-7 null mouse
    Richard E Mains; Fiscal Year: 2012
    ..In addition, Kalirin interacts with DISC1 (a candidate schizophrenia gene) and HAP1 (a Huntingtin interactor)...
  27. Taras Y Nazarko; Fiscal Year: 2014
    ..and another protein we identified as Atg36, are essential for selective autophagy of peroxisomes (pexophagy) and Ape1 complexes (Cvt pathway) in the Pichia pastoris yeast...
  28. TH1 AND TH2 RESPONSES IN VIRAL IMMUNITY
    Thomas M Moran; Fiscal Year: 2010
    ..inflammatory response in the animals until almost 48 hours after infection when virus replication was reaching its apex. At this point, a sudden rapid generation of chemokines and cytokines that we refer to as the inflammatory burst ..
  29. NEUROSECRETORY GENE EXPRESSION IN THE HYPOTHALAMUS
    Pamela L Mellon; Fiscal Year: 2011
    As the ultimate regulator of reproductive function, Gonadotropin-releasing hormone (GnRH) is at the apex of the hypothalamic-pituitary-gonadal axis...
  30. Role of an RNA-Binding Protein in Mammary Carcinogenesis
    Jeffrey Ross; Fiscal Year: 2009
    ..The goal is to assess how the tumor suppressor Ape and the chemical carcinogen N-ethyl-N-nitrosurea (ENU) affect CRD-BP-mediated tumor formation...
  31. Soy isoflavones to augment radiotherapy of lung carcinoma
    Gilda G Hillman; Fiscal Year: 2012
    ..and modulation of molecular pathways involved in the interaction between radiation and soy isoflavones, including APE1/Ref-1, NF-:B, HIF-11...
  32. Factors that Initiate Arrhythamias in Long QT Syndrome
    Guy Salama; Fiscal Year: 2006
    ..We will apply a focal sensory stimulus (mechanical or chemical) at a site on the heart (i.e. the apex of the left ventricle) while recording changes in electrical and contractile parameters mediated by cardiac reflex ..
  33. HEME PROTEIN REDUCTASES
    Stephen G Sligar; Fiscal Year: 2012
    ..step in androgen formation via the cleavage of the C17-C20 bond to generate the characteristic keto group at the apex of the D-ring in androgens and the reaction catalyzed by the important drug target, aromatase, wherein an aromatic ..
  34. Hajime Sasaki; Fiscal Year: 2014
    ..inflammation within the jaws that ultimately results in the destruction of bone that surrounds the apex of the tooth root...
  35. Genome wide views of chromatin occupancy in the control of Aquilegia development
    Levi Yant; Fiscal Year: 2013
    ..flowering time, plants interpret a variety of signals that converge from multiple genetic pathways at the shoot apex where the reproductive transition is effected2,3...
  36. Adverse Effects of Noise on Hearing: Basic Mechanisms
    Barbara A Bohne; Fiscal Year: 2010
    ..e., 4-kHz octave band of noise (OBN) or 0.5-kHz OBN at 92-95 dB SPLJ. With Specific Aim #1, the apex-to-base patterns and types of cell death and their timing will be determined in hair cells at 0, 7, 14 and 30 days ..
  37. A shared macromolecular X-ray diffraction system in Rochester
    Joseph E Wedekind; Fiscal Year: 2010
    ..stages, our tests indicated that the Bruker AXS I?S microfocus sealed tube X- ray source, integrated optics, APEX II CCD detector, Oxford 700 cold stream and motorized goniometer head (for rapid sample centering) mounted on a 4-..
  38. Dissecting Wnt/PCP Signaling in Developing Cochlear Sensory Epithelium
    Xiaowei Lu; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): The actin-based stereocilary bundle (or hair bundle) on the apex of auditory hair cells serves the crucial function of converting sound energy to electric signals...
  39. Anilkumar Pillai; Fiscal Year: 2016
    ..We found reductions in TrkB signaling, Hap1 (a huntingtin associated protein involved in intracellular trafficking of endocytic TrkB) levels and its ..
  40. Ian G Macara; Fiscal Year: 2015
    ..Par3 sits at the apex of a signaling network that controls cell polarity, and we discovered two crucial downstream functions of Par3 in ..
  41. A novel mouse colon cancer model and chemoprevention
    Wei Dai; Fiscal Year: 2010
    ..Given that both BubRl and Ape are involved in the regulation of genomic stability in normal cells, we hypothesize that BubRl+/-ApcMin+/- mice ..
  42. Effects of High Fat Diet and Environmental Obesogen Co-Exposure on Osteoporosis
    Jennifer J Schlezinger; Fiscal Year: 2013
    ..Since PPAR? is poised at the apex of a regulatory network that controls multi-potent marrow stem cell (MSC) differentiation, it is posited that ..
  43. KUMBLE SANDEEP PRABHU; Fiscal Year: 2016
    ..However, studies are yet to be done to understand the effect of Se on cancer stem cells (CSC), which occupy the apex of the developmental hierarchy with properties of self-renewal, multipotentiality, and strong proliferative ..
  44. Progranulin Intervention in Inflammatory Bowel Diseases
    Chuanju Liu; Fiscal Year: 2013
    ..these cytokines, tumor necrosis factor (TNF) has received the greatest attention because of its position at the apex of the inflammatory and immune-regulatory cascades...
  45. Anxiety and Alcohol Drinking in a Genetic Animal Model of Alcoholism
    JULIA ANN CHESTER; Fiscal Year: 2010
    ..and innate propensity toward alcohol drinking behavior in mouse lines that have been selectively bred for high (HAP1 and HAP2) or low (LAP1 and LAP2) alcohol preference...
  46. Functions and Disorders of K Channels in the Ineer Ear
    Tsung Yu Chen; Fiscal Year: 2012
    ..expression of different isoforms/alternative splice variants is the underlying mechanisms for the base-to-apex PHL seen in mutations of KCNQ4 channels...
  47. William G Dunphy; Fiscal Year: 2016
    ..In vertebrates, the master regulatory kinase ATR functions at the apex of key checkpoint responses...
  48. Celine DerMardirossian; Fiscal Year: 2016
    ..We hypothesize that nephrin is at the apex of a hierarchy defining compartment identity through the recruitment of GTPases and their regulators...
  49. RICHARD LOWELL BELL; Fiscal Year: 2014
    ..nt is to supply to off-campus researchers at cost P/NP, HAD1-2/LAD1-2, and AA/ANA selectively bred rats, as well as HAP1-2-3/LAP2-3 and cHAP selected mice that show genetically high and/or low alcohol preference. (Specific Aims 2 and 3)...
  50. CHARLES RICHARD STEELE; Fiscal Year: 2016
    ..detailed 3D description of the Y- shaped elements in the organ of Corti across the different OHC rows, from base to apex;2) an incorporation of this information into computational models for testing the FF/FB amplifier theories with ..
  51. Early Detection of Keratoconus
    Ronald H Silverman; Fiscal Year: 2013
    ..In early keratoconus, as the anterior stromal surface begins to bulge forward, the epithelium will thin above the apex of the bulge and thicken around it, to maintain a smooth anterior surface...
  52. NICOLAS P SLUIS-CREMER; Fiscal Year: 2016
    ..screened, we identified 3,39-[(3-carboxy-4-oxo-2,5-cyclohexadien-1- ylidene)methylene]bis[6-hydroxy-benzoic acid] (APEX-57219) as a promising "lead" compound...
  53. Roberto N De Guzman; Fiscal Year: 2016
    ..assembly consists of about 120 copies of identical proteins that are arranged in a superhelical manner, and the apex of this needle is capped by tip proteins...
  54. The Effect of Dietary Fat on Benzo(a)pyrene Induced Colon Cancer in Apc Min Mice
    DEACQUNITA LAQUADE DIGGS; Fiscal Year: 2010
    ..aims: Aim 1: To investigate the effect of dietary fat on BaP-induced adenomas in colon and rectum of the adult Ape Min mouse...
  55. Mitigating risk in a closed loop system by exercise detection and miniaturization
    Peter G Jacobs; Fiscal Year: 2013
    ..AP system as well as results from simulations will guide the design of an Adaptive Personalized Exercise-sensing (APE) algorithm...
  56. Kalyanam Shivkumar; Fiscal Year: 2016
    ..control of myocardial excitability in normal and diseased human hearts, and specifically, regional differences (apex versus base, epicardium versus endocardium, right versus left stellate ganglion innervation) remain unknown and ..
  57. Determinants of Pathogenic Hantavirus Attachment
    Erich R Mackow; Fiscal Year: 2010
    ..Pathogenic hantaviruses bind to a 53 residue PSI domain present at the apex of bent, inactive, 1v23 integrins and dysregulate 1v23 integrin function (33, 73)...
  58. Ming Zhao; Fiscal Year: 2014
    ..Second, these vascular regions are also the primary targets for anti-PE (aPE) autoimmunity, providing a physical link between aPE and idiopathic thrombosis...
  59. Chuanju Liu; Fiscal Year: 2015
    ..by applicant): Tumor necrosis factor-a (TNF?) has received the greatest attention because of its position at the apex of the pro-inflammatory cytokine cascade, and its dominance in the pathogenesis of inflammation...
  60. KUMBLE SANDEEP PRABHU; Fiscal Year: 2015
    ..LSCs reside at the apex of a developmental hierarchy and facilitate the continued expansion of bulk tumor cells leading to relapse of the ..
  61. Pharmaceutical Therapy for Seasonal Affective Disorder
    Jay K Trautman; Fiscal Year: 2010
    ..The pathway has at its apex, melanopsin, a G-protein coupled receptor (GPCR) that is only expressed in the target cells...
  62. Zhenbiao Yang; Fiscal Year: 2015
    ..growth requires efficient and targeted fusion of vesicles (containing cell membrane and wall materials) to the cell apex. This targeted exocytosis is highly coordinated in space and time and is orchestrated by a Rho GTPase-based ..
  63. DNA repair and lg class switching
    Janet Stavnezer; Fiscal Year: 2007
    ..Aim 2: to determine if the base excision repair (BER) enzymes APE1 or APE2 create the initiating DNA breaks in the Su segments...
  64. REGENERATION OF PULP-DENTIN DEVELOPMENT IN IMMATURE PERMANENT TEETH WITH NECROSIS
    Kenneth M Hargreaves; Fiscal Year: 2010
    ..method of treating these cases is apexification (formation/induction of a calcified barrier across the root apex), which leaves a greatly weakened tooth with a poor long term prognosis...
  65. HUMAN DNA REPAIR ENZYMES FOR REDOX AND ALKYLATION DAMAGE
    BRUCE F DEMPLE; Fiscal Year: 2010
    ..remove altered bases to generate abasic sites, which are further processed in several steps dependent on the Ape1 endonuclease and DNA polymerase beta...
  66. METALLOENZYME SYNTHESIS, STRUCTURE AND FUNCTION
    William Konigsberg; Fiscal Year: 1999
    ..under investigation are: 1) alkaline phosphatase; 2) the fungal transcription factors GAL4, LAC9, MAL63, LEU3 and HAP1; 3) the glucocorticoid and estrogen receptors from the hormone receptor class of zinc transcription factors; and 4) ..
  67. HORMONE PULSATILITY DIFFERENCES VIA COARSE TIME-SAMPLING
    Steven Pincus; Fiscal Year: 2001
    ..differentiate hormonal secretory patterns between clinically distinct cohorts, via Approximate entropy (ApEn) and cross-ApEn, quantifications of sequential irregularity and two-variable asynchrony, respectively, developed by ..
  68. BioPulp: Bioengineeering approaches for dental pulp regeneration
    SUSAN FU; Fiscal Year: 2009
    ..In deciduous teeth or young permanent teeth with incomplete root apex formation, endodontic treatment is either contra-indicated or may lead to the cessation of root development...
  69. Development of Translation Initiation Inhibitors and their Anti-Cancer Activity
    Michael Chorev; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): The location of translation initiation at the apex of many well-defined oncogenic, pro-apoptotic and tumor-suppressor pathways makes it an attractive target for the development of anti-cancer agents ..