Transcriptional regulatory functions of mammalian AP-endonuclease (APE1/Ref-1), an essential multifunctional protein.

The mammalian AP-endonuclease (APE1/Ref-1) plays a central role in the repair of oxidized and alkylated bases in mammalian genomes via the base excision repair (BER) pathway. However, APE1, unlike its E. coli prototype Xth, has two unique and apparently distinct transcriptional regulatory activities. APE1 functions as a redox effector factor (Ref-1) for several transcription factors including AP-1, HIF1-alpha, and p53. APE1 was also identified as a direct trans-acting factor for repressing human parathyroid hormone (PTH) and renin genes by binding to the negative calcium-response element (nCaRE) in their promoters. We have characterized APE1's post-translational modification, namely, acetylation which modulates its transcriptional regulatory function. Furthermore, stable interaction of APE1 with several other trans-acting factors including HIF-1alpha, STAT3, YB-1, HDAC1, and CBP/p300 and formation of distinct trans-acting complexes support APE1's direct regulatory function for diverse genes. Multiple functions of mammalian APE1, both in DNA repair and gene regulation, warrant extensive analysis of its own regulation and dissection of the mechanisms. In this review, we have discussed APE1's own regulation and its role as a transcriptional coactivator or corepressor by both redox-dependent and redox-independent (acetylation-mediated) mechanisms, and explore the potential utility of targeting these functions for enhancing drug sensitivity of cancer cells.

[1]  H. Izumi,et al.  Increased nuclear localization of transcription factor Y-box binding protein 1 accompanied by up-regulation of P-glycoprotein in breast cancer pretreated with paclitaxel. , 2009, Clinical cancer research : an official journal of the American Association for Cancer Research.

[2]  M. Georgiadis,et al.  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. , 2008, Antioxidants & redox signaling.

[3]  K. Ando,et al.  A new APE1/Ref-1-dependent pathway leading to reduction of NF-κB and AP-1, and activation of their DNA-binding activity , 2008, Nucleic acids research.

[4]  W. Braun,et al.  Unusual role of a cysteine residue in substrate binding and activity of human AP-endonuclease 1. , 2008, Journal of molecular biology.

[5]  Y. Yoo,et al.  Redox factor‐1 mediates NF‐κB nuclear translocation for LPS‐induced iNOS expression in murine macrophage cell line RAW 264.7 , 2008, Immunology.

[6]  Fengqin Gao,et al.  Bcl2 Inhibits Abasic Site Repair by Down-regulating APE1 Endonuclease Activity* , 2008, Journal of Biological Chemistry.

[7]  G. Hutchins,et al.  Knockdown of the DNA repair and redox signaling protein Ape1/Ref-1 blocks ovarian cancer cell and tumor growth. , 2008, DNA repair.

[8]  K. Bhakat,et al.  Regulation of the human AP-endonuclease (APE1/Ref-1) expression by the tumor suppressor p53 in response to DNA damage , 2008, Nucleic acids research.

[9]  S. Gustincich,et al.  APE1/Ref-1 regulates PTEN expression mediated by Egr-1 , 2008, Free radical research.

[10]  B. Demple,et al.  ATF4-Dependent Oxidative Induction of the DNA Repair Enzyme Ape1 Counteracts Arsenite Cytotoxicity and Suppresses Arsenite-Mediated Mutagenesis , 2007, Molecular and Cellular Biology.

[11]  Jide Wang,et al.  Helicobacter pylori Infection Induces Oxidative Stress and Programmed Cell Death in Human Gastric Epithelial Cells , 2007, Infection and Immunity.

[12]  M. Kelley,et al.  The DNA base excision repair protein Ape1/Ref-1 as a therapeutic and chemopreventive target. , 2007, Molecular aspects of medicine.

[13]  J. Qu,et al.  Nitric oxide controls nuclear export of APE1/Ref-1 through S-nitrosation of Cysteines 93 and 310 , 2007, Nucleic acids research.

[14]  M. Yoder,et al.  Ape1 regulates hematopoietic differentiation of embryonic stem cells through its redox functional domain. , 2007, Blood.

[15]  H. Zhang,et al.  Down-regulation of apurinic/apyrimidinic endonuclease 1/redox factor-1 expression by soy isoflavones enhances prostate cancer radiotherapy in vitro and in vivo. , 2007, Cancer research.

[16]  N. Gorbunov,et al.  Spatial coordination of cell-adhesion molecules and redox cycling of iron in the microvascular inflammatory response to pulmonary injury. , 2007, Antioxidants & redox signaling.

[17]  S. Mitra,et al.  Interleukin-8 Induction by Helicobacter pylori in Gastric Epithelial Cells is Dependent on Apurinic/Apyrimidinic Endonuclease-1/Redox Factor-11 , 2006, The Journal of Immunology.

[18]  S. Mitra,et al.  Identification and characterization of mitochondrial abasic (AP)-endonuclease in mammalian cells , 2006, Nucleic acids research.

[19]  K. Bhakat,et al.  Acetylation of Human 8-Oxoguanine-DNA Glycosylase by p300 and Its Role in 8-Oxoguanine Repair In Vivo , 2006, Molecular and Cellular Biology.

[20]  Cuk-Seong Kim,et al.  Apurinic/apyrimidinic endonuclease1/redox factor-1 inhibits monocyte adhesion in endothelial cells. , 2006, Cardiovascular research.

[21]  D. Mercola,et al.  The transcription factor Egr1 is a direct regulator of multiple tumor suppressors including TGFβ1, PTEN, p53, and fibronectin , 2006, Cancer Gene Therapy.

[22]  E. Seto,et al.  Acetylation and deacetylation of non-histone proteins. , 2005, Gene.

[23]  L. Poole,et al.  Synthesis of chemical probes to map sulfenic acid modifications on proteins. , 2005, Bioconjugate chemistry.

[24]  M. Berger,et al.  Apurinic/Apyrimidinic Endonuclease Activity Is Associated with Response to Radiation and Chemotherapy in Medulloblastoma and Primitive Neuroectodermal Tumors , 2005, Clinical Cancer Research.

[25]  M. Gulisano,et al.  Activation of APE1/Ref-1 is dependent on reactive oxygen species generated after purinergic receptor stimulation by ATP , 2005, Nucleic acids research.

[26]  S. Snyder,et al.  S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding , 2005, Nature Cell Biology.

[27]  C. Theriot,et al.  Analysis of nuclear transport signals in the human apurinic/apyrimidinic endonuclease (APE1/Ref1) , 2005, Nucleic acids research.

[28]  N. Tonks.  Redox Redux: Revisiting PTPs and the Control of Cell Signaling , 2005, Cell.

[29]  S. Schreiber,et al.  Induction of DNA repair proteins, Ref-1 and XRCC1, in adult rat brain following kainic acid-induced seizures , 2005, Brain Research.

[30]  Jinshui Fan,et al.  Protein-protein interactions and posttranslational modifications in mammalian base excision repair. , 2005, Free radical biology & medicine.

[31]  L. Ellis,et al.  HIF-1α, STAT3, CBP/p300 and Ref-1/APE are components of a transcriptional complex that regulates Src-dependent hypoxia-induced expression of VEGF in pancreatic and prostate carcinomas , 2005, Oncogene.

[32]  David J. Chen,et al.  Two essential but distinct functions of the mammalian abasic endonuclease. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[33]  M. Kelley,et al.  The multifunctional DNA repair/redox enzyme Ape1/Ref-1 promotes survival of neurons after oxidative stress. , 2005, DNA repair.

[34]  G. Tell,et al.  Cross-regulation between Egr-1 and APE/Ref-1 during early response to oxidative stress in the human osteoblastic HOBIT cell line: Evidence for an autoregulatory loop , 2005, Free radical research.

[35]  W. Deppert,et al.  Redox factor 1 (Ref-1) enhances specific DNA binding of p53 by promoting p53 tetramerization , 2005, Oncogene.

[36]  G. Tell,et al.  The intracellular localization of APE1/Ref-1: more than a passive phenomenon? , 2005, Antioxidants & redox signaling.

[37]  B. Demple,et al.  A vital role for Ape1/Ref1 protein in repairing spontaneous DNA damage in human cells. , 2005, Molecular cell.

[38]  J. den Hertog,et al.  Redox regulation of protein-tyrosine phosphatases. , 2005, Archives of biochemistry and biophysics.

[39]  B. Jeon,et al.  Apurinic/Apyrmidinic Endonuclease 1 Regulates Endothelial NO Production and Vascular Tone , 2004, Circulation research.

[40]  T. Denning,et al.  Helicobacter pylori and H2O2 increase AP endonuclease-1/redox factor-1 expression in human gastric epithelial cells. , 2004, Gastroenterology.

[41]  D. Hedley,et al.  Effects of gemcitabine on APE/ref-1 endonuclease activity in pancreatic cancer cells, and the therapeutic potential of antisense oligonucleotides , 2004, British Journal of Cancer.

[42]  Samuel H. Wilson,et al.  AP endonuclease-independent DNA base excision repair in human cells. , 2004, Molecular cell.

[43]  G. Wilson,et al.  Ref‐1/Ape is critical for formation of the hypoxia‐inducible transcriptional complex on the hypoxic response element of the rat pulmonary artery endothelial cell VEGF gene , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[44]  Dong Wang,et al.  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. , 2004, Molecular cancer therapeutics.

[45]  K. Bhakat,et al.  Acetylation of the human DNA glycosylase NEIL2 and inhibition of its activity. , 2004, Nucleic acids research.

[46]  C. Raut,et al.  Direct effects of recombinant human endostatin on tumor cell IL-8 production are associated with increased endothelial cell apoptosis in an orthotopic model of human pancreatic cancer , 2004, Cancer biology & therapy.

[47]  P. Karplus,et al.  Protein sulfenic acids in redox signaling. , 2004, Annual review of pharmacology and toxicology.

[48]  M. Sigvardsson,et al.  CD40 Stimulation Induces Pax5/BSAP and EBF Activation through a APE/Ref-1-dependent Redox Mechanism* , 2004, Journal of Biological Chemistry.

[49]  K. Bhakat,et al.  Role of acetylated human AP‐endonuclease (APE1/Ref‐1) in regulation of the parathyroid hormone gene , 2003, The EMBO journal.

[50]  M. Tomicic,et al.  APE/Ref-1 and the mammalian response to genotoxic stress. , 2003, Toxicology.

[51]  A. Jaiswal,et al.  Mammalian DNA base excision repair proteins: their interactions and role in repair of oxidative DNA damage. , 2003, Toxicology.

[52]  L. Hansen,et al.  Is DNA repair compromised in Alzheimer’s disease? , 2003, Neurobiology of Aging.

[53]  S. Akira,et al.  Stat3 protects against Fas-induced liver injury by redox-dependent and -independent mechanisms. , 2003, The Journal of clinical investigation.

[54]  H. Izumi,et al.  The pleiotropic functions of the Y-box-binding protein, YB-1. , 2003, BioEssays : news and reviews in molecular, cellular and developmental biology.

[55]  T. Curran,et al.  Cysteine 64 of Ref-1 Is Not Essential for Redox Regulation of AP-1 DNA Binding , 2003, Molecular and Cellular Biology.

[56]  F. Pinet,et al.  Implication of Ref-1 in the repression of renin gene transcription by intracellular calcium , 2003, Journal of hypertension.

[57]  S. Mitra,et al.  The discovery of a new family of mammalian enzymes for repair of oxidatively damaged DNA, and its physiological implications. , 2003, Carcinogenesis.

[58]  Moon-Kyoung Bae,et al.  Regulation and Destabilization of HIF-1α by ARD1-Mediated Acetylation , 2002, Cell.

[59]  K. Kataoka,et al.  Spatial Redox Regulation of a Critical Cysteine Residue of NF-κB in Vivo * , 2002, The Journal of Biological Chemistry.

[60]  Y. Seo,et al.  Selenomethionine regulation of p53 by a ref1-dependent redox mechanism , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[61]  H. Seo,et al.  Oxidoreductive modification of two cysteine residues in paired domain by Ref-1 regulates DNA-binding activity of Pax-8. , 2002, Biochemical and biophysical research communications.

[62]  Ulf Hellman,et al.  Control of Smad7 stability by competition between acetylation and ubiquitination. , 2002, Molecular cell.

[63]  S. Mitra,et al.  Identification and Characterization of a Novel Human DNA Glycosylase for Repair of Cytosine-derived Lesions* , 2002, The Journal of Biological Chemistry.

[64]  K. Bhakat,et al.  Choreography of oxidative damage repair in mammalian genomes. , 2002, Free radical biology & medicine.

[65]  B. Jeon,et al.  Redox factor-1: an extra-nuclear role in the regulation of endothelial oxidative stress and apoptosis , 2002, Cell Death and Differentiation.

[66]  S. Mitra,et al.  Human AP-endonuclease 1 and hnRNP-L interact with a nCaRE-like repressor element in the AP-endonuclease 1 promoter. , 2002, Nucleic acids research.

[67]  T. Mustelin,et al.  The Egr-1 transcription factor directly activates PTEN during irradiation-induced signalling , 2001, Nature Cell Biology.

[68]  B. Demple,et al.  Key Role of a Downstream Specificity Protein 1 Site in Cell Cycle-regulated Transcription of the AP Endonuclease GeneAPE1/APEX in NIH3T3 Cells* , 2001, The Journal of Biological Chemistry.

[69]  M. Berger,et al.  Apurinic/apyrimidinic endonuclease activity is elevated in human adult gliomas. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[70]  G. Tell,et al.  Prognostic significance of Ape1/ref-1 subcellular localization in non-small cell lung carcinomas. , 2001, Anticancer research.

[71]  G. Dianov,et al.  Interaction of human AP endonuclease 1 with flap endonuclease 1 and proliferating cell nuclear antigen involved in long-patch base excision repair. , 2001, Biochemistry.

[72]  M. Kelley,et al.  Redox regulation of the DNA repair function of the human AP endonuclease Ape1/ref-1. , 2001, Antioxidants & redox signaling.

[73]  M. Kelley,et al.  Activation of APE/Ref-1 redox activity is mediated by reactive oxygen species and PKC phosphorylation. , 2001, Nucleic acids research.

[74]  Jennifer L Hall,et al.  Overexpression of Ref-1 Inhibits Hypoxia and Tumor Necrosis Factor-Induced Endothelial Cell Apoptosis Through Nuclear Factor-&kgr;B—Independent and —Dependent Pathways , 2001, Circulation research.

[75]  M. Stemerman,et al.  Ref-1 and transcriptional control of endothelial apoptosis. , 2001, Circulation research.

[76]  T. Sugawara,et al.  Oxidative Cellular Damage and the Reduction of APE/Ref-1 Expression after Experimental Traumatic Brain Injury , 2001, Neurobiology of Disease.

[77]  K. Gatter,et al.  Nuclear expression of human apurinic/apyrimidinic endonuclease (HAP1/Ref-1) in head-and-neck cancer is associated with resistance to chemoradiotherapy and poor outcome. , 2001, International journal of radiation oncology, biology, physics.

[78]  M. Kelley,et al.  Elevated and altered expression of the multifunctional DNA base excision repair and redox enzyme Ape1/ref-1 in prostate cancer. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[79]  E. Crivellato,et al.  Mitochondrial localization of APE/Ref-1 in thyroid cells. , 2001, Mutation research.

[80]  T. Ulbright,et al.  Altered expression of Ape1/ref-1 in germ cell tumors and overexpression in NT2 cells confers resistance to bleomycin and radiation. , 2001, Cancer research.

[81]  M. Weinfeld,et al.  XRCC1 Stimulates Human Polynucleotide Kinase Activity at Damaged DNA Termini and Accelerates DNA Single-Strand Break Repair , 2001, Cell.

[82]  J. Yodoi,et al.  Thioredoxin nuclear translocation and interaction with redox factor-1 activates the activator protein-1 transcription factor in response to ionizing radiation. , 2000, Cancer research.

[83]  M. Yan,et al.  Induction of ref-1 ensures AP-1 activation in intracellular oxidative environment of IL-2-stimulated BA/F3beta cells. , 2000, Biochemical and biophysical research communications.

[84]  M. Kelley,et al.  Going APE over ref-1. , 2000, Mutation research.

[85]  A. Tomkinson,et al.  Requirement for human AP endonuclease 1 for repair of 3'-blocking damage at DNA single-strand breaks induced by reactive oxygen species. , 2000, Carcinogenesis.

[86]  G. Tell,et al.  TSH controls Ref-1 nuclear translocation in thyroid cells. , 2000, Journal of molecular endocrinology.

[87]  John A. Tainer,et al.  erratum: DNA-bound structures and mutants reveal abasic DNA binding by APE1 and DNA repair coordination , 2000, Nature.

[88]  G. Tell,et al.  An 'environment to nucleus' signaling system operates in B lymphocytes: redox status modulates BSAP/Pax-5 activation through Ref-1 nuclear translocation. , 2000, Nucleic acids research.

[89]  J. Tainer,et al.  DNA-bound structures and mutants reveal abasic DNA binding by APE1 DNA repair and coordination , 2000, Nature.

[90]  L. Poellinger,et al.  Redox-Regulated Recruitment of the Transcriptional Coactivators CREB-Binding Protein and SRC-1 to Hypoxia-Inducible Factor 1α , 2000, Molecular and Cellular Biology.

[91]  T. Sakai,et al.  Thioredoxin-dependent Redox Regulation of p53-mediated p21 Activation* , 1999, The Journal of Biological Chemistry.

[92]  C. Prives,et al.  Ref‐1 regulates the transactivation and pro‐apoptotic functions of p53 in vivo , 1999, The EMBO journal.

[93]  B. Kaina,et al.  Transcriptional activation of apurinic/apyrimidinic endonuclease (Ape, Ref-1) by oxidative stress requires CREB. , 1999, Biochemical and biophysical research communications.

[94]  M. Fujimura,et al.  Early decrease in apurinic/apyrimidinic endonuclease is followed by DNA fragmentation after cold injury-induced brain trauma in mice , 1999, Neuroscience.

[95]  K. Williams,et al.  Atherosclerosis--an inflammatory disease. , 1999, The New England journal of medicine.

[96]  Y. Fujii‐Kuriyama,et al.  Molecular mechanisms of transcription activation by HLF and HIF1α in response to hypoxia: their stabilization and redox signal‐induced interaction with CBP/p300 , 1999, The EMBO journal.

[97]  B. Kaina,et al.  Phosphorylation of the DNA repair protein APE/REF-1 by CKII affects redox regulation of AP-1 , 1999, Oncogene.

[98]  T. Kent,et al.  APE/Ref‐1 responses to ischemia in rat brain , 1998, Neuroreport.

[99]  Harris,et al.  Expression and subcellular localization of human AP endonuclease 1 (HAP1/Ref‐1) protein: a basis for its role in human disease , 1998, Histopathology.

[100]  J. Perez-polo,et al.  APE/Ref‐1 responses to oxidative stress in aged rats , 1998, Journal of neuroscience research.

[101]  J. Girault,et al.  Histone acetyltransferase activity of CBP is controlled by cycle-dependent kinases and oncoprotein E1A , 1998, Nature.

[102]  G. Tell,et al.  Ref-1 controls pax-8 DNA-binding activity. , 1998, Biochemical and biophysical research communications.

[103]  B. Kaina,et al.  Apurinic endonuclease (Ref-1) is induced in mammalian cells by oxidative stress and involved in clastogenic adaptation. , 1998, Cancer research.

[104]  A. Scaloni,et al.  Redox Potential Controls the Structure and DNA Binding Activity of the Paired Domain* , 1998, The Journal of Biological Chemistry.

[105]  Y. Iwamoto,et al.  Nuclear expression of YB-1 protein correlates with P-glycoprotein expression in human osteosarcoma. , 1998, Clinical cancer research : an official journal of the American Association for Cancer Research.

[106]  S. Schreiber,et al.  Immunohistochemical localization of redox factor‐1 (Ref‐1) in Alzheimer's hippocampus , 1998, Neuroreport.

[107]  H. Aburatani,et al.  Mitochondrial targeting of human DNA glycosylases for repair of oxidative DNA damage. , 1998, Nucleic acids research.

[108]  C. Ramana,et al.  Activation of apurinic/apyrimidinic endonuclease in human cells by reactive oxygen species and its correlation with their adaptive response to genotoxicity of free radicals. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[109]  T. Nagaya,et al.  Inductions of immediate early genes (IEGs) and ref‐1 by human chorionic gonadotropin in murine Leydig cell line (MA‐10) , 1998, Biochemistry and molecular biology international.

[110]  Z. Olkowski,et al.  Mutant AP endonuclease in patients with amyotrophic lateral sclerosis , 1998, Neuroreport.

[111]  A. Yacoub,et al.  The DNA repair activity of human redox/repair protein APE/Ref-1 is inactivated by phosphorylation. , 1997, Cancer research.

[112]  K. Hossmann,et al.  Expression of nuclear redox factor ref-1 in the rat hippocampus following global ischemia induced by cardiac arrest. , 1997, Brain research. Molecular brain research.

[113]  D. J. Chen,et al.  Comparison of the promoters of the mouse (APEX) and human (APE) apurinic endonuclease genes. , 1997, Mutation research.

[114]  J. Tainer,et al.  The crystal structure of the human DNA repair endonuclease HAP1 suggests the recognition of extra‐helical deoxyribose at DNA abasic sites , 1997, The EMBO journal.

[115]  M. Kelley,et al.  The apurinic/apyrimidinic endonuclease (APE/ref-1) DNA repair enzyme is elevated in premalignant and malignant cervical cancer. , 1997, Anticancer research.

[116]  H. Seo,et al.  Increase in Ref-1 mRNA and protein by thyrotropin in rat thyroid FRTL-5 cells. , 1997, Biochemical and biophysical research communications.

[117]  H. Krokan,et al.  DNA glycosylases in the base excision repair of DNA. , 1997, The Biochemical journal.

[118]  A. Harris,et al.  Human apurinic endonuclease 1 expression in a colorectal adenoma-carcinoma sequence. , 1997, Cancer research.

[119]  K. Mori,et al.  AP-1 transcriptional activity is regulated by a direct association between thioredoxin and Ref-1. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[120]  G. Kisby,et al.  Evidence of reduced DNA repair in amyotrophic lateral sclerosis brain tissue , 1997, Neuroreport.

[121]  D. Hockenbery,et al.  Down-regulation of apurinic/apyrimidinic endonuclease expression is associated with the induction of apoptosis in differentiating myeloid leukemia cells. , 1997, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[122]  T. Curran,et al.  Identification of redox/repair protein Ref-1 as a potent activator of p53. , 1997, Genes & development.

[123]  P. Gluckman,et al.  Loss of Ref-1 protein expression precedes DNA fragmentation in apoptotic neurons. , 1997, Brain research. Molecular brain research.

[124]  D. Livingston,et al.  Activation of Hypoxia-inducible Transcription Factor Depends Primarily upon Redox-sensitive Stabilization of Its α Subunit* , 1996, The Journal of Biological Chemistry.

[125]  B. Howard,et al.  The Transcriptional Coactivators p300 and CBP Are Histone Acetyltransferases , 1996, Cell.

[126]  S. Mitra,et al.  Negative regulation of the major human AP-endonuclease, a multifunctional protein. , 1996, Biochemistry.

[127]  M. Tanimoto,et al.  Role of the human Y box-binding protein YB-1 in cellular sensitivity to the DNA-damaging agents cisplatin, mitomycin C, and ultraviolet light. , 1996, Cancer research.

[128]  Richard J Smeyne,et al.  The redox/DNA repair protein, Ref-1, is essential for early embryonic development in mice. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[129]  A. Gronenborn,et al.  The solution structure of human thioredoxin complexed with its target from Ref-1 reveals peptide chain reversal. , 1996, Structure.

[130]  E. Ogata,et al.  The Interaction between Ku Antigen and REF1 Protein Mediates Negative Gene Regulation by Extracellular Calcium (*) , 1996, The Journal of Biological Chemistry.

[131]  J. Eble,et al.  Differential cellular and subcellular expression of the human multifunctional apurinic/apyrimidinic endonuclease (APE/ref-1) DNA repair enzyme. , 1995, Cancer research.

[132]  M. Beal,et al.  Aging, energy, and oxidative stress in neurodegenerative diseases , 1995, Annals of neurology.

[133]  S. Ralston,et al.  Origin of a negative calcium response element in an ALU-repeat: implications for regulation of gene expression by extracellular calcium. , 1995, Bone.

[134]  John A. Murphy,et al.  Reactions of oxyl radicals with DNA. , 1995, Free radical biology & medicine.

[135]  M. Dragunow.  Ref-1 expression in adult mammalian neurons and astrocytes , 1995, Neuroscience Letters.

[136]  A. Harris,et al.  A role for the human DNA repair enzyme HAP1 in cellular protection against DNA damaging agents and hypoxic stress. , 1994, Nucleic acids research.

[137]  T. Okazaki,et al.  A redox factor protein, ref1, is involved in negative gene regulation by extracellular calcium. , 1994, The Journal of biological chemistry.

[138]  T. Curran,et al.  Activation of AP-1 and of a nuclear redox factor, Ref-1, in the response of HT29 colon cancer cells to hypoxia. , 1994, Molecular and cellular biology.

[139]  T. Ohmoto,et al.  Stable expression in rat glioma cells of sense and antisense nucleic acids to a human multifunctional DNA repair enzyme, APEX nuclease. , 1994, Mutation research.

[140]  T. Curran,et al.  The redox and DNA-repair activities of Ref-1 are encoded by nonoverlapping domains. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[141]  J. Coyle,et al.  Oxidative stress, glutamate, and neurodegenerative disorders. , 1993, Science.

[142]  C. Robson,et al.  Identification of residues in the human DNA repair enzyme HAP1 (Ref-1) that are essential for redox regulation of Jun DNA binding , 1993, Molecular and cellular biology.

[143]  B. Ames,et al.  Oxidants, antioxidants, and the degenerative diseases of aging. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[144]  I. Roninson,et al.  Induction of multidrug resistance in human cells by transient exposure to different chemotherapeutic drugs. , 1993, Journal of the National Cancer Institute.

[145]  D. Ward,et al.  Human apurinic endonuclease gene (APE): structure and genomic mapping (chromosome 14q11.2-12). , 1992, Human molecular genetics.

[146]  T. Curran,et al.  Redox activation of Fos‐Jun DNA binding activity is mediated by a DNA repair enzyme. , 1992, The EMBO journal.

[147]  T. Curran,et al.  Identification and characterization of Ref‐1, a nuclear protein that facilitates AP‐1 DNA‐binding activity. , 1992, The EMBO journal.

[148]  B. Demple,et al.  Two distinct human DNA diesterases that hydrolyze 3'-blocking deoxyribose fragments from oxidized DNA. , 1991, Nucleic acids research.

[149]  K. Nose,et al.  Transcriptional activation of early-response genes by hydrogen peroxide in a mouse osteoblastic cell line. , 1991, European journal of biochemistry.

[150]  D. Ganten,et al.  Morphology, physiology, and molecular biology of renin secretion. , 1990, Physiological reviews.

[151]  R. Cunningham,et al.  The enzymology of apurinic/apyrimidinic endonucleases. , 1990, Mutation research.

[152]  H. Takano,et al.  The direct activation of human multidrug resistance gene (MDR1) by anticancer agents. , 1989, Biochemical and biophysical research communications.

[153]  E. Ogata,et al.  Hypocalcemia increases and hypercalcemia decreases the steady-state level of parathyroid hormone messenger RNA in the rat. , 1989, The Journal of clinical investigation.

[154]  Lin Yuan,et al.  What is the solution? , 1984, Nature.

[155]  T. Liu,et al.  Demonstration of the presence of a histidine residue at the active site of streptococcal proteinase. , 1967, The Journal of biological chemistry.

[156]  A. Leonardi,et al.  TRAF2 and p38 are involved in B cells CD40-mediated APE/Ref-1 nuclear translocation: a novel pathway in B cell activation. , 2008, Molecular immunology.

[157]  K. Bhakat,et al.  Acetylation of human AP-endonuclease 1, a critical enzyme in DNA repair and transcription regulation. , 2003, Methods in enzymology.

[158]  L. Martin,et al.  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 , 2002, NeuroMolecular Medicine.

[159]  K. Kataoka,et al.  Spatial redox regulation of a critical cysteine residue of NF-kappa B in vivo. , 2002, The Journal of biological chemistry.

[160]  E. J. Song,et al.  Regulation and destabilization of HIF-1alpha by ARD1-mediated acetylation. , 2002, Cell.

[161]  Samuel H. Wilson,et al.  Mammalian DNA β-polymerase in base excision repair of alkylation damage , 2001 .

[162]  S. H. Wilson,et al.  Mammalian DNA beta-polymerase in base excision repair of alkylation damage. , 2001, Progress in nucleic acid research and molecular biology.

[163]  Linrong Lu,et al.  Ubiquitin Conjugating Enzyme Ubc9 is Involved in Protein Degradation of Redox Factor-1 (Ref-1). , 2000, Sheng wu hua xue yu sheng wu wu li xue bao Acta biochimica et biophysica Sinica.

[164]  J. Tainer,et al.  DNA-bound structures and mutants reveal abasic DNA binding by APE1 and DNA repair coordination [corrected]. , 2000, Nature.

[165]  A. Puga,et al.  Regulation of gene expression by reactive oxygen. , 1999, Annual review of pharmacology and toxicology.

[166]  B. Dörken,et al.  Nuclear localization and increased levels of transcription factor YB-1 in primary human breast cancers are associated with intrinsic MDR1 gene expression , 1997, Nature Medicine.

[167]  B Demple,et al.  Repair of oxidative damage to DNA: enzymology and biology. , 1994, Annual review of biochemistry.

[168]  L. Loeb,et al.  Mutagenesis by apurinic/apyrimidinic sites. , 1986, Annual review of genetics.