A redox factor protein, ref1, is involved in negative gene regulation by extracellular calcium.

A rise in extracellular calcium (Ca2+e) suppresses not only secretion of parathyroid hormone (PTH) but also expression of the PTH gene to ensure constant plasma Ca2+ level. A nuclear protein(s) in a wide variety of cells bound to the specific DNA elements (negative Ca2+ responsive elements, nCaREs) in the human PTH gene in sequence-specific and Ca2+e concentration-dependent manners. 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 nCaRE binding protein. The level of ref1 mRNA as well as of its protein was elevated by an increase in Ca2+e concentration. In gel shift assay, anti-ref1 antibody eliminated formation of the nCaRE-protein complex. We also found that there was another protein(s) interacting with nCaREs and ref1. Further, experiments with an antisense-ref cDNA expression vector introduced into cultured cells suggested that DNA (nCaRE)-ref1 interaction led to Ca2+e-mediated transcriptional suppression. Thus, it is concluded that ref1 possesses transcription repressor activity in addition to its function as a transcriptional auxiliary protein.

• Publication year

  1994

• Venue

  Journal of Biological Chemistry

• Publication date

  1994-11-11

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1016/s0021-9258(18)46865-2PMID 7961715
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Identification of residues in the human DNA repair enzyme HAP1 (Ref-1) that are essential for redox regulation of Jun DNA binding

  1993cited by this paper
• Steroid hormone receptors: interaction with deoxyribonucleic acid and transcription factors.

  1993cited by this paper
• Regulation of gene expression in hippocampal neurons by distinct calcium signaling pathways.

  1993cited by this paper
• Cyclic adenosine 3',5'-monophosphate response element binding protein (CREB) and related transcription-activating deoxyribonucleic acid-binding proteins.

  1993cited by this paper
• Platelet-derived growth factor B chain promoter contains a cis-acting fluid shear-stress-responsive element.

  1993cited by this paper
• Cloning and characterization of an extracellular Ca2+-sensing receptor from bovine parathyroid

  1993cited by this paper
• Transcription factors: structural families and principles of DNA recognition.

  1992cited by this paper
• Retinoid X receptor is an auxiliary protein for thyroid hormone and retinoic acid receptors

  1992cited by this paper
• The regulation of transcription by phosphorylation.

  1992cited by this paper
• Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling

  1992cited by this paper
• Conserved mechanism of negative gene regulation by extracellular calcium. Parathyroid hormone gene versus atrial natriuretic polypeptide gene.

  1992cited by this paper
• All-trans and 9-cis retinoic acid induction of CRABPII transcription is mediated by RAR-RXR heterodimers bound to DR1 and DR2 repeated motifs.

  1992cited by this paper
• Endothelin induces transcription of fos/jun family genes: a prominent role for calcium ion.

  1992cited by this paper
• p53 function and dysfunction.

  1992cited by this paper
• Calcium signaling in cell volume regulation.

  1992cited by this paper
• Calcium-Regulated Phosphorylation Within the Leucine Zipper of C/EBPβ

  1992cited by this paper
• Regulation of parathyroid hormone-related peptide (PTHrP) gene transcription: cell- and tissue-specific promoter utilization mediated by multiple positive and negative cis-acting DNA elements.

  1992cited by this paper
• Redox activation of Fos‐Jun DNA binding activity is mediated by a DNA repair enzyme.

  1992cited by this paper
• Negative regulatory elements in the human parathyroid hormone gene.

  1991cited by this paper
• CREB: a Ca(2+)-regulated transcription factor phosphorylated by calmodulin-dependent kinases.

  1991cited by this paper
• Calcium/calmodulin-dependent protein kinase mediates a pathway for transcriptional regulation.

  1991cited by this paper
• Inhibition of cAMP accumulation by intracellular calcium mobilization in C6-2B cells stably transfected with substance K receptor cDNA.

  1991cited by this paper
• Pit-1 binding sequences permit calcium regulation of human prolactin gene expression.

  1991cited by this paper
• Isolation of cDNA clones encoding a human apurinic/apyrimidinic endonuclease that corrects DNA repair and mutagenesis defects in E. coli xth (exonuclease III) mutants.

  1991cited by this paper
• Extracellular Ca2+ sensing, regulation of parathyroid cell function, and role of Ca2+ and other ions as extracellular (first) messengers.

  1991cited by this paper
• Transcriptional interference between c-Jun and the glucocorticoid receptor: mutual inhibition of DNA binding due to direct protein-protein interaction.

  1990cited by this paper
• Negative and positive regulation by transcription factor cAMP response element-binding protein is modulated by phosphorylation.

  1990cited by this paper
• Hyposmolarity stimulates myeloperoxidase exocytosis from human polymorphonuclear leukocytes.

  1990cited by this paper
• Transcriptional regulation by dimerization: two sides to an incestuous relationship.

  1990cited by this paper
• A cluster of phosphorylation sites on the cyclic AMP-regulated nuclear factor CREB predicted by its sequence

  1989cited by this paper
• How do different transcription factors binding the same DNA sequence sort out their jobs?

  1989cited by this paper
• Hypocalcemia increases and hypercalcemia decreases the steady-state level of parathyroid hormone messenger RNA in the rat.

  1989cited by this paper
• A spatial-temporal model of cell activation.

  1988cited by this paper
• Cyclic AMP-responsive DNA-binding protein: structure based on a cloned placental cDNA.

  1988cited by this paper
• Fos and Jun: the AP-1 connection.

  1988cited by this paper
• 5'-flanking region of the parathyroid hormone gene mediates negative regulation by 1,25-(OH)2 vitamin D3.

  1988cited by this paper
• High osmolality: a potent parathyroid hormone secretogogue in dispersed parathyroid cells.

  1987cited by this paper
• Replacement of insulin receptor tyrosine residues 1162 and 1163 compromises insulin-stimulated kinase activity and uptake of 2-deoxyglucose.

  1986cited by this paper
• CAT vectors for analysis of eukaryotic promoters and enhancers.

  1986cited by this paper
• Studies and perspectives of protein kinase C.

  1986cited by this paper
• Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei.

  1983cited by this paper
• DNA sequencing with chain-terminating inhibitors.

  1977cited by this paper

• A Dynamic Search Mechanism Enables APE1 to Identify AP-Sites in DNA

  2026cites this paper
• Potential Role of APEX1 During Ferroptosis

  2022cites this paper
• The human AP-endonuclease 1 (APE1) is a DNA G-quadruplex structure binding protein and regulates KRAS expression in pancreatic ductal adenocarcinoma cells

  2022cites this paper
• Molecular Mechanisms Regulating the DNA Repair Protein APE1: A Focus on Its Flexible N-Terminal Tail Domain

  2021cites this paper
• Arginine methylation of APE1 promotes its mitochondrial translocation to protect cells from oxidative damage

  2020cites this paper
• Additional functions of selected proteins involved in DNA repair.

  2019cites this paper
• The Role of Histone Chaperone FACT Complex in Base Excision Repair Pathway and Its Therapeutic Potential in Colon Cancer and Medulloblastoma

  2019cites this paper
• Mechanism of stimulation of DNA binding of the transcription factors by human apurinic/apyrimidinic endonuclease 1, APE1.

  2019cites this paper
• Reading targeted DNA damage in the active demethylation pathway: role of accessory domains of eukaryotic AP endonucleases and thymine-DNA glycosylases.

  2019cites this paper
• Ape1 guides DNA repair pathway choice that is associated with drug tolerance in glioblastoma

  2017cites this paper
• An Excess of CYP24A1, Lack of CaSR, and a Novel lncRNA Near the PTH Gene Characterize an Ectopic PTH-Producing Tumor

  2017cites this paper
• Tumor‐associated APE1 variant exhibits reduced complementation efficiency but does not promote cancer cell phenotypes

  2017cites this paper
• 2-1-2014 Repair of Oxidative DNA Damage and Cancer : Recent Progress in DNA Base Excision Repair

  2017cites this paper
• Regulation of limited N-terminal proteolysis of APE1 in tumor via acetylation and its role in cell proliferation

  2016cites this paper
• Resisting the Resistance in Cancer: Cheminformatics Studies on Short- Path Base Excision Repair Pathway Antagonists Using Supervised Learning Approaches.

  2015cites this paper
• Recognition and repair of chemically heterogeneous structures at DNA ends

  2015cites this paper
• Downregulation of the DNA repair enzyme apurinic/apyrimidinic endonuclease 1 stimulates transforming growth factor-β1 production and promotes actin rearrangement.

  2015cites this paper
• Parathyroid Hormone Gene

  2015cites this paper
• Regulatory mechanisms of RNA function: emerging roles of DNA repair enzymes

  2014cites this paper
• Human Apurinic/Apyrimidinic Endonuclease 1

  2014cites this paper
• Repair of Oxidative DNA Damage and Cancer: Recent Progress in DNA Base Excision Repair

  2014cites this paper
• Functional variants of human APE1 rescue the DNA repair defects of the yeast AP endonuclease/3'-diesterase-deficient strain.

  2014cites this paper
• Apurinic/apyrimidinic endonuclease 1 is a key modulator of aluminum-induced neuroinflammation

  2013cites this paper
• Essential role for mammalian apurinic/apyrimidinic (AP) endonuclease Ape1/Ref-1 in telomere maintenance

  2013cites this paper
• Dual Regulatory Roles of Human AP-Endonuclease (APE1/Ref-1) in CDKN1A/p21 Expression

  2013cites this paper
• Receptor‐Based Virtual Screening and Biological Characterization of Human Apurinic/Apyrimidinic Endonuclease (Ape1) Inhibitors

  2012cites this paper
• Base excision repair: contribution to tumorigenesis and target in anticancer treatment paradigms.

  2012cites this paper
• MINISTÉRIO DA EDUCAÇÃO UNIVERSIDADE FEDERAL DO RIO GRANDE DO NORTE

  2012cites this paper
• Blockade of Base Excision Repair: Inhibition of Small Lesions Results in Big Consequences to Cancer Cells

  2012cites this paper
• Personalized Cancer Medicine

  2012cites this paper
• APE1/Ref-1 role in redox signaling: translational applications of targeting the redox function of the DNA repair/redox protein APE1/Ref-1.

  2012cites this paper
• Regulation of mouse-renin gene by apurinic/apyrimidinic-endonuclease 1 (APE1/Ref-1) via recruitment of histone deacetylase 1 corepressor complex

  2012influential citation
• Two‐Photon Fluorescent Imaging of Myelination in the Spinal Cord

  2012cites this paper
• APEX1 Regulation of Aldosterone Synthase Gene Transcription Is Disrupted by a Common Polymorphism in Humans

  2012cites this paper
• NMR studies reveal an unexpected binding site for a redox inhibitor of AP endonuclease 1.

  2011cites this paper
• Ubiquitination of human AP-endonuclease 1 (APE1) enhanced by T233E substitution and by CDK5

  2011cites this paper
• Development and evaluation of human AP endonuclease inhibitors in melanoma and glioma cell lines

  2011cites this paper
• Neurons Efficiently Repair Glutamate-induced Oxidative DNA Damage by a Process Involving CREB-mediated Up-regulation of Apurinic Endonuclease 1*

  2010cites this paper
• Tissue‐specific regulatory regions of the PTH gene localized by novel chromosome 11 rearrangement breakpoints in a parathyroid adenoma

  2010cites this paper
• Dual regulation by apurinic/apyrimidinic endonuclease-1 inhibits gastric epithelial cell apoptosis during Helicobacter pylori infection.

  2010cites this paper
• Inhibition of Ape1's DNA Repair Activity as a Target in Cancer: Identification of Novel Small Molecules that have Translational Potential for Molecularly Targeted Cancer Therapy

  2010cites this paper
• The role of GAPDH in maintaining the functional state of the DNA repair enzyme APE1

  2010cites this paper
• Regulation of DNA Damage Processing by Covalent Modification of Thymine DNA Glycosylase

  2010cites this paper
• SIRT 1 deacetylates APE 1 and regulates cellular base excision repair

  2010cites this paper
• Endoribonucleases – enzymes gaining spotlight in mRNA metabolism

  2010cites this paper
• Involvement of GCMB in the transcriptional regulation of the human parathyroid hormone gene in a parathyroid-derived cell line PT-r: effects of calcium and 1,25(OH)2D3.

  2010influential citation
• Understanding different functions of mammalian AP endonuclease (APE1) as a promising tool for cancer treatment

  2010cites this paper
• Posttranslational modification of mammalian AP endonuclease (APE1)

  2010cites this paper
• Human AP endonuclease 1 (APE1): from mechanistic insights to druggable target in cancer.

  2010cites this paper
• Human AP-endonuclease (APE1/Ref-1) and its acetylation regulate YB-1/p300 recruitment and RNA polymerase II loading in the drug induced activation of multidrug resistance gene MDR1

  2010cites this paper
• A novel regulatory circuit in base excision repair involving AP endonuclease 1, Creb1 and DNA polymerase β

  2010cites this paper
• Ubiquitination of mammalian AP endonuclease (APE1) regulated by the p53-MDM2 signaling pathway

  2009cites this paper
• Transcriptional Regulatory Functions of Mammalian AP-Endonuclease (APE1/Ref-1), an Essential Multifunctional Protein

  2009influential citation
• SIRT1 deacetylates APE1 and regulates cellular base excision repair

  2009cites this paper
• Acetylation of apurinic/apyrimidinic endonuclease-1 regulates Helicobacter pylori-mediated gastric epithelial cell apoptosis.

  2009cites this paper
• Going Ape as an Approach to Cancer Therapeutics

  2009cites this paper
• Ape1/Ref-1 Induces Glial Cell-Derived Neurotropic Factor (GDNF) Responsiveness by Upregulating GDNF Receptor α1 Expression

  2009cites this paper
• APE1/Ref-1: Versatility in Progress

  2009cites this paper
• Regulation of the human AP-endonuclease (APE1/Ref-1) expression by the tumor suppressor p53 in response to DNA damage

  2008cites this paper
• Opposite Effect of Phorbol Ester PMA on PTGS2 and PGDH mRNA Expression in Human Chorion Trophoblast Cells

  2008cites this paper
• Unusual role of a cysteine residue in substrate binding and activity of human AP-endonuclease 1.

  2008cites this paper
• Regulatory Role of Human AP-Endonuclease (APE1/Ref-1) in YB-1-Mediated Activation of the Multidrug Resistance Gene MDR1

  2008cites this paper
• 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

  2008cites this paper
• Pathology of the Parathyroid

  2008cites this paper
• Mdr1 Resistance Gene Yb-1-mediated Activation of the Multidrug Ap-endonuclease (ape1/ref-1) in Regulatory Role of Human Supplemental Material

  2008cites this paper
• The DNA base excision repair protein Ape1/Ref-1 as a therapeutic and chemopreventive target.

  2007cites this paper
• Gene Regulation by Extracellular Vitamin D and Osmolarity Calcium

  2006cites this paper
• APE / Ref-1 Is Inactivated by Phosphorylation The DNA Repair Activity of Human Redox / Repair Protein

  2006cites this paper
• Identification and characterization of mitochondrial abasic (AP)-endonuclease in mammalian cells

  2006cites this paper
• Kaina by Oxidative Stress and Involved in Clastogenic Adaptation Apurinic Endonuclease ( Ref-1 ) Is Induced in Mammalian Cells

  2006cites this paper
• Analysis of nuclear transport signals in the human apurinic/apyrimidinic endonuclease (APE1/Ref1)

  2005cites this paper
• Molecular and biological roles of Ape1 protein in mammalian base excision repair.

  2005cites this paper
• Two essential but distinct functions of the mammalian abasic endonuclease.

  2005cites this paper
• In Silico Analysis of Regulatory Sequences in the Human Parathyroid Hormone Gene

  2005cites this paper
• The Intracellular Localization of APE1/Ref-1: More than a Passive Phenomenon?

  2005cites this paper
• Effect of aging on intracellular distribution of abasic (AP) endonuclease 1 in the mouse liver.

  2005cites this paper
• Human AP endonuclease suppresses DNA mismatch repair activity leading to microsatellite instability

  2005cites this paper
• Identification and Characterization of cis‐Acting Elements in the Human and Bovine PTH mRNA 3′‐Untranslated Region

  2004cites this paper
• Blood pressure control goes nuclear.

  2004cites this paper
• Age-dependent modulation of DNA repair enzymes by covalent modification and subcellular distribution.

  2004influential citation
• Suppression of the Human Parathyroid Hormone Promoter by Vitamin D Involves Displacement of NF-Y Binding to the Vitamin D Response Element*

  2004cites this paper
• Modulation of the 5′-Deoxyribose-5-phosphate Lyase and DNA Synthesis Activities of Mammalian DNA Polymerase β by Apurinic/Apyrimidinic Endonuclease 1*

  2004cites this paper
• Effects of backbone contacts 3' to the abasic site on the cleavage and the product binding by human apurinic/apyrimidinic endonuclease (APE1).

  2004cites this paper
• AP endonuclease-independent DNA base excision repair in human cells.

  2004cites this paper
• Base excision repair.

  2004cites this paper
• 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

  2004cites this paper
• Intracellular Ca2+ and renin gene transcription.

  2003cites this paper
• Vitamin D-dependent recruitment of DNA-PK to the chromatinized negative vitamin D response element in the PTHrP gene is required for gene repression by vitamin D.

  2003cites this paper
• Sp3/Sp1 in the parathyroid gland: identification of an Sp1 deoxyribonucleic acid element in the parathyroid hormone promoter.

  2003cites this paper
• Acetylation of human AP-endonuclease 1, a critical enzyme in DNA repair and transcription regulation.

  2003cites this paper
• CHAPTER 28 – Renal Osteodystrophy: Pathogenesis, Diagnosis, and Treatment

  2003cites this paper
• Role of acetylated human AP‐endonuclease (APE1/Ref‐1) in regulation of the parathyroid hormone gene

  2003influential citation
• Implication of Ref-1 in the repression of renin gene transcription by intracellular calcium

  2003cites this paper
• Modulation of the 3′→5′-Exonuclease Activity of Human Apurinic Endonuclease (Ape1) by Its 5′-incised Abasic DNA Product*

  2003cites this paper
• An investigation of genotoxicity and antioxidant treatment of DNA repair in human cells

  2002cites this paper
• Calcium-sensing receptor gene polymorphism affects the parathyroid response to moderate hypercalcemic suppression in patients with end-stage renal disease.

  2002cites this paper
• Analysis and quantitation of ceramide.

  2002cites this paper
• The Parathyroid Gland

  2002cites this paper
• Cell biology of renal osteodystrophy

  2002cites this paper
• APE/Ref-1 is Controlled by Both Redox and cAMP-Dependent Mechanisms in Rat Thyroid Cells

  2002cites this paper