Research Topics
Genomes and Genes
| John D HayesSummaryAffiliation: University of Dundee Country: UK Publications
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Detail Information
Publications
Nrf2 orchestrates fuel partitioning for cell proliferationJohn D Hayes
Jacqui Wood Cancer Centre, Division of Cancer Research, Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK
Cell Metab 16:139-41. 2012..This change in cellular metabolism requires loss of Nrf2 repression by Keap1 as well as costimulation via the PI3K-Akt pathway...- Cancer chemoprevention mechanisms mediated through the Keap1-Nrf2 pathwayJohn D Hayes
Biomedical Research Institute, Ninewells Hospital, University of Dundee, Scotland, United Kingdom
Antioxid Redox Signal 13:1713-48. 2010.... - NRF2 and KEAP1 mutations: permanent activation of an adaptive response in cancerJohn D Hayes
Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK
Trends Biochem Sci 34:176-88. 2009..Moreover, constitutive NRF2 activation might cause drug resistance in tumours, and an understanding of how the transcription factor is regulated indicates ways in which this could be overcome... - The cancer chemopreventive actions of phytochemicals derived from glucosinolatesJohn D Hayes
Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK
Eur J Nutr 47:73-88. 2008..Certain indoles act as ligands for AhR. Isothiocyanates and indoles are also capable of affecting cell cycle arrest and stimulating apoptosis. The mechanisms responsible for these anti-proliferative responses are discussed... 
Negative regulation of the Nrf1 transcription factor by its N-terminal domain is independent of Keap1: Nrf1, but not Nrf2, is targeted to the endoplasmic reticulumYiguo Zhang
Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK
Biochem J 399:373-85. 2006..Thus Nrf1 and Nrf2 are targeted to different subcellular compartments and are negatively regulated by distinct mechanisms...
Redox-regulated turnover of Nrf2 is determined by at least two separate protein domains, the redox-sensitive Neh2 degron and the redox-insensitive Neh6 degronMichael McMahon
Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, United Kingdom
J Biol Chem 279:31556-67. 2004..A model can now be proposed to explain how the turnover of this protein adapts in response to alterations in cellular redox state...- Identification of retinoic acid as an inhibitor of transcription factor Nrf2 through activation of retinoic acid receptor alphaXiu Jun Wang
Cancer Research U K Molecular Pharmacology Unit, Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, United Kingdom
Proc Natl Acad Sci U S A 104:19589-94. 2007..These data suggest that cross-talk between Nrf2 and RARalpha could markedly influence the sensitivity of cells to electrophiles and oxidative stressors and, as a consequence, to carcinogenesis... - Induction of cancer chemopreventive enzymes by coffee is mediated by transcription factor Nrf2. Evidence that the coffee-specific diterpenes cafestol and kahweol confer protection against acroleinLarry G Higgins
Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, Scotland, UK
Toxicol Appl Pharmacol 226:328-37. 2008..Priming of nrf2(+/+) MEFs, but not nrf2(-/-) MEFs, with C+K conferred 2-fold resistance towards acrolein... - 1-Cyano-2,3-epithiopropane is a novel plant-derived chemopreventive agent which induces cytoprotective genes that afford resistance against the genotoxic alpha,beta-unsaturated aldehyde acroleinMichael O Kelleher
Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Scotland, UK
Carcinogenesis 30:1754-62. 2009..4-fold resistance against subsequent exposure to the alpha,beta-unsaturated aldehyde acrolein, indicating that the phytochemical exerts chemopreventive properties against genotoxic xenobiotics... - Dimerization of substrate adaptors can facilitate cullin-mediated ubiquitylation of proteins by a "tethering" mechanism: a two-site interaction model for the Nrf2-Keap1 complexMichael McMahon
Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, United Kingdom
J Biol Chem 281:24756-68. 2006..We show that self-association is a general feature of Cul3 substrate adaptors and propose that the fixed-ends mechanism is commonly utilized to recruit, orientate, and ubiquitylate substrates upon this family of ubiquitin ligases... - Transcription factor Nrf2 mediates an adaptive response to sulforaphane that protects fibroblasts in vitro against the cytotoxic effects of electrophiles, peroxides and redox-cycling agentsLarry G Higgins
Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK
Toxicol Appl Pharmacol 237:267-80. 2009..Thus Nrf2-dependent up-regulation of GSH is the principal mechanism by which sulforaphane pre-treatment induced resistance to acrolein, CuOOH and chlorambucil, but not menadione... - The Nrf3 transcription factor is a membrane-bound glycoprotein targeted to the endoplasmic reticulum through its N-terminal homology box 1 sequenceYiguo Zhang
Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, UK
J Biol Chem 284:3195-210. 2009..Lastly, data are presented suggesting that the NHB2 sequence in mouse Nrf3 may regulate the topology of the transcription factor within the ER membrane... - Activation of the NRF2 signaling pathway by copper-mediated redox cycling of para- and ortho-hydroquinonesXiu Jun Wang
Cancer Research UK Molecular Pharmacology Unit, Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, UK
Chem Biol 17:75-85. 2010..Thus, the oxidation of para- and ortho-hydroquinones to quinones represents the rate-limiting step in the activation of Nrf2... - Identification of topological determinants in the N-terminal domain of transcription factor Nrf1 that control its orientation in the endoplasmic reticulum membraneYiguo Zhang
Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Scotland, UK
Biochem J 430:497-510. 2010..Thus Nrf1 can adopt several topologies within membranes that are determined by its NTD... - Utility of siRNA against Keap1 as a strategy to stimulate a cancer chemopreventive phenotypeTim W P Devling
Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, United Kingdom
Proc Natl Acad Sci U S A 102:7280-7285A. 2005..75-fold increase in intracellular glutathione 48 h after transfection. Thus, antagonism of Keap1 by siRNA can be used to preadapt human cells to oxidative stress without the need to expose them to redox stressors... - Transcription factor Nrf2 is essential for induction of NAD(P)H:quinone oxidoreductase 1, glutathione S-transferases, and glutamate cysteine ligase by broccoli seeds and isothiocyanatesGail K McWalter
Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, United Kingdom
J Nutr 134:3499S-3506S. 2004..These experiments show that broccoli seeds are effective at inducing antioxidant and detoxication proteins, both in vivo and ex vivo, in an Nrf2-dependent manner... - Expression of the aflatoxin B1-8,9-epoxide-metabolizing murine glutathione S-transferase A3 subunit is regulated by the Nrf2 transcription factor through an antioxidant response elementIan R Jowsey
Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK
Mol Pharmacol 64:1018-28. 2003..Collectively, these data demonstrate a role for Nrf2 and the ARE in regulating transcription of mGSTA3... - Expression and localization of rat aldo-keto reductases and induction of the 1B13 and 1D2 isoforms by phenolic antioxidantsA Kenneth MacLeod
Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK
Drug Metab Dispos 38:341-6. 2010..Here we identify AKR1B13 and AKR1D2 as further inducible members of the rat AKR superfamily... - Identification of a novel Nrf2-regulated antioxidant response element (ARE) in the mouse NAD(P)H:quinone oxidoreductase 1 gene: reassessment of the ARE consensus sequencePaul Nioi
Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK
Biochem J 374:337-48. 2003..Furthermore, our results indicate that distinct AREs have differential sequence requirements, and a universally applicable consensus sequence cannot be derived... - Tissue-specific expression and subcellular distribution of murine glutathione S-transferase class kappaRachel E Thomson
Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, United Kingdom
J Histochem Cytochem 52:653-62. 2004..These results are consistent with a role for mGST K1-1 in detoxification, and the confirmation of the intramitochondrial localization of this enzyme implies a unique role for GST class kappa as an antioxidant enzyme... - Characterization of the cancer chemopreventive NRF2-dependent gene battery in human keratinocytes: demonstration that the KEAP1-NRF2 pathway, and not the BACH1-NRF2 pathway, controls cytoprotection against electrophiles as well as redox-cycling compoundsA Kenneth MacLeod
Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK
Carcinogenesis 30:1571-80. 2009..This study also shows that AKR1B10, AKR1C1 and AKR1C2 proteins have potential utility as biomarkers for NRF2 activation in the human... - Novel homodimeric and heterodimeric rat gamma-hydroxybutyrate synthases that associate with the Golgi apparatus define a distinct subclass of aldo-keto reductase 7 family proteinsVincent P Kelly
Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Scotland, UK
Biochem J 366:847-61. 2002.... - The Nrf1 CNC/bZIP protein is a nuclear envelope-bound transcription factor that is activated by t-butyl hydroquinone but not by endoplasmic reticulum stressorsYiguo Zhang
Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee DD19SY, Scotland, UK
Biochem J 418:293-310. 2009..Collectively, these results suggest that the activity of Nrf1 critically depends on its topology within the ER, and that this is modulated by redox stressors, as well as by its glycosylation status... - Contribution of NAD(P)H:quinone oxidoreductase 1 to protection against carcinogenesis, and regulation of its gene by the Nrf2 basic-region leucine zipper and the arylhydrocarbon receptor basic helix-loop-helix transcription factorsPaul Nioi
Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, United Kingdom
Mutat Res 555:149-71. 2004..The XRE recruits the arylhydrocarbon receptor (AhR) and AhR nuclear translocator. Cross-talk may occur between Nrf2 and AhR, but the details of this process remain to be elucidated... - Loss of the Nrf2 transcription factor causes a marked reduction in constitutive and inducible expression of the glutathione S-transferase Gsta1, Gsta2, Gstm1, Gstm2, Gstm3 and Gstm4 genes in the livers of male and female miceSimon A Chanas
Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK
Biochem J 365:405-16. 2002..These data also indicate that attenuated induction of GSH-dependent enzymes in Nrf2(-/-) mice probably accounts for their failure to adapt to chronic exposure to chemical and oxidative stress... - Loss of Nrf2 markedly exacerbates nonalcoholic steatohepatitisSudhir Chowdhry
Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK
Free Radic Biol Med 48:357-71. 2010..Thus, impairment of Nrf2 activity may represent a major risk factor for the evolution of NAFLD to NASH... - The NHB1 (N-terminal homology box 1) sequence in transcription factor Nrf1 is required to anchor it to the endoplasmic reticulum and also to enable its asparagine-glycosylationYiguo Zhang
Biomedical Research Center, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK
Biochem J 408:161-72. 2007..Wild-type Nrf1 is glycosylated through its Asn/Ser/Thr-rich domain, between amino acids 296 and 403, and this modification was not observed in an Nrf1(Delta299-400) mutant. Glycosylation of Nrf1 was not necessary to retain it in the ER... - The double-edged sword of Nrf2: subversion of redox homeostasis during the evolution of cancerJohn D Hayes
Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, United Kingdom
Mol Cell 21:732-4. 2006..Surprisingly, Padmanabhan et al. (2006) provide evidence in a recent issue of Molecular Cell to support the notion that elevated Nrf2 activity may also play a role in the evolution of cancer... - Generation of a stable antioxidant response element-driven reporter gene cell line and its use to show redox-dependent activation of nrf2 by cancer chemotherapeutic agentsXiu Jun Wang
Cancer Research UK Molecular Pharmacology Unit and Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, United Kingdom
Cancer Res 66:10983-94. 2006..Our findings show that Nrf2 can be activated by certain anticancer agents, and this will influence the effectiveness of chemotherapy... - Keap1 perceives stress via three sensors for the endogenous signaling molecules nitric oxide, zinc, and alkenalsMichael McMahon
Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland
Proc Natl Acad Sci U S A 107:18838-43. 2010.... - Mechanisms of induction of cytosolic and microsomal glutathione transferase (GST) genes by xenobiotics and pro-inflammatory agentsLarry G Higgins
Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, United Kingdom
Drug Metab Rev 43:92-137. 2011..We discuss cross-talk between the different induction mechanisms, and have employed bioinformatics to identify cis-elements in the upstream regions of GST genes to which the various transcription factors mentioned above may be recruited... - Positive and negative regulation of prostaglandin E2 biosynthesis in human colorectal carcinoma cells by cancer chemopreventive agentsPhilip J Sherratt
Biomedical Research Centre, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, UK
Biochem Pharmacol 66:51-61. 2003..Importantly, dietary compounds can modulate PGE(2) biosynthesis, and this is likely to influence colon tumorigenesis... - Expression of the murine glutathione S-transferase alpha3 (GSTA3) subunit is markedly induced during adipocyte differentiation: activation of the GSTA3 gene promoter by the pro-adipogenic eicosanoid 15-deoxy-Delta12,14-prostaglandin J2Ian R Jowsey
Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK
Biochem Biophys Res Commun 312:1226-35. 2003..These data suggest a previously unrecognised role for GSTs in mouse adipocytes... - Prostaglandin D2 synthase enzymes and PPARgamma are co-expressed in mouse 3T3-L1 adipocytes and human tissuesIan R Jowsey
Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK
Prostaglandins Other Lipid Mediat 70:267-84. 2003..These data reveal the potential for de novo 15-d-PGJ2 synthesis in the context of PPARgamma expression, suggesting that this prostaglandin may contribute to PPARgamma signalling in vivo... - Direct comparison of the nature of mouse and human GST T1-1 and the implications on dichloromethane carcinogenicityPhilip J Sherratt
Biomedical Research Centre, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland, DD1 9SY, United Kingdom
Toxicol Appl Pharmacol 179:89-97. 2002..Taking this information into account, it is unlikely that humans have a sufficiently high capacity to activate DCM for this compound to be considered to represent a carcinogenic risk... - The cap'n'collar transcription factor Nrf2 mediates both intrinsic resistance to environmental stressors and an adaptive response elicited by chemopreventive agents that determines susceptibility to electrophilic xenobioticsLarry G Higgins
Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, United Kingdom
Chem Biol Interact 192:37-45. 2011..However, inducible resistance towards menadione that occurred upon pre-treatment with 3μM Sul was independent of glutathione and may be due to upregulation of Nqo1. Thus Nrf2 controls cellular resistance against electrophiles... - Keap1-dependent proteasomal degradation of transcription factor Nrf2 contributes to the negative regulation of antioxidant response element-driven gene expressionMichael McMahon
Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, United Kingdom
J Biol Chem 278:21592-600. 2003..Within Nrf2, the N-terminal Neh2 domain is identified as the redox-sensitive degron. These data suggest that Keap1 negatively regulates Nrf2 by both enhancing its rate of proteasomal degradation and altering its subcellular distribution... - Glutathione transferasesJohn D Hayes
Biomedical Research Center, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, United Kingdom
Annu Rev Pharmacol Toxicol 45:51-88. 2005..Consistent with this hypothesis, the promoters of cytosolic GST and MAPEG genes contain antioxidant response elements through which they are transcriptionally activated during exposure to Michael reaction acceptors and oxidative stress... - Biochemical and genetic characterization of a murine class Kappa glutathione S-transferaseIan R Jowsey
Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK
Biochem J 373:559-69. 2003..Furthermore, the association of these enzymes with mitochondrial fractions is consistent with them performing a specific conserved biological role within this organelle... - Alteration of glutathione S-transferase levels in Barrett's metaplasia compared to normal oesophageal epitheliumSarah C Cobbe
Department of Molecular and Cellular Pathology, Biomedical Research Centre, University of Dundee, UK
Eur J Gastroenterol Hepatol 15:41-7. 2003.... - Activation of hepatic Nrf2 in vivo by acetaminophen in CD-1 miceChristopher E P Goldring
Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, Merseyside, UK
Hepatology 39:1267-76. 2004..In conclusion, GSH depletion alone is insufficient for Nrf2 activation: a more direct interaction is required, possibly involving chemical modification of Nrf2 or Keap1, which is facilitated by the prior loss of GSH... - Evolutionary conserved N-terminal domain of Nrf2 is essential for the Keap1-mediated degradation of the protein by proteasomeYasutake Katoh
Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8577, Japan
Arch Biochem Biophys 433:342-50. 2005..These results thus demonstrate that DLG motif plays essential roles in the Keap1-mediated proteasomal degradation of Nrf2 in the cytoplasm... - Deficiency of glutathione transferase zeta causes oxidative stress and activation of antioxidant response pathwaysAnneke C Blackburn
Division of Molecular Bioscience, John Curtin School of Medical Research, Australian National University, Canberra
Mol Pharmacol 69:650-7. 2006..Patients with acquired deficiency of GSTZ1-1 caused by therapeutic exposure to dichloroacetic acid for the clinical treatment of lactic acidosis may be at increased risk of drug- and chemical-induced toxicity... - Characterization of the rat aflatoxin B1 aldehyde reductase gene, AKR7A1. Structure and chromosomal localization of AKR7A1 as well as identification of antioxidant response elements in the gene promoterElizabeth M Ellis
Department of Bioscience and Pharmaceutical Sciences, University of Strathclyde, Glasgow G1 1XW, UK
Carcinogenesis 24:727-37. 2003..Between nucleotides -810 and -106 bp from the TSS 16 ARE-related sequences were identified. Four of these putative enhancers lay between -389 and -355 bp, and the motif 5'-GAGTGAG-3' was repeated three times within the 35 bp region... - Reduction in antioxidant defenses may contribute to ochratoxin A toxicity and carcinogenicityChristophe Cavin
Quality and Safety Department, Nestle Research Center, CH 1000 Lausanne 26, Switzerland
Toxicol Sci 96:30-9. 2007..Our data suggest that reduction of cellular defense against oxidative stress by Nrf2 inhibition may be a plausible mechanism of OTA nephrotoxicity and carcinogenicity... - The hepatotoxic metabolite of acetaminophen directly activates the Keap1-Nrf2 cell defense systemIan M Copple
Department of Pharmacology and Therapeutics, School of Biomedical Sciences, The University of Liverpool, Liverpool, UK
Hepatology 48:1292-301. 2008..It is possible that both of these mechanisms contribute to the activation of Nrf2 by acetaminophen... - Nomenclature for mammalian soluble glutathione transferasesBengt Mannervik
Department of Biochemistry, Uppsala University Biomedical Center, Sweden
Methods Enzymol 401:1-8. 2005..Soluble GSTs from other mammalian species can be classified in the same manner as the human enzymes, and this chapter presents the application of the nomenclature to the rat and mouse GSTs...