dihydrofolate reductase

Summary

Gene Symbol: dihydrofolate reductase
Description: dihydrofolate reductase
Alias: DHFRP1, DYR, dihydrofolate reductase
Species: human
Products:     dihydrofolate reductase

Top Publications

  1. Davies J, Delcamp T, Prendergast N, Ashford V, Freisheim J, Kraut J. Crystal structures of recombinant human dihydrofolate reductase complexed with folate and 5-deazafolate. Biochemistry. 1990;29:9467-79 pubmed
    The 2.3-A crystal structure of recombinant human dihydrofolate reductase (EC 1.5.1.3, DHFR) has been solved as a binary complex with folate (a poor substrate at neutral pH) and also as a binary complex with an inhibitor, 5-deazafolate...
  2. Chen M, Shimada T, Moulton A, Cline A, Humphries R, Maizel J, et al. The functional human dihydrofolate reductase gene. J Biol Chem. 1984;259:3933-43 pubmed
    ..cloning, mapping, and DNA sequencing techniques have been used to characterize the functional human dihydrofolate reductase (DHFR) gene. The gene is about 30 kilobases in length...
  3. Johnson W, Stenroos E, Spychala J, Chatkupt S, Ming S, Buyske S. New 19 bp deletion polymorphism in intron-1 of dihydrofolate reductase (DHFR): a risk factor for spina bifida acting in mothers during pregnancy?. Am J Med Genet A. 2004;124A:339-45 pubmed
    ..We recently discovered a polymorphic 19 bp deletion allele (frequency 0.45) within intron-1 of dihydrofolate reductase (DHFR) that is a good candidate for such a genetic factor...
  4. Parle McDermott A, Pangilinan F, Mills J, Kirke P, Gibney E, Troendle J, et al. The 19-bp deletion polymorphism in intron-1 of dihydrofolate reductase (DHFR) may decrease rather than increase risk for spina bifida in the Irish population. Am J Med Genet A. 2007;143A:1174-80 pubmed
    ..This has focused attention on folate-related genes such as dihydrofolate reductase (DHFR) in a bid to identify the genetic factors that influence NTD risk through either the fetal or ..
  5. Bhabha G, Tuttle L, Martinez Yamout M, Wright P. Identification of endogenous ligands bound to bacterially expressed human and E. coli dihydrofolate reductase by 2D NMR. FEBS Lett. 2011;585:3528-32 pubmed publisher
    b>Dihydrofolate reductase (DHFR) is a well-studied drug target and a paradigm for understanding enzyme catalysis...
  6. Liu C, Hanoian P, French J, Pringle T, Hammes Schiffer S, Benkovic S. Functional significance of evolving protein sequence in dihydrofolate reductase from bacteria to humans. Proc Natl Acad Sci U S A. 2013;110:10159-64 pubmed publisher
    ..Here we trace the evolution of dihydrofolate reductase (DHFR) and identify multiple key divergence sites among 233 species between humans and bacteria...
  7. Bhabha G, Ekiert D, Jennewein M, Zmasek C, Tuttle L, Kroon G, et al. Divergent evolution of protein conformational dynamics in dihydrofolate reductase. Nat Struct Mol Biol. 2013;20:1243-9 pubmed publisher
    ..We characterized the atomic-level motions across divergent members of the dihydrofolate reductase (DHFR) family...
  8. Kateera F, Nsobya S, Tukwasibwe S, Hakizimana E, Mutesa L, Mens P, et al. Molecular surveillance of Plasmodium falciparum drug resistance markers reveals partial recovery of chloroquine susceptibility but sustained sulfadoxine-pyrimethamine resistance at two sites of different malaria transmission intensities in Rwanda. Acta Trop. 2016;164:329-336 pubmed publisher
    ..Continued surveillance of P. falciparum CQ and SP associated polymorphisms is recommended for guiding future rational drug policy-making and mitigation of future risk of anti-malaria drug resistance development. ..
  9. Kong X, Li W, Guo L, Zhang J, Chen X, Liu W, et al. Sesamin enhances nitric oxide bioactivity in aortas of spontaneously hypertensive rats. Ther Adv Cardiovasc Dis. 2015;9:314-24 pubmed publisher
    ..The protein expression of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (P-eNOS), dihydrofolate reductase (DHFR), nicotinamide adenine dinucleotide phosphate oxidase subunit p47phox, and copper, zinc superoxide ..

More Information

Publications133 found, 100 shown here

  1. Roellig D, Savage M, Fujita A, Barnabé C, Tibayrenc M, Steurer F, et al. Genetic variation and exchange in Trypanosoma cruzi isolates from the United States. PLoS ONE. 2013;8:e56198 pubmed publisher
    ..exchange was obtained by comparing sequence phylogenies of nuclear and mitochondrial gene targets, dihydrofolate reductase-thymidylate synthase (DHFR-TS) and the cytochrome oxidase subunit II- NADH dehydrogenase subunit I region ..
  2. Skariyachan S, Mahajanakatti A, Grandhi N, Prasanna A, Sen B, Sharma N, et al. Environmental monitoring of bacterial contamination and antibiotic resistance patterns of the fecal coliforms isolated from Cauvery River, a major drinking water source in Karnataka, India. Environ Monit Assess. 2015;187:279 pubmed publisher
    ..This is probably the first study elucidating the bacterial pollution and antibiotic sensitivity profiling of fecal coliforms isolated from River Cauvery, Karnataka, India. ..
  3. Ravella K, Al Hendy A, Sharan C, Hale A, Channon K, Srinivasan S, et al. Chronic estrogen deficiency causes gastroparesis by altering neuronal nitric oxide synthase function. Dig Dis Sci. 2013;58:1507-15 pubmed publisher
    ..We conclude that chronic estrogen deficiency negatively modifies the function of both BH4 and nNOS thereby contributing to the development of gastroparesis in a FORKO mouse model. ..
  4. Semmler A, Heese P, Stoffel Wagner B, Muschler M, Heberlein A, Bigler L, et al. Alcohol abuse and cigarette smoking are associated with global DNA hypermethylation: results from the German Investigation on Neurobiology in Alcoholism (GINA). Alcohol. 2015;49:97-101 pubmed publisher
    ..This suggests a direct effect of alcohol consumption and smoking on DNA methylation, which is not mediated by effects of alcohol on homocysteine metabolism. ..
  5. Delinasios J, Angeli F, Koumakis G, Kumar S, Kang W, Sica G, et al. Proliferating fibroblasts and HeLa cells co-cultured in vitro reciprocally influence growth patterns, protein expression, chromatin features and cell survival. Anticancer Res. 2015;35:1881-916 pubmed
    ..with dyes such as Giemsa and silver staining, with immunochemistry for Ki-67 and E-cadherin, with dihydrofolate reductase (DHFR) enzyme reaction, as well as live cell staining for non-specific esterases and lipids...
  6. He M, Yao K, Shi W, Gao W, Yuan L, Yu S, et al. Dynamics of serotype 14 Streptococcus pneumoniae population causing acute respiratory infections among children in China (1997-2012). BMC Infect Dis. 2015;15:266 pubmed publisher
    ..macrolides resistance genes ermB and mefA, as well as the sulfamethoxazole-trimethoprim resistance gene dihydrofolate reductase (DHFR) were detected by polymerase chain reaction (PCR)...
  7. Sastu U, Abdullah N, Norahmad N, Saat M, Muniandy P, Jelip J, et al. Mutations of pvdhfr and pvdhps genes in vivax endemic-malaria areas in Kota Marudu and Kalabakan, Sabah. Malar J. 2016;15:63 pubmed publisher
    ..Point mutations in the genes that encode the two enzymes involved in the folate biosynthesis pathway, dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) enzymes confer resistance to pyrimethamine and sulfadoxine ..
  8. Barnadas C, Timinao L, Javati S, Iga J, Malau E, Koepfli C, et al. Significant geographical differences in prevalence of mutations associated with Plasmodium falciparum and Plasmodium vivax drug resistance in two regions from Papua New Guinea. Malar J. 2015;14:399 pubmed publisher
    ..the presence of mutations in chloroquine resistance transporter (crt), multidrug resistance 1 (mdr1), dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes in Plasmodium falciparum (n = 727) and Plasmodium vivax (..
  9. Bamaga O, Mahdy M, Lim Y. Frequencies distribution of dihydrofolate reductase and dihydropteroate synthetase mutant alleles associated with sulfadoxine-pyrimethamine resistance in Plasmodium falciparum population from Hadhramout Governorate, Yemen. Malar J. 2015;14:516 pubmed publisher
    ..This study aimed to screen mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) genes associated with SP resistance among P...
  10. Oyebola K, Aina O, Idowu E, Olukosi Y, Ajibaye O, Otubanjo O, et al. A barcode of multilocus nuclear DNA identifies genetic relatedness in pre- and post-Artemether/Lumefantrine treated Plasmodium falciparum in Nigeria. BMC Infect Dis. 2018;18:392 pubmed publisher
    ..gene (crt-76), multidrug resistance genes (mdr1-86 and mdr1-184), dihydropteroate synthase (dhps-540), dihydrofolate reductase (dhfr-108) and kelch domain (K-13580) were genotyped by high resolution melt analysis of polymerase chain ..
  11. Huang B, Huang S, Su X, Tong X, Yan J, Li H, et al. Molecular surveillance of pvdhfr, pvdhps, and pvmdr-1 mutations in Plasmodium vivax isolates from Yunnan and Anhui provinces of China. Malar J. 2014;13:346 pubmed publisher
    ..Analysis of dihydrofolate reductase (dhfr), dihydropteroate synthase (dhps), and multidrug resistance (mdr-1) gene mutations in P...
  12. Adeel A, Elnour F, Elmardi K, Abd Elmajid M, Elhelo M, Ali M, et al. High efficacy of artemether-lumefantrine and declining efficacy of artesunate + sulfadoxine-pyrimethamine against Plasmodium falciparum in Sudan (2010-2015): evidence from in vivo and molecular marker studies. Malar J. 2016;15:285 pubmed publisher
    ..The frequency distribution of molecular markers for antifolate resistance in dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes was studied in pre-treatment samples in four sites in ..
  13. Oyebola K, Idowu E, Olukosi Y, Awolola T, Amambua Ngwa A. Pooled-DNA sequencing identifies genomic regions of selection in Nigerian isolates of Plasmodium falciparum. Parasit Vectors. 2017;10:320 pubmed publisher
    ..There was a weak signature of selection in the dihydrofolate reductase (DHFR) gene on chromosome 4 and MDR5 genes on chromosome 13, with only 2 and 3 SNPs respectively ..
  14. Zhou C, Zhu X, Elsheikha H, He S, Li Q, Zhou D, et al. Global iTRAQ-based proteomic profiling of Toxoplasma gondii oocysts during sporulation. J Proteomics. 2016;148:12-9 pubmed publisher
    ..ACL), GMP synthase, IMP dehydrogenase (IMPDH), poly (ADP-ribose) glycohydrolase (PARG), and bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS) as the top five hubs...
  15. Shiao S, Grayson J, Lie A, Yu C. Personalized Nutrition-Genes, Diet, and Related Interactive Parameters as Predictors of Cancer in Multiethnic Colorectal Cancer Families. Nutrients. 2018;10: pubmed publisher
    ..synthase (MTR) 2756, methionine synthase reductase (MTRR 66), and dihydrofolate reductase (DHFR) 19bp, and they were used to compute a total gene mutation score...
  16. Wong L, Flibotte S, Sinha S, Chiang J, Giaever G, Nislow C. Genome-Wide Screen Reveals sec21 Mutants of Saccharomyces cerevisiae Are Methotrexate-Resistant. G3 (Bethesda). 2017;7:1251-1257 pubmed publisher
    ..Known methotrexate resistance mechanisms include mutations that increase expression of the dihydrofolate reductase (DHFR) target as well as those that maintain function yet reduce the drug's binding affinity...
  17. Bansal D, Acharya A, Bharti P, Abdelraheem M, Elmalik A, Abosalah S, et al. Distribution of Mutations Associated with Antifolate and Chloroquine Resistance among Imported Plasmodium vivax in the State of Qatar. Am J Trop Med Hyg. 2017;: pubmed publisher
    ..vivax malaria. The present study examined the prevalence of mutations in dihydrofolate reductase (dhfr), dihydropteroate synthase (dhps) genes and CQ resistance transporter (crt-o) ..
  18. Syafruddin D, Asih P, Casey G, Maguire J, Baird J, Nagesha H, et al. Molecular epidemiology of Plasmodium falciparum resistance to antimalarial drugs in Indonesia. Am J Trop Med Hyg. 2005;72:174-81 pubmed
    ..20-50 patients was collected at each site, DNA was isolated, and the sequences of four different genes (dihydrofolate reductase [dhfr], dihydropteroate synthase [dhps], P. falciparum multidrug resistance 1 [pfmdr1], and P...
  19. Chaabane S, Marzouk S, Akrout R, Ben Hamad M, Achour Y, Rebai A, et al. Genetic Determinants of Methotrexate Toxicity in Tunisian Patients with Rheumatoid Arthritis: A Study of Polymorphisms Involved in the MTX Metabolic Pathway. Eur J Drug Metab Pharmacokinet. 2016;41:385-93 pubmed publisher
    ..Genotyping of 5,10 methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), dihydrofolate reductase (DHFR 19-base pair deletion allele), thymidylate synthase (TYMS 2R/3R), methionine synthase (MTR A2756G) ..
  20. Xie X, Zhang Z, Wang X, Luo Z, Lai B, Xiao L, et al. Stachydrine protects eNOS uncoupling and ameliorates endothelial dysfunction induced by homocysteine. Mol Med. 2018;24:10 pubmed publisher
    ..GTP cyclohydrolase 1 (GTPCH1) and dihydrofolate reductase (DHFR) expressions were measured by using quantitative reverse transcriptase-PCR (qRT-PCR) and Western ..
  21. Kamynina E, Lachenauer E, DiRisio A, Liebenthal R, Field M, Stover P. Arsenic trioxide targets MTHFD1 and SUMO-dependent nuclear de novo thymidylate biosynthesis. Proc Natl Acad Sci U S A. 2017;114:E2319-E2326 pubmed publisher
    ..to the nucleus during S-phase, where they form a multienzyme complex with thymidylate synthase (TYMS) and dihydrofolate reductase (DHFR), as well as the components of the DNA replication machinery...
  22. Mohapatra P, Sarma D, Prakash A, Bora K, Ahmed M, Sarma B, et al. Molecular evidence of increased resistance to anti-folate drugs in Plasmodium falciparum in North-East India: a signal for potential failure of artemisinin plus sulphadoxine-pyrimethamine combination therapy. PLoS ONE. 2014;9:e105562 pubmed publisher
    ..Associations between resistant haplotypes and the clinical outcomes and emerging resistance in sulphadoxine/pyrimethamine in relation to the efficacy of the currently used artemisinin combination therapy are discussed. ..
  23. Talundzic E, Ravishankar S, Kelley J, Patel D, Pluciński M, Schmedes S, et al. Next-Generation Sequencing and Bioinformatics Protocol for Malaria Drug Resistance Marker Surveillance. Antimicrob Agents Chemother. 2018;62: pubmed publisher
    ..Our goal is to implement MaRS at the CDC for routine surveillance of imported malaria cases in the United States and to aid in the adoption of this system at participating state public health laboratories, as well as by global partners. ..
  24. Esu E, Tacoli C, Gai P, Berens Riha N, Pritsch M, Loescher T, et al. Prevalence of the Pfdhfr and Pfdhps mutations among asymptomatic pregnant women in Southeast Nigeria. Parasitol Res. 2018;117:801-807 pubmed publisher
    ..The continuous monitoring of SP molecular markers of resistance is required to assess thresholds. The evaluation of alternative preventive treatment strategies and drug options for preventing malaria in pregnancy may be necessary. ..
  25. Yang S, Choi S, Lee J, Park A, Wang K, Phi J, et al. miR-192 suppresses leptomeningeal dissemination of medulloblastoma by modulating cell proliferation and anchoring through the regulation of DHFR, integrins, and CD47. Oncotarget. 2015;6:43712-30 pubmed publisher
    ..05). Medulloblastoma with seeding showed specific DEmiRs compared with those without. miR-192 suppresses leptomeningeal dissemination of medulloblastoma by modulating cell proliferation and anchoring ability. ..
  26. Ruizendaal E, Tahita M, Traore Coulibaly M, Tinto H, Schallig H, Mens P. Presence of quintuple dhfr N51, C59, S108 - dhps A437, K540 mutations in Plasmodium falciparum isolates from pregnant women and the general population in Nanoro, Burkina Faso. Mol Biochem Parasitol. 2017;217:13-15 pubmed publisher
    ..Close surveillance of SP resistance mutations is therefore warranted. ..
  27. Horst R, Fenton W, Englander S, Wuthrich K, Horwich A. Folding trajectories of human dihydrofolate reductase inside the GroEL GroES chaperonin cavity and free in solution. Proc Natl Acad Sci U S A. 2007;104:20788-92 pubmed
    ..by using NMR measurements of the time course of acquisition of amide proton exchange protection of human dihydrofolate reductase (DHFR) during folding in the presence of methotrexate and ATP either free in solution or inside the ..
  28. Whitsett J, Rangel Filho A, Sethumadhavan S, Celinska J, WIDLANSKY M, Vasquez Vivar J. Human endothelial dihydrofolate reductase low activity limits vascular tetrahydrobiopterin recycling. Free Radic Biol Med. 2013;63:143-50 pubmed publisher
    ..One of the oxidation products of BH?, 7,8-dihydrobiopterin (7,8-BH?), is recycled back to BH? by dihydrofolate reductase (DHFR)...
  29. Jabeen S, Holmboe L, Alnæs G, Andersen A, Hall K, Kristensen V. Impact of genetic variants of RFC1, DHFR and MTHFR in osteosarcoma patients treated with high-dose methotrexate. Pharmacogenomics J. 2015;15:385-90 pubmed publisher
    ..029). Also patients homozygous for the G allele of rs1053129 in the dihydrofolate reductase (DHFR) gene were more likely to have a metastasis (45%, P= 0...
  30. Bourne C. Utility of the Biosynthetic Folate Pathway for Targets in Antimicrobial Discovery. Antibiotics (Basel). 2014;3:1-28 pubmed publisher
    ..pathway leads to synthesis of required precursors for cellular function and contains a critical node, dihydrofolate reductase (DHFR), which is shared between prokaryotes and eukaryotes...
  31. Li P, Zhao Z, Xing H, Li W, Zhu X, Cao Y, et al. Plasmodium malariae and Plasmodium ovale infections in the China-Myanmar border area. Malar J. 2016;15:557 pubmed
    ..These minor parasite species displayed low levels of polymorphisms in the msp-1, dhfr and dhps genes. ..
  32. Moruzzi S, Udali S, Ruzzenente A, Guglielmi A, Guarini P, Martinelli N, et al. The RFC1 80G>A, among Common One-Carbon Polymorphisms, Relates to Survival Rate According to DNA Global Methylation in Primary Liver Cancers. PLoS ONE. 2016;11:e0167534 pubmed publisher
  33. Rudin S, Marable M, Huang R. The Promise of Pharmacogenomics in Reducing Toxicity During Acute Lymphoblastic Leukemia Maintenance Treatment. Genomics Proteomics Bioinformatics. 2017;15:82-93 pubmed publisher
    ..polymorphisms in genes encoding solute carrier organic anion transporter family member 1B1 (SLCO1B1) and dihydrofolate reductase (DHFR)...
  34. Guijon F, Greulich Bode K, Paraskevas M, Baker P, Mai S. Premalignant cervical lesions are characterized by dihydrofolate reductase gene amplification and c-Myc overexpression: possible biomarkers. J Low Genit Tract Dis. 2007;11:265-72 pubmed
    ..is associated with overall genomic instability and locus-specific genomic instability involving the dihydrofolate reductase (DHFR) locus...
  35. Sahu S, Ghosh S, Kalita J, Dutta M, Bhat H. Design, synthesis and antimalarial screening of some hybrid 4-aminoquinoline-triazine derivatives against pf-DHFR-TS. Exp Parasitol. 2016;163:38-45 pubmed publisher
    ..Synthesized compounds were characterised by FTIR, (1)H NMR, (13)C NMR, mass spectroscopy and were screened for antimalarial activity against 3D7 strain of Plasmodium falciparum. ..
  36. Rodrigues J, Bershtein S, Li A, Lozovsky E, Hartl D, Shakhnovich E. Biophysical principles predict fitness landscapes of drug resistance. Proc Natl Acad Sci U S A. 2016;113:E1470-8 pubmed publisher
    ..a predictive biophysics-based fitness landscape of trimethoprim (TMP) resistance for Escherichia coli dihydrofolate reductase (DHFR)...
  37. Perez Abraham R, Sanchez K, Alfonso M, Gubler U, Siekierka J, Goodey N. Expression, purification and enzymatic characterization of Brugia malayi dihydrofolate reductase. Protein Expr Purif. 2016;128:81-5 pubmed publisher
    ..Current literature suggests that dihydrofolate reductase is a potential drug target for the elimination of B. malayi...
  38. Alotaibi M, Reyes B, Le T, Luong P, Valafar F, Metzger R, et al. Structure-based analysis of Bacilli and plasmid dihydrofolate reductase evolution. J Mol Graph Model. 2017;71:135-153 pubmed publisher
    b>Dihydrofolate reductase (DHFR), a key enzyme in tetrahydrofolate-mediated biosynthetic pathways, has a structural motif known to be highly conserved over a wide range of organisms...
  39. Yeo J, Ho S, Mariati M, Koh E, Tay S, Woen S, et al. Optimized Selection Marker and CHO Host Cell Combinations for Generating High Monoclonal Antibody Producing Cell Lines. Biotechnol J. 2017;: pubmed publisher
    ..with different strengths, the expression of five antibiotics resistance genes (ARGs) in CHO-K1 cells and dihydrofolate reductase (DHFR) in CHO DG44 cells is optimized to enhance the stringency of selection for high producing cells...
  40. Ceppi F, Gagné V, Douyon L, Quintin C, Colombini A, Parasole R, et al. DNA variants in DHFR gene and response to treatment in children with childhood B ALL: revisited in AIEOP-BFM protocol. Pharmacogenomics. 2017;: pubmed publisher
    We have previously reported an association of dihydrofolate reductase promoter polymorphisms with reduced event-free survival in childhood acute lymphoblastic leukemia (ALL) patients treated with Dana Farber Cancer Institute protocol...
  41. Gemmati D, De Mattei M, Catozzi L, Della Porta M, Serino M, Ambrosio C, et al. DHFR 19-bp insertion/deletion polymorphism and MTHFR C677T in adult acute lymphoblastic leukaemia: is the risk reduction due to intracellular folate unbalancing?. Am J Hematol. 2009;84:526-9 pubmed publisher
  42. Talawanich Y, Kamchonwongpaisan S, Sirawaraporn W, Yuthavong Y. Use of bacterial surrogates as a tool to explore antimalarial drug interaction: Synergism between inhibitors of malarial dihydrofolate reductase and dihydropteroate synthase. Acta Trop. 2015;149:64-9 pubmed publisher
    ..Inhibitors of dihydrofolate reductase (DHFR) such as pyrimethamine and of dihydropteroate synthase (DHPS) such as sulfa drugs are known to have ..
  43. Cai Z, Lu Q, Ding Y, Wang Q, Xiao L, Song P, et al. Endothelial Nitric Oxide Synthase-Derived Nitric Oxide Prevents Dihydrofolate Reductase Degradation via Promoting S-Nitrosylation. Arterioscler Thromb Vasc Biol. 2015;35:2366-73 pubmed publisher
    b>Dihydrofolate reductase (DHFR) is a key protein involved in tetrahydrobiopterin (BH4) regeneration from 7,8-dihydrobiopterin (BH2)...
  44. Singh Y, Mirdha B, Guleria R, Khalil S, Panda A, Chaudhry R, et al. Molecular detection of DHFR gene polymorphisms in Pneumocystis jirovecii isolates from Indian patients. J Infect Dev Ctries. 2015;9:1250-6 pubmed publisher
    ..TMP-SMX) combination is commonly used for the treatment of PCP, targeting both dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) enzymes...
  45. Walter R, Mairinger F, Werner R, Vollbrecht C, Hager T, Schmid K, et al. Folic-acid metabolism and DNA-repair phenotypes differ between neuroendocrine lung tumors and associate with aggressive subtypes, therapy resistance and outcome. Oncotarget. 2016;7:20166-79 pubmed publisher
  46. Ritter A, Rauschert T, Oertli M, Piehlmaier D, Mantas P, Kuntzelmann G, et al. Disruption of the gene C12orf35 leads to increased productivities in recombinant CHO cell lines. Biotechnol Bioeng. 2016;113:2433-42 pubmed publisher
    ..are mediated by increased levels of mRNA of the exogenes heavy chain (HC) and light chain (LC) as well as dihydrofolate reductase (DHFR) and neomycin phosphotransferase (Neo) during the stable expression of antibodies. Biotechnol...
  47. Lourens A, Gravestock D, van Zyl R, Hoppe H, Kolesnikova N, Taweechai S, et al. Design, synthesis and biological evaluation of 6-aryl-1,6-dihydro-1,3,5-triazine-2,4-diamines as antiplasmodial antifolates. Org Biomol Chem. 2016;14:7899-911 pubmed publisher
    ..66 nM). The compounds were not toxic to mammalian cells at therapeutic concentrations and were shown to be inhibitors of parasitic DHFR in a biochemical enzyme assay. ..
  48. Skacel N, Menon L, Mishra P, Peters R, Banerjee D, Bertino J, et al. Identification of amino acids required for the functional up-regulation of human dihydrofolate reductase protein in response to antifolate Treatment. J Biol Chem. 2005;280:22721-31 pubmed
    Human dihydrofolate reductase (DHFR) protein levels rapidly increase upon exposure to methotrexate, a potent inhibitor of this enzyme...
  49. Koomdee N, Hongeng S, Apibal S, Pakakasama S. Association between polymorphisms of dihydrofolate reductase and gamma glutamyl hydrolase genes and toxicity of high dose methotrexate in children with acute lymphoblastic leukemia. Asian Pac J Cancer Prev. 2012;13:3461-4 pubmed
    ..Single nucleotide polymorphisms (SNPs) of dihydrofolate reductase (DHFR) and gamma glutamyl hydrolase (GGH) are known to alter their enzymatic activity and thus affect the ..
  50. Ozaki M, Molloy A, Mills J, Fan R, Wang Y, Gibney E, et al. The Dihydrofolate Reductase 19 bp Polymorphism Is Not Associated with Biomarkers of Folate Status in Healthy Young Adults, Irrespective of Folic Acid Intake. J Nutr. 2015;145:2207-11 pubmed publisher
    b>Dihydrofolate reductase (DHFR) is essential for the conversion of folic acid to active folate needed for one-carbon metabolism...
  51. Bueno O, Molloy A, Fernandez Ballart J, García Minguillán C, Ceruelo S, Ríos L, et al. Common Polymorphisms That Affect Folate Transport or Metabolism Modify the Effect of the MTHFR 677C > T Polymorphism on Folate Status. J Nutr. 2016;146:1-8 pubmed publisher
    ..cyclohydrolase-10-formyltetrahydrofolate synthetase (MTHFD1) 1958G > A, MTHFD1 -105C > T, dihydrofolate reductase (DHFR) 19-bp insertion/deletion, and solute carrier family 19A, member 1 (SLC19A1) 80G > A ..
  52. Stefanova V, Yartseva N, Petrov A. [COMPARATIVE CYTOGENETIC ANALYSIS OF MONOLAYER AND SUSPENSION CHINESE HAMSTER OVARY CELL LINES CHO(dhfr-)]. Tsitologiia. 2015;57:491-8 pubmed
    ..Necessity of simultaneous GTG and FISH analysis of chromosomes rearrangements in the CHO cell lines under study is discussed. ..
  53. Alker A, Kazadi W, Kutelemeni A, Bloland P, Tshefu A, Meshnick S. dhfr and dhps genotype and sulfadoxine-pyrimethamine treatment failure in children with falciparum malaria in the Democratic Republic of Congo. Trop Med Int Health. 2008;13:1384-91 pubmed publisher
    ..Dhps-437 and dhps-540 are strongly associated with SP treatment failure and should be evaluated further as a method for surveillance of SP-based therapy in DRC. ..
  54. Chin C, Chin H, Chin C, Lai E, Ng S. Engineering selection stringency on expression vector for the production of recombinant human alpha1-antitrypsin using Chinese Hamster ovary cells. BMC Biotechnol. 2015;15:44 pubmed publisher
    ..Destabilization of dihydrofolate reductase (dhfr) selection marker by addition of AU-rich elements and murine ornithine decarboxylase PEST region ..
  55. Betts Z, Dickson A. Assessment of UCOE on Recombinant EPO Production and Expression Stability in Amplified Chinese Hamster Ovary Cells. Mol Biotechnol. 2015;57:846-58 pubmed publisher
    ..The data suggested that enhanced cell line recovery by transcriptional enhancement of selection markers, such as DHFR, could be achieved. ..
  56. Srinivasan B, Tonddast Navaei S, Skolnick J. Ligand binding studies, preliminary structure-activity relationship and detailed mechanistic characterization of 1-phenyl-6,6-dimethyl-1,3,5-triazine-2,4-diamine derivatives as inhibitors of Escherichia coli dihydrofolate reductase. Eur J Med Chem. 2015;103:600-14 pubmed publisher
    ..This is the first comprehensive study on the binding and inhibition brought about by diaminotriazines of a gram-negative prokaryotic enzyme and provides valuable insights into the SAR as an aid to the discovery of novel antibiotics. ..
  57. Qi Z, Wilkinson M, Chen X, Sankararaman S, Mayhew D, Mitra R. An optimized, broadly applicable piggyBac transposon induction system. Nucleic Acids Res. 2017;45:e55 pubmed publisher
    ..We believe the FKBP-based PB transposon induction will be useful for transposon-mediated genome engineering, insertional mutagenesis and the genome-wide mapping of transcription factor binding. ..
  58. Abdizadeh H, Tamer Y, Acar O, Toprak E, Atilgan A, Atilgan C. Increased substrate affinity in the Escherichia coli L28R dihydrofolate reductase mutant causes trimethoprim resistance. Phys Chem Chem Phys. 2017;19:11416-11428 pubmed publisher
    b>Dihydrofolate reductase (DHFR) is a ubiquitous enzyme with an essential role in cell metabolism. DHFR catalyzes the reduction of dihydrofolate to tetrahydrofolate, which is a precursor for purine and thymidylate synthesis...
  59. Moree B, Connell K, Mortensen R, Liu C, Benkovic S, SALAFSKY J. Protein Conformational Changes Are Detected and Resolved Site Specifically by Second-Harmonic Generation. Biophys J. 2015;109:806-15 pubmed publisher
    ..proteins labeled at lysine residues: calmodulin (CaM), maltose-binding protein (MBP), and dihydrofolate reductase (DHFR)...
  60. Chalupsky K, Kračun D, Kanchev I, Bertram K, Görlach A. Folic Acid Promotes Recycling of Tetrahydrobiopterin and Protects Against Hypoxia-Induced Pulmonary Hypertension by Recoupling Endothelial Nitric Oxide Synthase. Antioxid Redox Signal. 2015;23:1076-91 pubmed publisher
    ..b>Dihydrofolate reductase (DHFR) can recycle BH2 to BH4, leading to eNOS recoupling...
  61. Das S, Banik A, Hati A, Roy S. Low prevalence of dihydro folate reductase (dhfr) and dihydropteroate synthase (dhps) quadruple and quintuple mutant alleles associated with SP resistance in Plasmodium vivax isolates of West Bengal, India. Malar J. 2016;15:395 pubmed publisher
    ..infection by means of genetic polymorphisms, especially analysing the single nucleotide polymorphisms of dihydrofolate reductase (pvdhfr) and dihydropteroate synthase (pvdhps) gene among the field isolates of urban Kolkata Municipal ..
  62. Maurya S, Khan S, Bahuguna A, Kumar D, Rawat D. Synthesis, antimalarial activity, heme binding and docking studies of N-substituted 4-aminoquinoline-pyrimidine molecular hybrids. Eur J Med Chem. 2017;129:175-185 pubmed publisher
    ..The pharmacokinetic property analysis of best active compounds was also studied by ADMET prediction. ..
  63. Patel T, Vanparia S, Patel U, Dixit R, Chudasama C, Patel B, et al. Novel 2,3-disubstituted quinazoline-4(3H)-one molecules derived from amino acid linked sulphonamide as a potent malarial antifolates for DHFR inhibition. Eur J Med Chem. 2017;129:251-265 pubmed publisher
    ..against alleged receptor Pf-DHFR computationally as well as in vitro, proving their candidature as lead dihydrofolate reductase inhibitors...
  64. Rashid U, Ahmad W, Hassan S, Qureshi N, Niaz B, Muhammad B, et al. Design, synthesis, antibacterial activity and docking study of some new trimethoprim derivatives. Bioorg Med Chem Lett. 2016;26:5749-5753 pubmed publisher
    ..We further performed exploratory docking studies on dihydrofolate reductase (DHFR) to rationalize the in vitro biological data and to demonstrate the mechanism of antibacterial ..
  65. Tsushima M, Sato S, Nakamura H. Selective purification and chemical labeling of a target protein on ruthenium photocatalyst-functionalized affinity beads. Chem Commun (Camb). 2017;53:4838-4841 pubmed publisher
    ..b>Dihydrofolate reductase (DHFR) endogenously expressed in HeLa cells was detected by chemical labeling with biotin-TRT on the ..
  66. Giletti A, Vital M, Lorenzo M, Cardozo P, Borelli G, Gabus R, et al. Methotrexate pharmacogenetics in Uruguayan adults with hematological malignant diseases. Eur J Pharm Sci. 2017;109:480-485 pubmed publisher
    ..Besides, genotype distribution showed to be different from other populations, reinforcing the idea that genotype data from other populations should not be extrapolated to ours. ..
  67. Thakkar S, Thakor P, Doshi H, Ray A. 1,2,4-Triazole and 1,3,4-oxadiazole analogues: Synthesis, MO studies, in silico molecular docking studies, antimalarial as DHFR inhibitor and antimicrobial activities. Bioorg Med Chem. 2017;25:4064-4075 pubmed publisher
    ..The active compounds were further evaluated for enzyme inhibition efficacy against the receptor Pf-DHFR computationally as well as in vitro to prove their candidature as lead dihydrofolate reductase inhibitors.
  68. Tian Z, Xu D, Wang T, Wang X, Xu H, Zhao C, et al. Identification of a potent MAR element from the human genome and assessment of its activity in stably transfected CHO cells. J Cell Mol Med. 2017;: pubmed publisher
    ..In conclusion, the human CSP-B MAR element can improve transgene expression and its effects may be related to the NFAT and VIBP elements...
  69. Singh A, Deshpande N, Pramanik N, Jhunjhunwala S, Rangarajan A, Atreya H. Optimized peptide based inhibitors targeting the dihydrofolate reductase pathway in cancer. Sci Rep. 2018;8:3190 pubmed publisher
    We report the first peptide based hDHFR inhibitors designed on the basis of structural analysis of dihydrofolate reductase (DHFR)...
  70. van der Linden I, Nguyen U, Heil S, Franke B, Vloet S, Gellekink H, et al. Variation and expression of dihydrofolate reductase (DHFR) in relation to spina bifida. Mol Genet Metab. 2007;91:98-103 pubmed
    The dihydrofolate reductase (DHFR) enzyme is important for folate availability, folate turnover and DNA synthesis...
  71. Matherly L, Taub J, Wong S, Simpson P, Ekizian R, Buck S, et al. Increased frequency of expression of elevated dihydrofolate reductase in T-cell versus B-precursor acute lymphoblastic leukemia in children. Blood. 1997;90:578-89 pubmed
    The relationships between dihydrofolate reductase (DHFR) levels or methotrexate membrane transport and acute lymphoblastic leukemia (ALL) immunophenotype were evaluated on 51 T-cell and 44 B-precursor ALL specimens from 90 pediatric ALL ..
  72. Leveson Gower D, Michnick S, Ling V. Detection of TAP family dimerizations by an in vivo assay in mammalian cells. Biochemistry. 2004;43:14257-64 pubmed
    ..To identify interactions within the human TAP family, we adapted the dihydrofolate reductase protein-fragment complementation assay (DHFR PCA) to half ABC transporters...
  73. Semmler A, Bao X, Cao G, Kohler W, Weller M, Aubourg P, et al. Genetic variants of methionine metabolism and X-ALD phenotype generation: results of a new study sample. J Neurol. 2009;256:1277-80 pubmed publisher
    ..Whereas the influence of other polymorphisms of methionine metabolism was not confirmed, the present study supports the previously made observation that the Tc2 genotype contributes to X-ALD phenotype generation. ..
  74. Summers C, Mitchell L, Stanislawska Sachadyn A, Baido S, Blair I, Von Feldt J, et al. Genetic and lifestyle variables associated with homocysteine concentrations and the distribution of folate derivatives in healthy premenopausal women. Birth Defects Res A Clin Mol Teratol. 2010;88:679-88 pubmed publisher
    ..In African American and Caucasian women, different factors are associated with folate/Hcy phenotypes and may contribute to race-specific differences in the risks of a range of pregnancy-related pathologies. ..
  75. Beltzer J, Spiess M. In vitro binding of the asialoglycoprotein receptor to the beta adaptin of plasma membrane coated vesicles. EMBO J. 1991;10:3735-42 pubmed
    ..The cytoplasmic domain of the ASGP receptor subunit H1 fused to dihydrofolate reductase competed for receptor binding to the 100 kDa polypeptide in the plasma membrane-type AP complexes (AP-2)...
  76. Toma H, Imada Y, Vannachone B, Miyagi M, Kobayashi J, Uechi G, et al. A molecular epidemiologic study of point mutations for pyrimethamine-sulfadoxine resistance of Plasmodium falciparum isolates from Lao PDR. Southeast Asian J Trop Med Public Health. 2005;36:602-4 pubmed
    ..PS) resistant falciparum malaria in Lao PDR, the frequency of point mutations in dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) genes of Plasmodium falciparum were examined in 50 blood ..
  77. Stanisławska Sachadyn A, Brown K, Mitchell L, Woodside J, Young I, Scott J, et al. An insertion/deletion polymorphism of the dihydrofolate reductase (DHFR) gene is associated with serum and red blood cell folate concentrations in women. Hum Genet. 2008;123:289-95 pubmed publisher
    ..b>Dihydrofolate reductase catalyzes the reduction of folic acid to dihydrofolate and thereafter to tetrahydrofolate...
  78. Ng X, Boyd L, Dufficy L, Naumovski N, Blades B, Travers C, et al. Folate nutritional genetics and risk for hypertension in an elderly population sample. J Nutrigenet Nutrigenomics. 2009;2:1-8 pubmed publisher
    ..Regressing diastolic blood pressure and 677C>T-MTHFR genotype showed significance (males; p = 0.032) and borderline significance (all subjects). Dietary folate and 677C>T-MTHFR genotype may modify blood pressure. ..
  79. Porter K, Basu A, Hubbard A, Bates M, Kalman D, Rey O, et al. Association of genetic variation in cystathionine-beta-synthase and arsenic metabolism. Environ Res. 2010;110:580-7 pubmed publisher
    ..MTHFR), methionine synthase (MTR), cystathionine-beta-synthase (CBS), thymidylate synthase (TYMS), dihydrofolate reductase (DHFR), serine hydroxymethyltransferase 1 (SHMT1)] and glutathione biosynthesis [glutathione-S-..
  80. Marverti G, Ligabue A, Lombardi P, Ferrari S, Monti M, Frassineti C, et al. Modulation of the expression of folate cycle enzymes and polyamine metabolism by berberine in cisplatin-sensitive and -resistant human ovarian cancer cells. Int J Oncol. 2013;43:1269-80 pubmed publisher
    ..cells more than the sensitive counterparts, by interfering with the expression of folate cycle enzymes, dihydrofolate reductase (DHFR) and thymidylate synthase (TS)...
  81. Wang Y, Ha S, Zhang T, Kho D, Raz A, Xie Y. Polyubiquitylation of AMF requires cooperation between the gp78 and TRIM25 ubiquitin ligases. Oncotarget. 2014;5:2044-51 pubmed publisher
    ..This study uncovers a previously unknown functional link between gp78 and TRIM25 and provides mechanistic insight into gp78-mediated protein ubiquitylation...
  82. Chao B, Li B, Xiao X. Design, synthesis and evaluation of antitumor acylated monoaminopyrroloquinazolines. Bioorg Med Chem Lett. 2017;27:3107-3110 pubmed publisher
    ..N-1 primary amino group in 1,3-diaminopyrroloquinazoline is critical for its inhibitory activity against dihydrofolate reductase (DHFR)...
  83. Patel P, Bharti P, Bansal D, Ali N, Raman R, Mohapatra P, et al. Prevalence of mutations linked to antimalarial resistance in Plasmodium falciparum from Chhattisgarh, Central India: A malaria elimination point of view. Sci Rep. 2017;7:16690 pubmed publisher
    ..These findings provide potential information and understanding of the evolution and spread of different drug resistance alleles in Chhattisgarh. ..
  84. Vanguri V, Wang S, Godyna S, Ranganathan S, Liau G. Thrombospondin-1 binds to polyhistidine with high affinity and specificity. Biochem J. 2000;347:469-73 pubmed
    ..The possibility that other polyhistidine-containing proteins also interact with TSP1 warrants further study. ..
  85. Park K, Rue S, Lee I, Kim H, Lee I, Ahn J, et al. Modulation of Sp1-dependent transcription by a cis-acting E2F element in dhfr promoter. Biochem Biophys Res Commun. 2003;306:239-43 pubmed
    The dihydrofolate reductase (dhfr) promoter contains cis-acting elements for Sp1 and E2F. Here we examined the cooperative regulation of dhfr gene transcription by Sp1 and E2F in human osteosarcoma cells, U2OS...
  86. Craciun G, Tang Y, Feinberg M. Understanding bistability in complex enzyme-driven reaction networks. Proc Natl Acad Sci U S A. 2006;103:8697-702 pubmed
    ..Moreover, we indicate how switch-like behavior results from a well-studied mechanism for the action of human dihydrofolate reductase, an important anti-cancer target.
  87. Cam R, Eroglu A, Egin Y, Akar N. Dihydrofolate reductase (DHRF) 19-bp intron-1 deletion and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms in breast cancer. Breast Cancer Res Treat. 2009;115:431-2 pubmed publisher
  88. Semmler A, Linnebank M, Krex D, Götz A, Moskau S, Ziegler A, et al. Polymorphisms of homocysteine metabolism are associated with intracranial aneurysms. Cerebrovasc Dis. 2008;26:425-9 pubmed publisher
    ..677C-->T, MTHFR c.1298A-->C, cystathionine beta-synthase (CBS) c.844_855ins68, CBS c.833T-->C, dihydrofolate reductase (DHFR) c.594 + 59del19bp, glutathione S-transferase Omega-1 (GSTO1) c...
  89. Yuan T, Huang Y, Zhou C, Yu Y, Wang L, Zhuang H, et al. Nuclear translocation of dihydrofolate reductase is not a pre-requisite for DNA damage induced apoptosis. Apoptosis. 2009;14:699-710 pubmed publisher
    b>Dihydrofolate reductase (DHFR) is a key enzyme for the synthesis of thymidylate, and therefore, of DNA...
  90. Cario H, Smith D, Blom H, Blau N, Bode H, Holzmann K, et al. Dihydrofolate reductase deficiency due to a homozygous DHFR mutation causes megaloblastic anemia and cerebral folate deficiency leading to severe neurologic disease. Am J Hum Genet. 2011;88:226-31 pubmed publisher
    ..Genome-wide homozygosity mapping revealed a candidate region on chromosome 5 including the dihydrofolate reductase (DHFR) locus. DHFR sequencing revealed a homozygous DHFR mutation, c.458A>T (p...
  91. Dutta S, Shaw J, Chatterjee A, Sarkar K, Usha R, Chatterjee A, et al. Importance of gene variants and co-factors of folate metabolic pathway in the etiology of idiopathic intellectual disability. Nutr Neurosci. 2011;14:202-9 pubmed publisher
    ..002). A strong correlation between rs1801394 'G' allele and micronucleus was also noticed. From the present investigation, a role of genetic polymorphisms and vitamin B6 levels could be hypothesized in the etiology of IID. ..
  92. Lee S, Chen T, Lin L, Li C, Chen L, Hsing C, et al. Overexpression of thymidylate synthetase confers an independent prognostic indicator in nasopharyngeal carcinoma. Exp Mol Pathol. 2013;95:83-90 pubmed publisher
    Data mining on public domain identified that thymidylate synthetase (TYMS) and dihydrofolate reductase (DHFR) transcripts were significantly higher expressed in nasopharyngeal carcinoma (NPC)...