• Impairment of thymidylate (dTMP) biosynthesis severely diminishes the viability of parasitic protozoa and the absence of enzymatic activities specifically involved in the formation of dTMP (e.g. dUTPase, thymidylate synthase, dihydrofolate reductase or thymidine kinase) results in decreased deoxythymidine triphosphate (dTTP) levels and the so-called thymineless death. (eurekaselect.com)
  • Folic acid is a purely synthetic compound which must first be converted to tetrahydrofolate, or THF, by being cycled twice through the enzyme dihydrofolate reductase, or DHFR, to be utilized in methylation. (elpasobackclinic.com)
  • MR4), which contains Toxoplasma gondii dihydrofolate reductase-thymidylate synthase (Tgdhfr/ts) and green fluorescent protein gene (gfp) expression cassettes for pyrimethamine (PYR) selection and fluorescence detection of transfected parasites. (pberghei.eu)
  • dTMP kinase) catalyzes the phosphorylation of thymidine 5'-monophosphate (dTMP) to form thymidine 5'-diphosphate (dTDP) in the presence of ATP and magnesium: ATP + thymidine 5'-phosphate ⇌ {\displaystyle \rightleftharpoons } ADP + thymidine 5'-diphosphate Thymidylate kinase is a ubiquitous enzyme of about 25 Kd and is important in the dTTP synthesis pathway for DNA synthesis. (wikipedia.org)
  • Thymidylate synthase is vital for de novo DNA synthesis, by catalyzing the transformation of deoxy-uridine monophosphate (dUMP) to deoxy-thymidine monophosphate (dTMP). (careersfromscience.org)
  • We also constructed a thymidine producer by deleting the tdk gene and overexpressing the prs , ushA , thyA , dut , and ndk genes from Escherichia coli in strain BSK756, and the resulting strain BSK756T3 accumulated 151.2 mg/L thymidine, showing a 5.2-fold increase compared to the corresponding control strain. (biomedcentral.com)
  • By introducing specific gene modifications related to guanosine and thymidine accumulation, respectively, we demonstrated that genome-reduced strains had greatly improved properties compared to the wild-type strain as chassis cells for the production of these two products. (biomedcentral.com)
  • Thymidylate kinase's subfamily is predicted thymidylate kinase, TKRP1. (wikipedia.org)
  • Although less conserved, the earliest sporulation genes of sensory histidine kinases could not be positively assigned among 59 histidine kinase genes in the genome (Figure 8). (peptide-solubility.com)
  • Therefore, molecular docking was also used in the present study to simulate the binding of cordycepin with different antibacterial targets, such as β-ketoacyl-(acyl-carrier-protein) synthase III (FabH), DNA gyrase B and thymidylate kinase, in order to identify the most likely antimicrobial mechanism of cordycepin. (spandidos-publications.com)
  • Gefitinib and erlotinib would be effective for tumors with epidermal growth factor receptor (EGFR) mutations or increased EGFR gene copy numbers ( 6 ). (aacrjournals.org)
  • These possess included intratumoral degrees of thymidylate synthase (TS), TP53 mutations, microsatellite instability, and chromosomal deletions [6-8]. (careersfromscience.org)
  • Scope includes mutations and abnormal protein expression. (cancerindex.org)
  • Overlapping genes have been suggested to have multiple functions such as regulation of gene expression, translational coupling and genome overprinting - a process of generating novel genes through accumulated mutations inside a pre - existing gene 9, 10 . (ijpsr.com)
  • Vitamin B 6 and its derivative pyridoxal 5'-phosphate (PLP) are essential to over 100 enzymes mostly involved in protein metabolism . (oregonstate.edu)
  • The many biochemical reactions catalyzed by PLP-dependent enzymes are involved in essential biological processes, such as hemoglobin and amino acid biosynthesis, as well as fatty acid metabolism . (oregonstate.edu)
  • There are large differences between men and women of child-bearing age in the expression level of 5 key enzymes in one-carbon metabolism almost certainly caused by the sex hormones. (biomedcentral.com)
  • The ENO4 gene promoter comprised a CpG island and several TFBS, including AHR1 in the 5'-UTR region, which may suggest a role for ENO4 in aryl hydrocarbon ligand binding or metabolism. (edu.au)
  • Metabolic fitness relies on the functionality of heat shock proteins (HSPs), molecular chaperones that facilitate the correct folding of metabolism enzymes and their assembly in macromolecular structures. (biomedcentral.com)
  • Phenotypic classification classified tumors (either below or above the median expression level) with respect to the folic acid metabolism or DNA repair. (oncotarget.com)
  • Mycoplasmas have evolved from Gram-positive bacteria by reductive evolution thereby losing several genes involved in metabolism, cellular process and energy production 15, 16 . (ijpsr.com)
  • Pemetrexed disrupts the folate-dependant metabolic processes important for cell replication, inhibits the enzymes involved in folate metabolism and DNA synthesis, and inhibits protein synthesis. (medscape.com)
  • Results demonstrated that both strawberry extracts not only improved the lipid metabolism by decreasing triglycerides and LDL-cholesterol contents, but also improved the redox state of HepG2 cells by modulating thiobarbituric acid-reactive substances production, antioxidant enzyme activity and ROS generation. (edu.mx)
  • Amplification of DNA fragments of the chr3N and chr3C genes from pUCywrB_A plasmid was carried out by PCR with oligonucleotides designed to yield translational PhoA/LacZ fusions within hydrophilic loops of the Chr3N and Chr3C proteins, according to a topological model based on hydropathic profiles and secondary-structure prediction programs. (her2signaling.com)
  • enzymes or structural proteins are depicted. (peptide-solubility.com)
  • Thymidylate synthase (TYMS) enzyme is an anti-cancer target given its role in DNA biosynthesis. (bvsalud.org)
  • Studies to date indicate that high intratumoral levels of TS gene expression or TS protein generally predict for non-response, whereas low levels are associated with a high response rate. (imrpress.com)
  • Suicide genes code for enzymes, such as cytosine deaminase (CD), that convert non-toxic compounds (prodrugs) into toxic products. (invivogen.com)
  • The enzyme/prodrug strategy using cytosine deaminase (CD) and 5-fluorocytosine (5-FC) has been used for cancer gene therapy. (biomedcentral.com)
  • Serine hydroxymethyltransferase (SHMT), a pyridoxal phosphate-dependent enzyme, plays a vital role in the de novo pyrimidine biosynthesis pathway in malaria parasites. (pberghei.eu)
  • cMonkey integrates powerful de novo motif detection to identify conditionally co-regulated sets of genes. (systemsbiology.net)
  • A consequence of these allosteric interactions is that it is almost impossible to guess the effects of the up- or down-regulation of a particular enzyme. (biomedcentral.com)
  • The CDK family of enzymes orchestrate the regulation of key eukaryotic cellular processes. (cancer-research-network.com)
  • The heterodimer binds to vitamin D response element in target genes and leads to gene transcription regulation ( 1 ). (jcancer.org)
  • In addition, calcitriol has rapid effects that are independent of gene transcription regulation, which are defined as non-genomic effects and not mediated directly through steroid receptor-ligand-DNA interaction. (jcancer.org)
  • On the other hand, non-genomic actions may indirectly affect gene transcription via the regulation of intracellular signaling pathways that target transcription factors ( 3 ). (jcancer.org)
  • Recent advances in understanding the role that epigenetics plays in cancer pathogenesis and understanding the mechanisms through which these processes regulate gene expression have stimulated considerable interest in developing clinically viable antineoplastic agents that target enzymatic components of transcriptional regulatory complexes responsible for the establishment of pathologic epigenetic modifications that lead to deregulated gene expression in cancer. (aacrjournals.org)
  • Vertebrate ENOF1 (or ENO5) genes encode an antisense RNA, which may regulate mitochondrial thymidylate synthase activity that contained 12-15 coding exons. (edu.au)
  • The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway evaluation suggested that furthermore to Wnt and changing growth aspect (TGF) signaling pathways, that have been reported in response to follicle formation broadly, another mixed band of signaling pathways that regulate lipid synthesis and fat burning capacity, like the phosphatidylinositol signaling program and glycerolipid signaling and fat burning capacity, are Gemzar biological activity in charge of follicle formation also. (clinical-research-informatics.com)
  • Two most common SNPs of ERCC1 gene are C118T (rs11615) with a C → T substitution at exon 4 and C8092A (rs3212986) with a C→A change in the 3′-untranslated region, both of which have been speculated to regulate the ERCC1 mRNA expression and manage the NER pathway, consequently affecting the efficacy of platinum-based chemotherapy [ 7 ]. (hindawi.com)
  • Of note, PLP also functions as a coenzyme for glycogen phosphorylase, an enzyme that catalyzes the release of glucose from stored glycogen. (oregonstate.edu)
  • in particular, PLP is the cofactor for the enzyme kynureninase, which catalyzes the conversion of 3-hydroxykynurenine to 3-hydroxyanthranilic acid. (oregonstate.edu)
  • This enzyme catalyzes the transient breaking and rejoining of a single strand of DNA which allows the strands to pass through one another, thus altering the topology of DNA. (cancerindex.org)
  • Thymidylate synthase (TS) catalyzes the reductive methylation of deoxyuridine monophosphate (dUMP) by 5, 10-methylenetetrahydrofolate (CH2H4folate) to form deoxythymidine monophosphate (dTMP) and dihydrofolate (H2folate). (rcsb.org)
  • It has been reported that the genome-reduced Bacillus subtilis strain MBG874 showed clear advantages for the production of several heterologous enzymes including alkaline cellulase and protease. (biomedcentral.com)
  • Comparative ENO amino acid sequences and structures and ENO gene locations were examined using data from several vertebrate genome projects. (edu.au)
  • l -threonine production was increased 2.4-fold when the corresponding gene modifications were introduced into E. coli strain MGF-01 that has a 22 % genome reduction [ 12 ]. (biomedcentral.com)
  • The analyzed gene datasets were downloaded from the Gene Expression Omnibus and The Cancer Genome Atlas (TCGA) database. (cancerindex.org)
  • Overlapping genes in prokaryotes are a means to minimize genome size and increase the density of genetic information. (ijpsr.com)
  • Overlapping genes play an important role in genome reduction of Mycoplasmas during the course of their degenerative evolution. (ijpsr.com)
  • Gene pairs that occur as overlapping in both the genomes, gene pairs that occur as overlapping in one genome but are split in the other genome were separated out and more closely analysed. (ijpsr.com)
  • However, overlapping genes have been proposed as means of achieving genome reduction by retaining indispensable genes and compressing maximum amount of information in available sequence space 17 . (ijpsr.com)
  • As an endeavor to analyze the role of overlapping genes in genome reduction, in the present study all the overlapping genes in the genomes of the two obligatory human parasites, Mycoplasma hominis and Mycoplasma penetrans were systematically analyzed. (ijpsr.com)
  • The genes for the key σ factors (σH, σF, σE, σG, and σK) and the master regulator SpoOA were identified in the genome of DCB-2, and homologs for most of the sporulation genes were identified. (peptide-solubility.com)
  • Five such operons were identified in the genome of D. hafniense DCB-2 (Figure 8) including an octacistronic operon (Dhaf_0057-64) which encodes additional genes for Orn/Lys/Arg decarboxylase, DNA polymerase III δ' subunit, polymerase suppressor protein, and corrin/porphyrin methyltransferase, suggesting that the operon is used not only for the synthesis of a germinant receptor but for other metabolic activities in relation to sporulation/germination. (peptide-solubility.com)
  • A highly efficient non-viral process for programming mesenchymal stem cells for gene directed enzyme prodrug cancer therapy. (invivogen.com)
  • In mammalian cells, histone H3 Lys 9 (H3K9) methylation and histone hypoacetylation are usually associated with methylated DNA, heterochromatin, and gene silencing. (aacrjournals.org)
  • Histone hyperacetylation and H3K4 methylation are associated with unmethylated DNA, euchromatin, and gene expression ( Fig. 2 ). (aacrjournals.org)
  • In the mutant structures, ordered water or the other phosphate-binding arginines compensate for the hydrogen bonds made by Arg179 in the wild-type enzyme and there is almost no change in the conformation or binding site of dUMP. (rcsb.org)
  • We give a new explanation of the well known phenomenon that folate supplementation lowers homocysteine and we show how to use the model to investigate the effects of vitamin deficiencies, gene polymorphisms, and nutrient input changes. (biomedcentral.com)
  • Patients were genotyped for a panel of 192 tagging polymorphisms in 34 immune-related genes. (frontiersin.org)
  • Pharmacogenomics has been perceived as a useful tool to predict treatment response as well as clinical prognosis in cancer patients, and numerous studies have suggested the functions of single nucleotide polymorphisms (SNPs) in affecting drug sensitivity by modifying relevant genes [ 4 ]. (hindawi.com)
  • Consequently, it is necessary to identify functional gene polymorphisms as new biomarkers for accurately predicting clinical outcomes of chemotherapy in NSCLC, which could also reduce the side effects and provide the most cost-effective approach for individuals [ 3 , 4 ]. (hindawi.com)
  • This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. (cancerindex.org)
  • PLP functions as a coenzyme of 5-aminolevulinic acid synthase, which is involved in the synthesis of heme , an iron -containing component of hemoglobin . (oregonstate.edu)
  • DHF has been demonstrated to prevent thymidylate synthase and purine synthesis enzymes, which can affect DNA synthesis. (elpasobackclinic.com)
  • DHF is also believed to restrict the production of the MTHFR enzyme , which can lead to a decrease in methionine synthesis and homocysteine clearance. (elpasobackclinic.com)
  • This inhibits the formation of thymidylate and purines and arrests DNA, RNA, and protein synthesis. (medscape.com)
  • Cancer drugs such as 5-fluorouracil (5-FU) that target the enzyme thymidylate synthase (TS) have been and are still being widely used in cancer treatment, but as with other anti-cancer drugs, the majority of tumors do not respond to the treatment, whereas the patients still suffer drug-related toxicity. (imrpress.com)
  • We have evaluated the antitumor effect of combining IL-12 with CD gene transfer in mice bearing renal cell carcinoma (Renca) tumors. (biomedcentral.com)
  • UPRT fusion gene is provided in the expression plasmid pSelect-zeo which is selectable with Zeocin™ in mammalian and E. coli cells. (invivogen.com)
  • We investigated the clinical significance of E2F1 gene expression in relation to its target genes, thymidylate synthase ( TS ) and Survivin , in case of non-small-cell lung cancer (NSCLC). (aacrjournals.org)
  • XLS 97 kb) 12861_2017_153_MOESM8_ESM.xls (98K) GUID:?B2FE5241-0444-4D48-99D4-D5E55E4120EF Extra file 9: Desk S7: Target genes of the very best portrayed 18 miRNAs. (clinical-research-informatics.com)
  • Attempts to abolish toxicity in human patients while preserving potency against the target enzyme, have led to the development of ZD1694, which has already shown significant activity against colorectal tumours. (rcsb.org)
  • Thus, considerable interest was generated by data suggesting that the variable number of a 28 base-pair (bp) segment in the promoter region of the TS gene was associated with TS gene expression and/or protein expression, as well as with tumor response to 5-FU therapy, toxicity and patient survival. (imrpress.com)
  • Human ENO3 and ENO1 gene promoters also contained a diverse range of TFBS. (edu.au)
  • The main module page also shows the location of these motifs within the upstream sequences of the module member genes. (systemsbiology.net)
  • cMonkey tries to identify two motifs per modules in the upstream sequences of the module member genes. (systemsbiology.net)
  • Overlapping genes are also found to evolve due to the acquisition of an upstream start codon by the downstream gene 7 . (ijpsr.com)
  • Following this, the differentially expressed genes (DEGs) were included in Gene Ontology enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, protein‑protein interaction network and survival analyses. (cancerindex.org)
  • Excision repair cross-complementation group 1 (ERCC1) is a key rate-limiting enzyme in the NER pathway. (hindawi.com)
  • Although genetics have played a dominant role in cancer research, epigenetics (heritable changes in gene function that do not involve alterations in DNA sequence) has become equally important in this field. (aacrjournals.org)
  • Our data have provided evidence for a comparable prediction of clinical outcome in CMF-treated breast cancer patients using conventional clinical variables and gene expression based markers. (lu.se)
  • Therapeutic gene transfer affords a clinically feasible and safe approach to cancer treatment but a more effective modality is needed to improve clinical outcomes. (biomedcentral.com)
  • The potential reversibility of epigenetic modifications renders the enzymes that are responsible for establishment of tumorigenic epigenetic changes important targets for drug development. (aacrjournals.org)
  • In addition to enzymes, B. subtilis is also used for the production of chemicals. (biomedcentral.com)
  • 2009) was utilized as a source of B. subtilis chr3N and chr3C genes. (her2signaling.com)
  • However, a homolog for spoIIR was identified in all six strains, the product of which could interact with SpoIIGA for the processing of pro-σE into active σE, a sigma factor responsible for the expression of ~250 genes in the mother cell of Bacillus subtilis [68]. (peptide-solubility.com)
  • To increase the efficiency of the CD/5-FC pair, InvivoGen has fused the gene encoding uracil phosphoribosyl transferase (UPRT) to the CD gene. (invivogen.com)
  • The gene/parasite could not be changed/generated by the genetic modification. (pberghei.eu)
  • Gene fitness was determined by bioinformatics analysis from available datasets from genetic screenings. (biomedcentral.com)
  • The proposed genes are based on known developmental and genetic processes of sporulation and germination in Bacillus and Clostridium species. (peptide-solubility.com)
  • Here, we review the available literature in relation to drug discovery studies targeting thymidylate biosynthesis in kinetoplastid (genera Trypanosoma and Leishmania) and apicomplexan (Plasmodium spp and Toxoplasma gondii) protozoans. (eurekaselect.com)
  • Combined transfer of therapeutic genes with different modes of actions may be a means to this end. (biomedcentral.com)
  • Therapeutic gene transfer using viral or nonviral vectors has been shown to be clinically feasible and safe. (biomedcentral.com)
  • However, the therapeutic outcome appears not to be high as expected, presumably because the in vivo gene delivery efficiency is low. (biomedcentral.com)
  • Combined transfer of genes with different mechanisms of action may potentate the therapeutic outcome. (biomedcentral.com)
  • This line, which is relatively resistant to FdUrd, produces two structural forms of TS, as determined by mobility of the enzyme in isoelectric focusing polyacrylamide gels. (aspetjournals.org)
  • One form is common to all the cell lines, whereas a variant form, which is more basic and is encoded by a separate structural gene, is unique to HCT 116. (aspetjournals.org)
  • Quantitative reverse transcription-PCR was done to evaluate the gene expression of E2F1, TS , and Survivin . (aacrjournals.org)
  • Potential transcription factor binding sites (TFBS) and CpG islands for regulating ENO gene expression were identified. (edu.au)
  • The top 14 hub genes were subsequently confirmed by reverse transcription‑quantitative polymerase chain reaction in ACC and adrenocortical adenoma samples. (cancerindex.org)
  • Overlapping genes were classified into different categories based on their direction of transcription. (ijpsr.com)
  • The extracted overlapping gene pairs were classified into three directional patterns, namely, 'convergent' (→←), 'unidirectional' (→→, ←←), and 'divergent' (←→) based on their direction of transcription 18 . (ijpsr.com)
  • Human ENO1, ENO2, ENO3, and ENOF1 genes each contained CpG islands in the gene promoter regions consistent with higher-than-average levels of expression. (edu.au)
  • The strain BSK814G2, in which purA was knocked out, and prs , purF and guaB were co-overexpressed, produced 115.2 mg/L of guanosine, which was 4.4-fold higher compared to the control strain constructed by introducing the same gene modifications into the parental strain. (biomedcentral.com)
  • Plasmodium falciparum contains PF3D7_1235600, a previously characterized cSHMT gene (Pfcshmt), and PF3D7_1456100, a putative gene of mSHMT (Pfmshmt). (pberghei.eu)
  • The newly unveiled microRNAs and previously characterized microRNAs have distinct expression patterns. (pharmaceuticalintelligence.com)
  • Immunohistochemistry was done to investigate the protein expression of E2F1, TS, and Survivin. (aacrjournals.org)
  • Overlapping genes have also been identified in various eukaryotic organisms including humans and systematic analysis methods have been developed 1, 2 . (ijpsr.com)
  • The mRNA levels and enzyme activities corresponded to cell cycle progression and cell growth stages. (wikipedia.org)
  • This suggests that although sporulation in Bacillus and D. hafniense DCB-2 have much in common, there are differences in the regulatory mechanism or in the enzyme system for the initiation of sporulation stages. (peptide-solubility.com)
  • The Giardia lamblia vsp gene repertoire: characteristics, genomic organization, and evolution. (mbl.edu)
  • Overlapping genes can be used as rare genomic markers to get insight into the phylogeny of the completely sequenced microbial genomes 13 . (ijpsr.com)
  • The combined gene transfer increased splenic NK cell activity and IFN-γ production by splenocytes. (biomedcentral.com)
  • In order to assess the effects of two different strawberry extracts (whole methanolic extract/anthocyanin-enriched fraction) on the lipid profile and antioxidant status in human hepatocellular carcinoma (HepG2) cells, the triglycerides and LDL-cholesterol content, lipid peroxidation, intracellular reactive oxygen species (ROS) content and antioxidant enzymes' activity on cell lysates were determined. (edu.mx)
  • Measuring these determinants requires tumor tissue and, in the case of gene expression, a technically demanding quantitative PCR procedure. (imrpress.com)
  • PLP plays a vital role in the function of over 100 enzymes that catalyze essential chemical reactions in the human body (4) . (oregonstate.edu)
  • Each black arrow represents a biochemical reaction and the blue and yellow ellipses on the arrows contain the acronyms of the enzymes that catalyze the reactions. (biomedcentral.com)
  • Overlapping genes are more conserved between species than non-overlapping genes mostly because a mutation in the overlapping region causes changes in both genes 11, 12 . (ijpsr.com)
  • It has been documented that high expression of ERCC1 could block the platinum efficacy and cause drug resistance [ 6 ]. (hindawi.com)
  • Topoisomerase I (Topo I) can be an important enzyme with pivotal function in regulating DNA topology[11]. (careersfromscience.org)
  • The present study also emphasizes the significance of overlapping genes in the evolution of these genomes. (ijpsr.com)