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Folylpolyglutamate synthase

folylpolyglutamate synthetase, FPGS, folylpoly-gamma-glutamate synthetase, folylpolyglutamate synthase
This gene encodes the folylpolyglutamate synthetase enzyme. This enzyme has a central role in establishing and maintaining both cytosolic and mitochondrial folylpolyglutamate concentrations and, therefore, is essential for folate homeostasis and the survival of proliferating cells. This enzyme catalyzes the ATP-dependent addition of glutamate moieties to folate and folate derivatives. While several transcript variants may exist for this gene, the full-length natures of only two have been biologically validated to date. These two variants encode distinct isoforms. [provided by RefSeq, Jul 2008] (from NCBI)
Top mentioned proteins: ACID, HAD, CAN, dihydrofolate reductase, V1a
Papers on folylpolyglutamate synthetase
Association between mRNA expression of chemotherapy-related genes and clinicopathological features in colorectal cancer: A large-scale population analysis.
New
Fukushima et al., Tokyo, Japan. In Int J Mol Med, Jan 2016
In this study, primary tumors obtained from 1,129 patients with colorectal cancer were used to measure the mRNA expression levels of the following genes associated with the effects of standard chemotherapy for colorectal cancer: 5-fluorouracil (5-FU)-related thymidylate synthase (TYMS), dihydropyrimidine dehydrogenase (DPYD) and thymidine phosphorylase (TYMP); folate-related dihydrofolate reductase (DHFR), folylpolyglutamate synthase (FPGS) and gamma-glutamyl hydrolase (GGH); irinotecan-related topoisomerase I (TOP1); oxaliplatin-related excision repair cross-complementing 1 (ERCC1); biologic agent-related vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR).
Folylpolyglutamate synthetase splicing alterations in acute lymphoblastic leukemia are provoked by methotrexate and other chemotherapeutics and mediate chemoresistance.
New
Cloos et al., Amsterdam, Netherlands. In Int J Cancer, Dec 2015
We have recently shown that impaired folylpolyglutamate synthetase (FPGS) splicing possibly contributes to the loss of FPGS activity in MTX-resistant leukemia cell line models and adult leukemia patients.
Validating Internal Control Genes for the Accurate Normalization of qPCR Expression Analysis of the Novel Model Plant Setaria viridis.
Alves-Ferreira et al., Rio de Janeiro, Brazil. In Plos One, 2014
The best-ranked pair of reference genes from the developmental dataset included genes that encoded a phosphoglucomutase and a folylpolyglutamate synthase; genes that encoded a cullin and the same phosphoglucomutase as above were the most stable genes in the leaf gradient dataset.
Mutation Screening and Association Study of the Folylpolyglutamate Synthetase (FPGS) Gene with Susceptibility to Childhood Acute Lymphoblastic Leukemia.
Rerkamnuaychoke et al., Thailand. In Asian Pac J Cancer Prev, 2014
BACKGROUND: Folylpolyglutamate synthetase (FPGS), an important enzyme in the folate metabolic pathway, plays a central role in intracellular accumulation of folate and antifolate in several mammalian cell types.
Loss of function of folylpolyglutamate synthetase 1 reduces lignin content and improves cell wall digestibility in Arabidopsis.
Tang et al., Ardmore, United States. In Biotechnol Biofuels, 2014
Given the link between the C1 and phenylpropanoid pathways, we evaluated whether folylpolyglutamate synthetase (FPGS), an enzyme that catalyzes the addition of a glutamate tail to folates to form folylpolyglutamates, can be a viable target for reducing cell wall recalcitrance in plants.
[A novel missense mutation of folypolyglutamate synthetase gene].
GeneRIF
Yang et al., Shenzhen, China. In Zhongguo Dang Dai Er Ke Za Zhi, 2012
A novel missense mutation 502/490 T>C (L151/101P) in exon 5 of FPGS gene is firstly found in Chinese Han children, and the cytosolic and mitochondrial variants display allelic frequencies of 0.70 % and 0.47 % respectively.
Intracellular disposition of methotrexate in acute lymphoblastic leukemia in children.
Review
Jacqz-Aigrain et al., Paris, France. In Curr Drug Metab, 2012
MTXG₁ is metabolized to active methotrexate polyglutamates (MTXPG) with sequential gamma-linkage of 2 to 6 glutamyl residues by the folylpolyglutamate synthetase (FPGS).
[The mbr-FPGS efficient expression plasmid enhances the sensitivity of Jurkat cells to methotrexate].
GeneRIF
Sun et al., Nanjing, China. In Yi Chuan, 2012
The mbr enhanced the expression of FPGS significantly and increased sensitivity of Jurkat cells to MTX efficiently.
Genetic variation in folylpolyglutamate synthase and gamma-glutamyl hydrolase and plasma homocysteine levels in the Singapore Chinese Health Study.
GeneRIF
Robien et al., Minneapolis, United States. In Mol Genet Metab, 2012
This is one of the first studies to assess FPGS and GGH genetic variants in relation to plasma homocysteine.
In vivo evidence for a significant role of folylpolyglutamate synthase in combined chemotherapy with oral fluoropyrimidine, UFT or S-1, and leucovorin.
GeneRIF
Fukushima et al., Tokushima, Japan. In Oncol Rep, 2011
intratumor FPGS plays an important role in the efficacy of oral fluoropyrimidine plus LV therapy for colorectal cancer.
[Differential gene expression of folylpolyglutamate synthetase in cytoplasm and mitochondria in acquired methotrexate enantiomers resistant to lung cancer A549 cell lines].
GeneRIF
Shen et al., Hefei, China. In Zhonghua Yi Xue Za Zhi, 2011
The expression of mFPGS was different in A549 cells exposed to different methotrexate enantiomers.
Phase II trial of pemetrexed plus bevacizumab for second-line therapy of patients with advanced non-small-cell lung cancer: NCCTG and SWOG study N0426.
Impact
Zinner et al., Buffalo, United States. In J Clin Oncol, 2010
Polymorphisms in genes responsible for pemetrexed transport (reduced folate carrier [SLC19A1]) and metabolism (folylpolyglutamate synthase [FPGS] and gamma-glutamyl hydrolase [GGH]) evaluated in germline DNA (blood) were correlated with treatment outcome.
Recent advances in classical and non-classical antifolates as antitumor and antiopportunistic infection agents: Part II.
Review
Kurup et al., Pittsburgh, United States. In Anticancer Agents Med Chem, 2008
A major mechanism of tumor resistance to clinically useful antifolates is based on their need for polyglutamylation via the enzyme folylpoly-gamma-glutamate synthetase (FPGS).
Recent advances in classical and non-classical antifolates as antitumor and antiopportunistic infection agents: part I.
Review
Kurup et al., Pittsburgh, United States. In Anticancer Agents Med Chem, 2007
A major mechanism of tumor resistance to clinically useful antifolates is based on their need for polyglutamylation via the enzyme folylpoly-gamma-glutamate synthetase (FPGS).
Folate Biosynthesis, Reduction, and Polyglutamylation and the Interconversion of Folate Derivatives.
Matthews et al., In Ecosal Plus, 2007
Second, the pteridine portion of folate is made from GTP and coupled to PABA to generate dihydropteroate, and the bifunctional protein specified by folC, dihydrofolate synthetase, or folylpolyglutamate synthetase, adds the initial glutamate molecule to form dihydrofolate (H2PteGlu1, or dihydropteroylmonoglutamate).
Molecular basis of antifolate resistance.
Review
Assaraf, Haifa, Israel. In Cancer Metastasis Rev, 2007
(Anti)folates are retained intracellularly via polyglutamylation catalyzed by folylpoly-gamma-glutamate synthetase (FPGS).
[Pemetrexed: from preclinic to clinic].
Review
Lokiec et al., Lille, France. In Bull Cancer, 2006
On the other hand, the polyglutamation of the product by the folylpolyglutamate synthetase increases considerably its activity notably towards the thymidylate synthase.
Phase I study of an oral formulation of ZD9331 administered daily for 28 days.
Impact
Fleming et al., Chicago, United States. In J Clin Oncol, 2003
PURPOSE: To define the maximum-tolerated dose and dose-limiting toxicities (DLTs) of an oral formulation of ZD9331, a novel thymidylate synthase inhibitor that is not a substrate for folylpolyglutamate synthase.
Prognostic value of tumoral thymidylate synthase and p53 in metastatic colorectal cancer patients receiving fluorouracil-based chemotherapy: phenotypic and genotypic analyses.
Impact
Milano et al., Nice, France. In J Clin Oncol, 2002
Thymidylate synthase (TS), folylpolyglutamate synthetase, and dihydropyrimidine dehydrogenase were measured by radioenzymatic assays; TS promoter polymorphism (2R/2R v 2R/3R v 3R/3R) was determined by polymerase chain reaction; and p53 protein and mutations were analyzed by immunoluminometric assay and denaturing gradient gel electrophoresis, respectively.
Linkage of markers controlling consecutive biochemical steps in CHO cells as demonstrated by chromosome transfer.
Impact
Siminovitch et al., In Cell, 1977
Gat- is a glycine-, adenosine- and thymidine-requiring auxotrophic mutant with a lesion in folylpolyglutamate synthetase, an enzyme responsible for addition of glutamates to folate residues.
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