FPGS

Last update 08 May 2025

Basic Info

Synonyms

Folylpoly-gamma-glutamate synthetase, folylpolyglutamate synthase, Folylpolyglutamate synthase, mitochondrial

+ [3]

Introduction

Catalyzes conversion of folates to polyglutamate derivatives allowing concentration of folate compounds in the cell and the intracellular retention of these cofactors, which are important substrates for most of the folate-dependent enzymes that are involved in one-carbon transfer reactions involved in purine, pyrimidine and amino acid synthesis. Unsubstituted reduced folates are the preferred substrates. Metabolizes methotrexate (MTX) to polyglutamates.

100 Clinical Results associated with FPGS

100 Translational Medicine associated with FPGS

0 Patents (Medical) associated with FPGS

568

Literatures (Medical) associated with FPGS

01 Apr 2025·Plant Molecular Biology

Chemically-induced cellular stress signals are transmitted to alternative splicing via UsnRNA levels to alter gene expression in Arabidopsis thaliana

Article

Author: Sano, Ryosuke ; Arae, Toshihiro ; Demura, Taku ; Ishibashi, Kodai ; Takahashi, Hirokazu ; Ohtani, Misato

AbstractAlternative pre-mRNA splicing (AS) is a crucial regulatory layer of gene expression in eukaryotes. AS patterns can change in response to abiotic and biotic stress, allowing cellular functions to adapt to environmental conditions. Here, we examined the effects of cellular stress-inducing chemicals on AS-mediated gene regulation in Arabidopsis thaliana by investigating the alternatively spliced forms of SERINE-ARGININE PROTEIN30 (SRp30) and U1-70 K, encoding splicing factors, as well as ASCORBATE PEROXIDASE3 (APX3) and FOLYLPOLYGLUTAMATE SYNTHASE3 (FPGS3), encoding enzymes important for stress responses. Disrupting key cellular activities, including nitric oxide metabolism, ATPase activity, plastid function, and genome stability, affected AS patterns in Arabidopsis. Stress treatment altered the abundance of uridine-rich small nuclear RNAs (UsnRNAs), especially U1 snRNAs, which are essential non-coding RNA components of U1 small nuclear ribonucleoproteins (U1 snRNPs), suggesting that abnormalities in AS are partially mediated by changes in U1 snRNA levels. The shoot redifferentiation defectice2-1 (srd2-1) mutant defective for snRNA transcription was hypersensitive for stress treatment, since it showed changes in AS patterns at lower concentrations of stress inducers to compare with the wild type. Together, our data suggest that cellular stress can influence gene expression in plants by regulating AS, which is partially regulated by UsnRNA levels through the SRD2-mediated snRNA transcription.

01 Nov 2024·Translational Cancer Research

Construction of ferroptosis and pyroptosis model to assess the prognosis of gastric cancer patients based on bioinformatics

Article

Author: Yao, Hongfeng ; Yang, Chen ; Jin, Weidong ; Wang, Dong ; Li, Keyi ; Tang, Lusheng ; Wu, Gaoping ; Zhou, Yi ; Shi, Hanlu

BackgroundGastric cancer (GC) is a malignancy with a grim prognosis, ranking as the second most common cause of cancer-related deaths globally. Various investigations have demonstrated the substantial involvement of ferroptosis and pyroptosis in the advancement of tumors. Nevertheless, the precise molecular mechanisms by which distinct genes associated with ferroptosis and pyroptosis influence the tumor microenvironment (TME) in GC remain elusive. Therefore, this study aims to elucidate the role of ferroptosis and pyroptosis in GC and provide insigths for GC therapy and prognosis evaluation.MethodsThe data including gene expression, clinicopathological characteristics and survival information of GC samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts were collected, and the expression level of ferroptosis and pyroptosis genes (FPGs) in GC samples were analyzed. Consensus clustering analysis, Cox logistic regression, principal component analysis (PCA), and the "survival", "survminer", "limma", "ggplot2" and other packages in R were utilized to compare the differences among different groups. In the level of GC cells, cell viability experiments were conducted by Cell Counting Kit-8 (CCK-8) assay.ResultsThrough the analysis of the expression level of FPGs in GC samples from the TCGA and GEO cohorts, twenty-three prognostic-related and differentially expressed FPGs were collected for further analysis. Through consensus clustering analysis, three distinct patterns of FPGs were identified and found to be correlated with clinicopathological characteristics, immune cell infiltration, and prognosis in patients with GC. Subsequently, 684 prognostic-related genes from 1,082 pattern-related differentially expressed genes (DEGs) were screened for constructing the FPG_Score system to quantify FPGs patterns in individual GC patients and predict the prognosis. The analysis indicated that GC patients with high FPG_Score exhibited improved survival rates, increased tumor mutation burden (TMB), higher microsatellite instability (MSI), and elevated programmed cell death protein ligand 1 (PD-L1) expression. These patients with high FPG_Score were more likely to benefit from immunotherapy and had a more favorable prognosis.ConclusionsOur study innovatively provided a comprehensive analysis of FPGs in GC, and constructed the FPG_Score system for stratification of individual patients, so as to predict its benefit from immunotherapy and prognosis.

01 Nov 2024·Birth Defects Research

Higher Incidence of Common Polymorphisms in the Genes of Folate and Methionine Cycles in Children With Orofacial Clefs and Congenital Heart Defects Compared to their Unaffected Siblings

Article

Author: Geršak, Borut ; Eberlinc, Andreja ; Šmid, Alenka ; Kek, Tina ; Geršak, Ksenija ; Vidmar Golja, Maša ; Mazič, Uroš ; Mlinarič‐Raščan, Irena ; Karas Kuželički, Nataša

ABSTRACTBackgroundUninterrupted folate metabolism plays a vital role in embryonic development, ensuring a supply of one‐carbon‐activated folate cofactors for essential processes. Folate deficiency has been implicated in the development of orofacial clefts (OFC) and congenital heart disease (CHD). Although both malformations have been extensively studied in lieu of folate deficiency, the results of corresponding studies are ambiguous due to the interplay of maternal and fetal genomes controlling folate metabolism in the developing fetus.MethodsWe used the innovative study design to compare affected and unaffected siblings from the same mother, thus minimizing the effect of the maternal genome. Thus, it might be possible to identify genetic markers of congenital malformations that pertain exclusively to the child. This study compared demographic and environmental factors between OFC or CHD‐affected and unaffected pregnancies as well as the presence of polymorphisms in genes of folate metabolism between OFC or CHD‐affected and unaffected siblings.ResultsOnly the maternal fever in the first trimester was a risk factor for OFC, whereas the maternal advanced age, medication administration, and common polymorphism in the FPGS gene increased the risk of CHD formation. Both OFC and CHD formation were associated with a higher number of variant loci in genes of folate–methionine cycles.ConclusionsBoth OFC and CHD formation were associated with a higher number of mutated loci in genes of folate–methionine cycles, indicating polygenic and possibly multifactorial inheritance.

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