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Literature summary for 6.3.2.17 extracted from
- Effects of folylpolyglutamate synthase modulation on global and gene-specific DNA methylation and gene expression in human colon and breast cancer cells (2016), J. Nutr. Biochem., 29, 27-35 .
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| gene FPGS, gene-specific promoter CpG DNA methylation analysis and global DNA methylation analysis, recombinant FPGS overexpression in HCT-116 and MDA-MB-435 cells, quantitative RT-PCR enzyme expression analysis | Homo sapiens |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| additional information | FPGS overexpression and suppression in colon and breast cancers cells, HCT-116 and MDA-MB-435 cell lines, FPGS inhibition is developed by transfecting HCT-116 cells and MDA-MB-435 cells with the antisense FPGS cDNA and the FPGS-targeted small interfering RNA (siRNA), respectively. FPGS overexpression is associated with significantly lower (by 18%) global DNA methylation than controls in HCT-116 cells, but is associated with significantly higher (by 13%) global DNA methylation than controls in MDA-MB-435 cells. FPGS suppression is associated with significantly higher (by 12%) global DNA methylation than controls in HCT-116 cells, but has no effect in MDA-MB-435 cells. In MDA-MB-435 cells, 2239 differentially methylated genes (1161 hypermethylated and 1078 hypomethylated) occur in response to FPGS overexpression and 2024 differentially methylated genes (1150 hypermethylated and 874 hypomethylated) occur in response to FPGS suppression. Differentially methylated genes are involved in molecular transport and cell death in both the FPGS-overexpressed and silenced MDA-MB-435 cells | Homo sapiens |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Mg2+ | required | Homo sapiens |  |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + tetrahydropteroyl-[gamma-Glu]n + L-glutamate | Homo sapiens | - |
ADP + phosphate + tetrahydropteroyl-[gamma-Glu]n+1 | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| breast cancer cell | - |
Homo sapiens | - |
| colon cancer cell | - |
Homo sapiens | - |
| HCT-116 cell | - |
Homo sapiens | - |
| MDA-MB-435 cell | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + tetrahydropteroyl-[gamma-Glu]n + L-glutamate | - |
Homo sapiens | ADP + phosphate + tetrahydropteroyl-[gamma-Glu]n+1 | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| Folylpolyglutamate synthase | - |
Homo sapiens |
| FPGS | - |
Homo sapiens |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| ATP | - |
Homo sapiens | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| malfunction | FPGS modulation (overexpression or silencing) affects global and promoter CpG DNA methylation and expression of several genes involved in important biological pathways, molecular and cellular functions of genes associated with altered expression and promoter DNA methylation in the FPGS-modulated HCT116 and MDA-MB-435 cells, overview. FPGS-specific altered expression changes are regulated by promoter DNA methylation in MDA-MB-435 cells. In the MDA-MB-435 cells overexpressing FPGS, 41 hypermethylated and downregulated genes are primarily associated with drug metabolism, molecular transport, cell cycle, cell death and cellular assembly and organization, while 54 hypomethylated and upregulated genes are mainly involved in cellular movement, cell-to-cell signaling and interaction, cell death, posttranslational modification and cell signaling. In the FPGS-silenced MDA-MB-435 cells, 30 downregulated and 13 upregulated genes with an inverse association with promoter DNA methylation changes are related to cellular movement and cell cycle. In HCT-116 cells, 24 genes are upregulated in response to FPGS overexpression and downregulated in response to FPGS suppression, and these genes are associated with gene expression, cell-to-cell signaling and interaction, cell morphology, cellular assembly and organization and cell death. Twenty-one genes that are downregulated in response to FPGS overexpression and upregulated in response to FPGS suppression in HCT-116 cells, are involved in cell cycle, cellular compromise, lipid metabolism, small-molecule biochemistry, and vitamin and mineral metabolism | Homo sapiens |
| physiological function | folylpolyglutamate synthase (FPGS) plays a critical role in intracellular folate homeostasis. FPGS-induced polyglutamylated folates are better substrates for several enzymes involved in the generation of S-adenosylmethionine, the primary methyl group donor, and hence FPGS modulation may affect DNA methylation. DNA methylation is an important epigenetic determinant in gene expression and aberrant DNA methylation is mechanistically linked cancer development. FPGS-mediated polyglutamylation-induced changes in total intracellular folate concentrations and in contents of polyglutamylated folates play an important role in DNA methylation as polyglutamylated folates are better substrates for methylenetetrahydrofolate reductase and methionine synthase, both of which are involved in the generation of S-adenosyl-L-methione. Role of FPGS modulation in DNA methylation and its associated downstream functional effects, overview | Homo sapiens |
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