Methylenetetrahydrofolate Dehydrogenase (NADP+ Dependent) 2, Methenyltetrahydrofolate Cyclohydrolase Protéines (MTHFD2)

Mouse (Murine) Methylenetetrahydrofolate Dehydrogenase (NADP+ Dependent) 2, Methenyltetrahydrofolate Cyclohydrolase (MTHFD2) interaction partners

1. Data suggest that Ad4BP plays role in regulation of intracellular NADPH concentration via transcription of Me1 and Mthfd2 genes in adrenocortical cells. (Ad4BP = nuclear receptor subfamily 5 group A member 1; Me1 = malic enzyme 1; Mthfd2 = bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase)

2. Mammalian mitochondrial methylenetetrahydrofolate dehydrogenase-cyclohydrolase derived from a trifunctional methylenetetrahydrofolate dehydrogenase-cyclohydrolase-synthetase.

3. results demonstrate a metabolic role for NAD+ dependent methylenetetrahydrofolate dehydrogenase-cyclohydrolase in supporting purine biosynthesis

4. Results describe the ubiquitous expression of NAD-dependent methylenetetrahydrofolate dehydrogenase-cyclohydrolase in mouse embryos, suggesting it has a broad role during embryogenesis.

5. A mutation in methylenetetrahydrofolate reductase (MTHFR) gene, may contribute to the risk of both arterial and deep-vein thrombosis in patients with nephrotic syndrome.

Human Methylenetetrahydrofolate Dehydrogenase (NADP+ Dependent) 2, Methenyltetrahydrofolate Cyclohydrolase (MTHFD2) interaction partners

1. Cancer cells retain expression of both MTHFD isozymes, but only MTHFD2 displays prominent upregulation in cancer.

2. Therapies targeting MTHFD2 may eradicate tumors and prevent recurrence.

3. endothelial cells undergo MTHFD2-mediated reprogramming toward serine-glycine and mitochondrial one-carbon metabolism to compensate for the loss of ATP in response to oxidized phospholipids during atherosclerosis

4. Knocking down MTHFD2 expression in renal cell carcinoma cells, decreased cell proliferation, migration, and invasion were observed and accompanied by the reduced expression of vimentin.

5. miR-92a inhibits proliferation and induces apoptosis by directly regulating MTHFD2 expression in AML.

6. metabolic alterations in MCF7 cells observed as a consequence of MTHFD2 suppression

7. crystal structure of MTHFD2 in complex with a substrate-based inhibitor and the enzyme cofactors NAD(+) and inorganic phosphate.

8. Mechanistically, MYC regulates the expression of MTHFD2, and MTHFD2 knockdown suppresses the TCA cycle.

9. siRNA-mediated silencing of MTHFD2 inhibited migration, invasion and epithelial-mesenchymal transition progression in hepatocellular carcinoma (HCC) cell lines, but no obvious effects on cell proliferation, apoptosis or cell cycle distribution were detected. MTHFD2 is overexpressed in HCC, and is associated with poor prognosis and cellular features connected to metastatic disease.

10. These findings suggest a previously unknown role for MTHFD2 in cancer cell proliferation, adding to its known function in mitochondrial folate metabolism.

11. The highest scoring pathway is mitochondrial one-carbon metabolism and is centred on MTHFD2.

12. Data indicate that methylenetetrahydrofolate dehydrogenase (NADP + -dependent) 2 (MTHFD2)was differentially expressed in breast cancer tissue, suggesting as a prognostic factor and a potential therapeutic target for future breast cancer treatments.

13. Data indicate that the reduced vimentin expression in response to EPHB4, WIPF2 and MTHFD2 silencing was observed at mRNA and protein levels.