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Literature summary for 6.3.4.3 extracted from

  • Zhao, L.; Cheng, Z.; Lu, Z.; Jin, J.
    NAD-dependent methylenetetrahydrofolate dehydrogenase inhibits oral squamous cell carcinoma cell proliferation and promotes apoptosis (2021), Transl. Cancer Res., 10, 1457-1469 .
    View publication on PubMedView publication on EuropePMC

Application

Application Comment Organism
medicine MTHFD1L may be involved in OSCC progression via the c-MYC gene and p53 signaling and may serve as a target and orientation for tumor therapy Homo sapiens

Protein Variants

Protein Variants Comment Organism
additional information short hairpin RNA (shRNA)-induced MTHFD1L silencing, analysis of the effcets on the biological behavior of OSCC cells are assessed in vitro and in vivo, overview. Knockdown of MTHFD1L suppresses cell proliferation, colony formation, and tumorigenesis, while it induces apoptosis in oral squamous cell carcinoma (OSCC). Mechanistically, a microarray analysis shows that MTHFD1L suppresses c-MYC and activates p53 signaling by regulating the protein expression of TP53, GADD45A, FAS and JUN Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
mitochondrion MTHFD1L is a mitochondrial monofunctional enzyme with 10-CHO-THF synthase activity Homo sapiens 5739
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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 + formate + tetrahydrofolate Homo sapiens
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ADP + phosphate + 10-formyltetrahydrofolate
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?
additional information Homo sapiens MTHFD1L directly interacts with the c-MYC proto-oncogene and basic helix-loop-helix (bHLH) transcription factor. MTHFD1L directly interacts with the MAGE family member D1 (MAGED) ?
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Organism

Organism UniProt Comment Textmining
Homo sapiens Q6UB35
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Source Tissue

Source Tissue Comment Organism Textmining
additional information MTHFD1L levels are higher in tumor tissue than in adjacent tissues, RNA analysis and immunohistochemic analysis, overview Homo sapiens
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oral squamous cell carcinoma cell OSCC cell. The p53 pathway might contribute to the abnormal expression of MTHFD1L in OSCC Homo sapiens
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + formate + tetrahydrofolate
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Homo sapiens ADP + phosphate + 10-formyltetrahydrofolate
-
?
additional information MTHFD1L directly interacts with the c-MYC proto-oncogene and basic helix-loop-helix (bHLH) transcription factor. MTHFD1L directly interacts with the MAGE family member D1 (MAGED) Homo sapiens ?
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Synonyms

Synonyms Comment Organism
10-CHO-THF synthase
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Homo sapiens
methylenetetrahydrofolate dehydrogenase 1-like
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Homo sapiens
MTHFD1L
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Homo sapiens
NAD-dependent methylenetetrahydrofolate dehydrogenase
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Homo sapiens

Cofactor

Cofactor Comment Organism Structure
ATP
-
Homo sapiens

Expression

Organism Comment Expression
Homo sapiens the expression of MTHFD1L is significantly affected by the mTORC1-4EBP1-eIF4E axis down

General Information

General Information Comment Organism
malfunction knockdown of MTHFD1L suppresses cell proliferation, colony formation, and tumorigenesis, while it induces apoptosis in oral squamous cell carcinoma (OSCC). Mechanistically, a microarray analysis shows that MTHFD1L suppresses c-MYC and activates p53 signaling by regulating the protein expression of TP53, GADD45A, FAS and JUN. the suppression of MTHFD1L affects c-MYC expression and thereby inhibits tumor cell proliferation and induces apoptosis. MTHFD1L knockdown may affect JUN expression through MAGED and induce cell apoptosis of the tumor. Homo sapiens
physiological function the NAD-dependent methylenetetrahydrofolate dehydrogenase catalyzes the conversion of 10-formyltetrahydrofolate to formate in embryonic and adult mammalian mitochondria. Methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) is a folate cycle enzyme that is involved in the development of various diseases including cancer. Immunohistochemical staining and Kaplan-Meier survival analysis indicate that MTHFD1L upregulation is associated with a poor prognosis in oral squamous cell carcinoma (OSCC). MTHFD1L contributes to the production of NADPH, which is sufficient in combating oxidative stress in OSCC. MTHFD1L directly interacts with the c-MYC proto-oncogene and basic helix-loop-helix (bHLH) transcription factor. MTHFD1L suppresses c-MYC and activates p53 signaling by regulating the protein expression of TP53, GADD45A, FAS and JUN. MTHFD1L directly interacts with the MAGE family member D1 (MAGED). MAGED enhances the phosphorylation of the JUN activator protein 1 (AP-1) transcription factor subunit and activates JUN. Regulation mechanism, overview Homo sapiens