Properties of Tetrahydropteroylpentaglutamate Bound to 10-Formyltetrahydrofolate Dehydrogenase†

Biochemistry ◽  
1996 ◽  
Vol 35 (49) ◽  
pp. 15772-15783 ◽  
Author(s):  
Dong Woon Kim ◽  
Teng Huang ◽  
Douglas Schirch ◽  
Verne Schirch
Keyword(s):  
Formyltetrahydrofolate Dehydrogenase

scholarly journals Knockout of Putative Tumor Suppressor Aldh1l1 in Mice Reprograms Metabolism to Accelerate Growth of Tumors in a Diethylnitrosamine (DEN) Model of Liver Carcinogenesis

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3219
Author(s):  
Natalia I. Krupenko ◽  
Jaspreet Sharma ◽  
Halle M. Fogle ◽  
Peter Pediaditakis ◽  
Kyle C. Strickland ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Chemical Carcinogenesis ◽  
Dependent Manner ◽  
Wild Type ◽  
Liver Carcinogenesis ◽  
Wild Type Littermate ◽  
Tumor Multiplicity ◽  
Accelerate Growth ◽  
Putative Tumor Suppressor ◽  
Formyltetrahydrofolate Dehydrogenase

Cytosolic 10-formyltetrahydrofolate dehydrogenase (ALDH1L1) is commonly downregulated in human cancers through promoter methylation. We proposed that ALDH1L1 loss promotes malignant tumor growth. Here, we investigated the effect of the Aldh1l1 mouse knockout (Aldh1l1−/−) on hepatocellular carcinoma using a chemical carcinogenesis model. Fifteen-day-old male Aldh1l1 knockout mice and their wild-type littermate controls (Aldh1l1+/+) were injected intraperitoneally with 20 μg/g body weight of DEN (diethylnitrosamine). Mice were sacrificed 10, 20, 28, and 36 weeks post-DEN injection, and livers were examined for tumor multiplicity and size. We observed that while tumor multiplicity did not differ between Aldh1l1−/− and Aldh1l1+/+ animals, larger tumors grew in Aldh1l1−/− compared to Aldh1l1+/+ mice at 28 and 36 weeks. Profound differences between Aldh1l1−/− and Aldh1l1+/+ mice in the expression of inflammation-related genes were seen at 10 and 20 weeks. Of note, large tumors from wild-type mice showed a strong decrease of ALDH1L1 protein at 36 weeks. Metabolomic analysis of liver tissues at 20 weeks showed stronger differences in Aldh1l1+/+ versus Aldh1l1−/− metabotypes than at 10 weeks, which underscores metabolic pathways that respond to DEN in an ALDH1L1-dependent manner. Our study indicates that Aldh1l1 knockout promoted liver tumor growth without affecting tumor initiation or multiplicity.

scholarly journals Resolution of rat liver 10-formyltetrahydrofolate dehydrogenase/hydrolase activities.

1988 ◽  
Vol 263 (21) ◽  
pp. 10204-10207
Author(s):  
G L Case ◽  
P J Kaisaki ◽  
R D Steele
Keyword(s):  
Rat Liver ◽  
Formyltetrahydrofolate Dehydrogenase

scholarly journals Cancer cells activate p53 in response to 10-formyltetrahydrofolate dehydrogenase expression

2005 ◽  
Vol 391 (3) ◽  
pp. 503-511 ◽  
Author(s):  
Natalia V. Oleinik ◽  
Natalia I. Krupenko ◽  
David G. Priest ◽  
Sergey A. Krupenko
Keyword(s):  
Cancer Cells ◽  
Ectopic Expression ◽  
A549 Cells ◽  
Dominant Negative ◽  
G1 Arrest ◽  
Transactivation Domain ◽  
Downstream Target ◽  
Formyltetrahydrofolate Dehydrogenase ◽  
Induced Apoptosis ◽  
Hct116 Cells

A folate enzyme, FDH (10-formyltetrahydrofolate dehydrogenase; EC 1.5.1.6), is not a typical tumour suppressor, but it has two basic characteristics of one, i.e. it is down-regulated in tumours and its expression is selectively cytotoxic to cancer cells. We have recently shown that ectopic expression of FDH in A549 lung cancer cells induces G1 arrest and apoptosis that was accompanied by elevation of p53 and its downstream target, p21. It was not known, however, whether FDH-induced apoptosis is p53-dependent or not. In the present study, we report that FDH-induced suppressor effects are strictly p53-dependent in A549 cells. Both knockdown of p53 using an RNAi (RNA interference) approach and disabling of p53 function by dominant-negative inhibition with R175H mutant p53 prevented FDH-induced cytotoxicity in these cells. Ablation of the FDH-suppressor effect is associated with an inability to activate apoptosis in the absence of functional p53. We have also shown that FDH elevation results in p53 phosphorylation at Ser-6 and Ser-20 in the p53 transactivation domain, and Ser-392 in the C-terminal domain, but only Ser-6 is strictly required to mediate FDH effects. Also, translocation of p53 to the nuclei and expression of the pro-apoptotic protein PUMA (Bcl2 binding component 3) was observed after induction of FDH expression. Elevation of FDH in p53 functional HCT116 cells induced strong growth inhibition, while growth of p53-deficient HCT116 cells was unaffected. This implies that activation of p53-dependent pathways is a general downstream mechanism in response to induction of FDH expression in p53 functional cancer cells.

scholarly journals Ethanol-Induced Upregulation of 10-Formyltetrahydrofolate Dehydrogenase Helps Relieve Ethanol-Induced Oxidative Stress

2013 ◽  
Vol 34 (3) ◽  
pp. 498-509 ◽  
Author(s):  
T.-H. Hsiao ◽  
C.-J. Lin ◽  
Y.-S. Chung ◽  
G.-H. Lee ◽  
T.-T. Kao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Formyltetrahydrofolate Dehydrogenase

scholarly journals Identification of Protein-ArginineN-Methyltransferase as 10-Formyltetrahydrofolate Dehydrogenase

1998 ◽  
Vol 273 (42) ◽  
pp. 27374-27382 ◽  
Author(s):  
Sangduk Kim ◽  
Gil Hong Park ◽  
Won A. Joo ◽  
Woon Ki Paik ◽  
Robert J. Cook ◽  
...  
Keyword(s):  
Formyltetrahydrofolate Dehydrogenase

scholarly journals Identification of a heritable deficiency of the folate-dependent enzyme 10-formyltetrahydrofolate dehydrogenase in mice.

1994 ◽  
Vol 91 (24) ◽  
pp. 11338-11342 ◽  
Author(s):  
K. M. Champion ◽  
R. J. Cook ◽  
S. L. Tollaksen ◽  
C. S. Giometti
Keyword(s):  
Formyltetrahydrofolate Dehydrogenase

Baculovirus Expression and Purification of Rat 10-Formyltetrahydrofolate Dehydrogenase

1995 ◽  
Vol 6 (4) ◽  
pp. 457-464 ◽  
Author(s):  
S.A. Krupenko ◽  
D.A. Horstman ◽  
C. Wagner ◽  
R.J. Cook
Keyword(s):  
Expression And Purification ◽  
Baculovirus Expression ◽  
Formyltetrahydrofolate Dehydrogenase

Crystal Structures of the Carboxyl Terminal Domain of Rat 10-Formyltetrahydrofolate Dehydrogenase:  Implications for the Catalytic Mechanism of Aldehyde Dehydrogenases†

Biochemistry ◽  
2007 ◽  
Vol 46 (11) ◽  
pp. 2917-2929 ◽  
Author(s):  
Yaroslav Tsybovsky ◽  
Henry Donato ◽  
Natalia I. Krupenko ◽  
Christopher Davies ◽  
Sergey A. Krupenko
Keyword(s):  
Crystal Structures ◽  
Catalytic Mechanism ◽  
Aldehyde Dehydrogenases ◽  
Terminal Domain ◽  
Carboxyl Terminal Domain ◽  
Carboxyl Terminal ◽  
Formyltetrahydrofolate Dehydrogenase

scholarly journals On the Role of Conserved Histidine 106 in 10-Formyltetrahydrofolate Dehydrogenase Catalysis

2001 ◽  
Vol 276 (26) ◽  
pp. 24030-24037 ◽  
Author(s):  
Sergey A. Krupenko ◽  
Alexander P. Vlasov ◽  
Conrad Wagner
Keyword(s):  
Formyltetrahydrofolate Dehydrogenase
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