Carmen Lafita-Navarro, M.; Perez-Castro, Lizbeth; Zacharias, Lauren G.; Barnes, Spencer; DeBerardinis, Ralph J.; Conacci-Sorrell, Maralice published the artcile< The transcription factors aryl hydrocarbon receptor and MYC cooperate in the regulation of cellular metabolism>, Quality Control of 58-97-9, the main research area is fibroblast cellular metabolism transcription factors aryl hydrocarbon receptor MYC; MYC (c-Myc); aryl hydrocarbon receptor (AHR); cancer; gene regulation; glioblastoma; glycolysis; metabolism; metabolomics; oncogene; pyrimidine.
The transcription factor AHR (aryl hydrocarbon receptor) drives the expression of genes involved in detoxification pathways in cells exposed to pollutants and other small mols. Moreover, AHR supports transcriptional programs that promote ribosome biogenesis and protein synthesis in cells stimulated to proliferate by the oncoprotein MYC. Thus, AHR is necessary for the proliferation of MYC-overexpressing cells. To define metabolic pathways in which AHR cooperates with MYC in supporting cell growth, here we used LC-MS-based metabolomics to examine the metabolome of MYC-expressing cells upon AHR knockdown. We found that AHR knockdown reduced lactate, S-lactoylglutathione, N-acetyl-L-alanine, 2-hydroxyglutarate, and UMP levels. Using our previously obtained RNA sequencing data, we found that AHR mediates the expression of the UMP-generating enzymes dihydroorotate dehydrogenase (quinone) (DHODH) and uridine monophosphate synthetase (UMPS), as well as lactate dehydrogenase A (LDHA), establishing a mechanism by which AHR regulates lactate and UMP production in MYC-overexpressing cells. AHR knockdown in glioblastoma cells also reduced the expression of LDHA (and lactate), DHODH, and UMPS but did not affect UMP levels, likely because of compensatory mechanisms in these cells. Our results indicate that AHR contributes to the regulation of metabolic pathways necessary for the proliferation of transformed cells.
Journal of Biological Chemistry published new progress about Animal gene Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (ALDOA). 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, Quality Control of 58-97-9.
Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem