ArticlePloS one2014
Multiple E-boxes in the distal promoter of the rat pyruvate carboxylase gene function as a glucose-responsive element.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- Insulin therapy in acute decompensation of holocarboxylase synthetase deficiency with hyperglycemia and ketoacidosis.Molecular genetics and metabolism reports · 2024Article
- USF2 promotes autophagy and proliferation in chronic lymphocytic leukemia by inhibiting STUB1-induced NFAT5 ubiquitination.Annals of hematology · 2024Article
- Review
- USF2 reduces BMP3 expression via transcriptional activation of miR-34a, thus promoting osteogenic differentiation of BMSCs.Journal of bone and mineral metabolism · 2021Article
- Article
- Roles of pyruvate carboxylase in human diseases: from diabetes to cancers and infection.Journal of molecular medicine (Berlin, Germany) · 2018Review
- Dietary Macronutrient Composition Directs ChREBP Isoform Expression and Glucose Metabolism in Mice.PloS one · 2016Article
- ChREBP Regulates Itself and Metabolic Genes Implicated in Lipid Accumulation in β-Cell Line.PloS one · 2016Article
- Mitochondria in Cancer Energy Metabolism: Culprits or Bystanders?Toxicological research · 2015Review
- The minimal promoter region of the dense-core vesicle protein IA-2: transcriptional regulation by CREB.Acta diabetologica · 2015Article
- Protein kinases as switches for the function of upstream stimulatory factors: implications for tissue injury and cancer.Frontiers in pharmacology · 2015Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Pyruvate carboxylase (PC) is an anaplerotic enzyme that regulates glucose-induced insulin secretion in pancreatic islets. Dysregulation of its expression is associated with type 2 diabetes. Herein we describe the molecular mechanism underlying the glucose-mediated transcriptional regulation of the PC gene. Incubation of the rat insulin cell line INS-1 832/13 with glucose resulted in a 2-fold increase in PC mRNA expression. Transient transfections of the rat PC promoter-luciferase reporter construct in the above cell line combined with mutational analysis indicated that the rat PC gene promoter contains the glucose-responsive element (GRE), comprising three canonical E-boxes (E1, E3 and E4) and one E-box-like element (E2) clustering between nucleotides -546 and -399, upstream of the transcription start site. Mutation of any of these E-boxes resulted in a marked reduction of glucose-mediated transcriptional induction of the reporter gene. Electrophoretic mobility shift assays revealed that the upstream stimulatory factors 1 and 2 (USF1 and USF2) bind to E1, the Specificity Protein-1 (Sp1) binds to E2, USF2 and the carbohydrate responsive element binding protein (ChREBP) binds to E4, while unknown factors binds to E3. High glucose promotes the recruitment of Sp1 to E2 and, USF2 and ChREBP to E4. Silencing the expression of Sp1, USF2 and ChREBP by their respective siRNAs in INS-1 832/13 cells blunted glucose-induced expression of endogenous PC. We conclude that the glucose-mediated transcriptional activation of the rat PC gene is regulated by at least these three transcription factors.
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