ArticleThe Biochemical journal2007
Human nuclear pregnane X receptor cross-talk with CREB to repress cAMP activation of the glucose-6-phosphatase gene.
Article in The Biochemical journal, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 128 citations in OpenAlex.
- Mutation of PXR phosphorylation motif at Ser347 disrupts lipid and bile acid homeostasis in diet-induced metabolic dysfunction-associated steatohepatitis in mice.Drug metabolism and disposition: the biological fate of chemicals · 2026Article
- Pregnane X receptor (NR1I2) deficiency in mice reveals context-dependent regulation of inflammatory homeostasis.Frontiers in immunology · 2026Review
- Physiological Functions and Pathological Roles of PXR.Journal of the Endocrine Society · 2025Review
- CAR: Discovery and development by the pharmacogenetics laboratory at NIEHS, NIH.Pharmacological research · 2025Review
- Insights of direct and indirect regulation of PXR through phosphorylation in fatty liver disease.Molecular pharmacology · 2025Review
- Role of Bile Acid Receptors in the Development and Function of Diabetic Nephropathy.Kidney international reports · 2024Review
- Pregnenolone 16-Alpha Carbonitrile, an Agonist of Rodent Pregnane X Receptor, Regulates Testosterone Biosynthesis in Rodent Leydig Cells.Journal of xenobiotics · 2024Article
- Bile acid metabolism and signaling in health and disease: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- The Pregnane-X receptor regulates steroid synthesis in mouse Leydig cells.Frontiers in endocrinology · 2024Article
- Adipocyte-Derived PXR Signaling Is Dispensable for Diet-Induced Obesity and Metabolic Disorders in Mice.Drug metabolism and disposition: the biological fate of chemicals · 2023Article
- Atypical functions of xenobiotic receptors in lipid and glucose metabolism.Medical review (2021) · 2022Review
- Article
- Mice blocking Ser347 phosphorylation of pregnane x receptor develop hepatic fasting-induced steatosis and hypertriglyceridemia.Biochemical and biophysical research communications · 2022Article
- PXR activation impairs hepatic glucose metabolism partlyActa pharmaceutica Sinica. B · 2022Article
- The role of bile acids in carcinogenesis.Cellular and molecular life sciences : CMLS · 2022Review
- Expression dynamics of pregnane X receptor-controlled genes in 3D primary human hepatocyte spheroids.Archives of toxicology · 2022Article
- Role of bile acids in overweight and obese children and adolescents.Frontiers in endocrinology · 2022Review
- The role of pregnane X receptor (PXR) in substance metabolism.Frontiers in endocrinology · 2022Review
- Regulation of PXR Function by Coactivator and Corepressor Proteins: Ligand Binding Is Just the Beginning.Cells · 2021Review
- Pregnane X receptor exacerbates nonalcoholic fatty liver disease accompanied by obesity- and inflammation-prone gut microbiome signature.Biochemical pharmacology · 2021Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The nuclear PXR (pregnane X receptor) was originally characterized as a key transcription factor that activated hepatic genes encoding drug-metabolizing enzymes. We have now demonstrated that PXR also represses glucagon-activated transcription of the G6Pase (glucose-6-phosphatase) gene by directly binding to CREB [CRE (cAMP-response element)-binding protein]. Adenoviral-mediated expression of human PXR (hPXR) and its activation by rifampicin strongly repressed cAMP-dependent induction of the endogenous G6Pase gene in Huh7 cells. Using the -259 bp G6Pase promoter construct in cell-based transcription assays, repression by hPXR of PKA (cAMP-dependent protein kinase)-mediated promoter activation was delineated to CRE sites. GST (glutathione transferase) pull-down and immunoprecipitation assays were employed to show that PXR binds directly to CREB, while gel-shift assays were used to demonstrate that this binding prevents CREB interaction with the CRE. These results are consistent with the hypothesis that PXR represses the transcription of the G6Pase gene by inhibiting the DNA-binding ability of CREB. In support of this hypothesis, treatment with the mouse PXR activator PCN (pregnenolone 16alpha-carbonitrile) repressed cAMP-dependent induction of the G6Pase gene in primary hepatocytes prepared from wild-type, but not from PXR-knockout, mice, and also in the liver of fasting wild-type, but not PXR-knockout, mice. Moreover, ChIP (chromatin immunoprecipitation) assays were performed to show a decreased CREB binding to the G6Pase promoter in fasting wild-type mice after PCN treatment. Thus drug activation of PXR can repress the transcriptional activity of CREB, down-regulating gluconeogenesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.