ArticleMolecular endocrinology (Baltimore, Md.)2015
CAR Suppresses Hepatic Gluconeogenesis by Facilitating the Ubiquitination and Degradation of PGC1α.
Article in Molecular endocrinology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed.
- Molecular regulation of PGC-1α: from protein-protein interactions and post-translational modifications to pharmacological modulation.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Hepatic Glucocorticoid Receptor Action and Glucose Homeostasis.Endocrine reviews · 2026Review
- CAR: Discovery and development by the pharmacogenetics laboratory at NIEHS, NIH.Pharmacological research · 2025Review
- Constitutive androstane receptor, liver pathophysiology and chemical contaminants: current evidence and perspectives.Frontiers in endocrinology · 2025Review
- Liver matrin-3 protects mice against hepatic steatosis and stress response via constitutive androstane receptor.Molecular metabolism · 2024Article
- Steatotic liver disease induced by TCPOBOP-activated hepatic constitutive androstane receptor: primary and secondary gene responses with links to disease progression.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- The Role of Nuclear Receptors in the Pathogenesis and Treatment of Non-alcoholic Fatty Liver Disease.International journal of biological sciences · 2024Review
- PPARα Induces the Expression of CAR That Works as a Negative Regulator of PPARα Functions in Mouse Livers.International journal of molecular sciences · 2023Article
- Article
- Atypical functions of xenobiotic receptors in lipid and glucose metabolism.Medical review (2021) · 2022Review
- Clinical Relevance of the Constitutive Androstane Receptor.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- The xenobiotic receptors PXR and CAR in liver physiology, an update.Biochimica et biophysica acta. Molecular basis of disease · 2021Review
- Article
- Nuclear receptor phosphorylation in xenobiotic signal transduction.The Journal of biological chemistry · 2020Review
- Constitutive Androstane Receptor: A Peripheral and a Neurovascular Stress or Environmental Sensor.Cells · 2020Review
- Review
- Noncanonical Constitutive Androstane Receptor Signaling in Gene Regulation.International journal of molecular sciences · 2020Review
- Inhibition of Estrogen Sulfotransferase (Journal of the American Society of Nephrology : JASN · 2020Article
- Hepatocyte-specific Nrf2 deficiency mitigates high-fat diet-induced hepatic steatosis: Involvement of reduced PPARγ expression.Redox biology · 2020Article
- Current trends in drug metabolism and pharmacokinetics.Acta pharmaceutica Sinica. B · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
Abstract
The constitutive androstane receptor (CAR) and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC1α) are master regulators of drug metabolism and gluconeogenesis, respectively. In supporting the cross talk between drug metabolism and energy metabolism, activation of CAR has been shown to suppress hepatic gluconeogenesis and ameliorate hyperglycemia in vivo, but the underlying molecular mechanism remains elusive. In this study, we demonstrated that CAR suppressed hepatic gluconeogenic gene expression through posttranslational regulation of the subcellular localization and degradation of PGC1α. Activated CAR translocated into the nucleus and served as an adaptor protein to recruit PGC1α to the Cullin1 E3 ligase complex for ubiquitination. The interaction between CAR and PGC1α also led to their sequestration within the promyelocytic leukemia protein-nuclear bodies, where PGC1α and CAR subsequently underwent proteasomal degradation. Taken together, our findings revealed an unexpected function of CAR in recruiting an E3 ligase and targeting the gluconeogenic activity of PGC1α. Both drug metabolism and gluconeogenesis are energy-demanding processes. The negative regulation of PGC1α by CAR may represent a cellular adaptive mechanism to accommodate energy-restricted conditions.
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Registered trials
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.