ArticleDrug metabolism and disposition: the biological fate of chemicals2013
RBCK1, an E3 ubiquitin ligase, interacts with and ubiquinates the human pregnane X receptor.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Expression of the three components of linear ubiquitin assembly complex in breast cancer.PloS one · 2018Trial
- Vatalanib population pharmacokinetics in patients with myelodysplastic syndrome: CALGB 10105 (Alliance).British journal of clinical pharmacology · 2014Trial
- C-terminal Fragment Generated by HOIL-1 Cleavage Suppresses Inflammatory Responses of Myeloid Cells to Alleviate Colitis.Theranostics · 2026Article
- S-nitrosylation attenuates pregnane X receptor hyperactivity and acetaminophen-induced liver injury.JCI insight · 2024Article
- The F-box-only protein 44 regulates pregnane X receptor protein level by ubiquitination and degradation.Acta pharmaceutica Sinica. B · 2023Article
- Exploring the Role of Ubiquitin-Proteasome System in Parkinson's Disease.Molecular neurobiology · 2022Review
- Article
- Non-lysine ubiquitylation: Doing things differently.Frontiers in molecular biosciences · 2022Review
- Insights into the critical role of the PXR in preventing carcinogenesis and chemotherapeutic drug resistance.International journal of biological sciences · 2022Review
- Review
- Review
- PXR: More Than Just a Master Xenobiotic Receptor.Molecular pharmacology · 2018Review
- Acetylation of lysine 109 modulates pregnane X receptor DNA binding and transcriptional activity.Biochimica et biophysica acta · 2016Article
- A SUMO-acetyl switch in PXR biology.Biochimica et biophysica acta · 2016Article
- Xenobiotic Receptor-Mediated Regulation of Intestinal Barrier Function and Innate Immunity.Nuclear receptor research · 2016Article
- SUMOylation and Ubiquitylation Circuitry Controls Pregnane X Receptor Biology in Hepatocytes.Drug metabolism and disposition: the biological fate of chemicals · 2015Article
- Pregnane X receptor and drug-induced liver injury.Expert opinion on drug metabolism & toxicology · 2014Review
- Stability of the human pregnane X receptor is regulated by E3 ligase UBR5 and serine/threonine kinase DYRK2.The Biochemical journal · 2014Article
- Post-translational and post-transcriptional modifications of pregnane X receptor (PXR) in regulation of the cytochrome P450 superfamily.Current drug metabolism · 2013Review
- Regulation of PXR in drug metabolism: chemical and structural perspectives.Expert opinion on drug metabolism & toxicologyReview
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The pregnane X receptor (PXR, NR1I2) plays a pivotal role in the disposition and detoxification of numerous foreign and endogenous chemicals by increasing transcription of numerous target genes, including phase I and II drug-metabolizing enzymes and transporters. In the present study, yeast two-hybrid screening identified an E3 ubiquitin ligase, RBCK1 (Ring-B-box-coiled-coil protein interacting with protein kinase C-1), as a human pregnane X receptor (hPXR)-interacting protein. Coimmunoprecipitation studies confirmed the interaction between RBCK1 and hPXR when both were ectopically expressed in AD-293 cells. Domain mapping studies showed that the interaction between RBCK1 and hPXR involves all RBCK1 domains. We further demonstrate that RBCK1 ubiquitinates hPXR, and this may target hPXR for degradation by the ubiquitin-proteasome pathway. Simultaneous ectopic overexpression of RBCK1 and PXR decreased PXR levels in AD-293 cells, and this decrease was inhibited by the proteasomal inhibitor MG-132 (carbobenzoxy-Leu-Leu-leucinal). Furthermore, overexpression of RBCK1 decreased endogenous levels of PXR in HepG2 cells. Of importance, ectopic overexpression and silencing of endogenous RBCK1 in primary human hepatocytes resulted in a decrease and increase, respectively, in endogenous PXR protein levels and in the induction of PXR target genes by rifampicin. These results suggest that RBCK1 is important for the ubiquitination of PXR and may play a role in its proteasomal degradation.
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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.