ArticleMolecular pharmacology2013
Three ubiquitination sites of organic anion transporter-1 synergistically mediate protein kinase C-dependent endocytosis of the transporter.
Article in Molecular pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Renal organic anion transporter 1: clinical relevance and the underlying mechanisms in chronic kidney disease.BMC nephrology · 2025Review
- Ubiquitination is involved in PKC-mediated degradation of cell surface Kv1.5 channels.The Journal of biological chemistry · 2024Article
- Renal Organic Anion Transporters 1 and 3 In Vitro: Gone but Not Forgotten.International journal of molecular sciences · 2023Review
- The structural context of posttranslational modifications at a proteome-wide scale.PLoS biology · 2022Article
- Protein kinase C regulates organic anion transporter 1 through phosphorylating ubiquitin ligase Nedd4-2.BMC molecular and cell biology · 2021Article
- Regulation of organic anion transporters: Role in physiology, pathophysiology, and drug elimination.Pharmacology & therapeutics · 2021Review
- Post-translational regulation of the major drug transporters in the families of organic anion transporters and organic anion-transporting polypeptides.The Journal of biological chemistry · 2020Review
- The SUMO-Specific Protease Senp2 Regulates SUMOylation, Expression and Function of Human Organic Anion Transporter 3.Biochimica et biophysica acta. Biomembranes · 2019Article
- Post-translational modifications of transporters.Pharmacology & therapeutics · 2018Review
- Disease-Associated Changes in Drug Transporters May Impact the Pharmacokinetics and/or Toxicity of Drugs: A White Paper From the International Transporter Consortium.Clinical pharmacology and therapeutics · 2018Article
- Trafficking and other regulatory mechanisms for organic anion transporting polypeptides and organic anion transporters that modulate cellular drug and xenobiotic influx and that are dysregulated in disease.British journal of pharmacology · 2017Review
- Loops and layers of post-translational modifications of drug transporters.Advanced drug delivery reviews · 2017Review
- Cetuximab Prevents Methotrexate-Induced Cytotoxicity in Vitro through Epidermal Growth Factor Dependent Regulation of Renal Drug Transporters.Molecular pharmaceutics · 2017Article
- Protein Kinases C-Mediated Regulations of Drug Transporter Activity, Localization and Expression.International journal of molecular sciences · 2017Review
- Posttranslational Regulation of Organic Anion Transporters by Ubiquitination: Known and Novel.Medicinal research reviews · 2016Review
- The role of Nedd4-1 WW domains in binding and regulating human organic anion transporter 1.American journal of physiology. Renal physiology · 2016Article
- Nedd4-2 but not Nedd4-1 is critical for protein kinase C-regulated ubiquitination, expression, and transport activity of human organic anion transporter 1.American journal of physiology. Renal physiology · 2016Article
- Post-endocytotic Deubiquitination and Degradation of the Metabotropic γ-Aminobutyric Acid Receptor by the Ubiquitin-specific Protease 14.The Journal of biological chemistry · 2016Article
- The organic anion transporter (OAT) family: a systems biology perspective.Physiological reviews · 2015Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Organic anion transporter-1 (OAT1) mediates the body disposition of a diverse array of clinically important drugs, including anti-HIV therapeutics, antitumor drugs, antibiotics, antihypertensives, and anti-inflammatories. Therefore, understanding the regulation of OAT1 has profound clinical significance. We previously established that OAT1 constitutively internalizes from and recycles back to cell surface and that activation of protein kinase C (PKC) inhibits OAT1 activity by promoting ubiquitination of the transporter, which then leads to an accelerated internalization of the transporter from cell surface to intracellular compartments. In the current study, we showed that PKC isoform PKCα was responsible for OAT1 ubiquitination. To directly address the role of OAT1 ubiquitination, we then generated two OAT1 mutants, each having multiple lysines (K) simultaneously mutated to arginine (R). One mutant K163/297/303/315/321R lost sensitivities to PKC-induced inhibition of transport activity, to PKC-induced ubiquitination, and to PKC-induced acceleration of transporter internalization. Further dissecting each lysine in this mutant, we identified Lys297, Lys303, and Lys315 as being the ubiquitin conjugation sites. Of interest, mutating any one of the three lysines prevented the ubiquitin conjugation to the other two lysines, suggesting that Lys297, Lys303, and Lys315 may form an optimal structure to interact with ubiquitination machineries. This is the first demonstration that Lys297, Lys303, and Lys315 play a synergistic role in PKC-regulated OAT1 ubiquitination, trafficking, and transport activity.
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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.