Evidence map›Paper›PMID 26651153›Full record

ArticleMolecular pharmaceutics2016

An Essential Role of Nedd4-2 in the Ubiquitination, Expression, and Function of Organic Anion Transporter-3.

Da Xu, Haoxun Wang, Guofeng You

Open access · greenAbstract read
In one paragraph

Article in Molecular pharmaceutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.8field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 30 citations in OpenAlex.

  1. Review
  2. Article
  3. Renal Organic Anion Transporters 1 and 3 In Vitro: Gone but Not Forgotten.International journal of molecular sciences · 2023
    Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Exhaustive exercise decreases renal organic anion transporter 3 function.The journal of physiological sciences : JPS · 2019
    Article
  13. Article
  14. Post-translational modifications of transporters.Pharmacology & therapeutics · 2018
    Review
  15. Article
  16. Article
  17. PKC/Nedd4-2 Signaling Pathway Regulates the Cell Surface Expression of Drug Transporter hOAT1.Drug metabolism and disposition: the biological fate of chemicals · 2017
    Article
  18. Review
  19. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Da XuDepartment of Pharmaceutics, Rutgers University , Piscataway, New Jersey 08854, United States.
Haoxun WangDepartment of Pharmaceutics, Rutgers University , Piscataway, New Jersey 08854, United States.
Guofeng YouDepartment of Pharmaceutics, Rutgers University , Piscataway, New Jersey 08854, United States.
Rutgers, The State University of New Jersey · US

Funding

Sumoylation: A Novel Mechanism for Regulating Drug/Xenobiotic Transporters OATsR01GM097000 · NIGMS · RUTGERS, THE STATE UNIV OF N.J. · PI YOU, GUOFENG · 2012 to 2020
$2.4M
Trafficking and Regulation of Drug/Xenobiotic Transporter OATR01GM079123 · NIGMS · RUTGERS, THE STATE UNIV OF N.J. · PI YOU, GUOFENG · 2008 to 2017
$2.2M
NIGMS NIH HHS R01 GM079123NIGMS NIH HHS R01-GM079123NIGMS NIH HHS R01 GM097000NIGMS NIH HHS R01-GM097000
6 · The paper itself

Abstract

Organic anion transporter-3 (OAT3) is a member of the organic anion transporter family that mediates the body disposition of a diverse array of clinically important drugs. We previously demonstrated that activation of protein kinase C (PKC) inhibits OAT3 transport activity by accelerating OAT3 internalization from cell surface into intracellular compartments. In the current study, we established that PKC-induced inhibition of OAT3 transport activity occurred through an enhanced OAT3 ubiquitination, a process catalyzed by an E3 ubiquitin-protein ligase Nedd4-2 (neural precursor cell expressed, developmentally downregulated 4-2). Overexpression of Nedd4-2 enhanced OAT3 ubiquitination, decreased OAT3 expression at the cell surface, and inhibited OAT3 transport activity. In contrast, overexpression of the ubiquitin ligase-dead mutant Nedd4-2/C821A or siRNA knockdown of endogenous Nedd4-2 had opposite effects on OAT3. Furthermore, immunoprecipitation experiments conducted both in culture cells and with rat kidney slices showed that there was a physical interaction between OAT3 and Nedd4-2. In conclusion, our results provided the first evidence that Nedd4-2 is an important regulator for OAT3 ubiquitination, expression, and transport activity.

Indexed as

AnimalsChlorocebus aethiopsCOS CellsEndocytosisEndosomal Sorting Complexes Required for TransportHEK293 CellsHumansImmunoblottingImmunoprecipitationKidneyMaleNedd4 Ubiquitin Protein LigasesOrganic Anion Transporters, Sodium-IndependentProtein Kinase CProtein TransportRatsEndosomal Sorting Complexes Required for TransportNedd4L protein, humanNEDD4L protein, ratNedd4 protein, humanNedd4 protein, ratNedd4 Ubiquitin Protein LigasesOrganic Anion Transporters, Sodium-Independentorganic anion transport protein 3Protein Kinase CUbiquitinUbiquitin-Protein Ligasesdrug transportermembrane transporterregulationubiquitinationubiquitin ligase

Identifiers

PMID26651153
PMCPMC5175273
OpenAlexW2283153124

What OpenQuestion holds

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Registered trials

None linked

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.