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
Da XuGuofeng You

Abstract

Human organic anion transporter 1 (hOAT1) expressed at the membrane of the kidney proximal tubule cells mediates the body disposition of a diverse array of clinically important drugs, including anti-HIV therapeutics, antitumor drugs, antibiotics, antihypertensives, and antiinflammatories. Therefore, understanding the regulation of hOAT1 will provide significant insights into kidney function and dysfunction. We previously established that hOAT1 transport activity is inhibited by activation of protein kinase C (PKC) through accelerating hOAT1 internalization from cell surface into intracellular endosomes and subsequent degradation. We further established that PKC-induced hOAT1 ubiquitination is an important step preceding hOAT1 internalization. In the current study, we identified two closely related E3 ubiquitin ligases, neural precursor cell expressed, developmentally downregulated 4-1 and 4-2 (Nedd4-1 and Nedd4-2), as important regulators for hOAT1: overexpression of Nedd4-1 or Nedd4-2 enhanced hOAT1 ubiquitination, reduced the hOAT1 amount at the cell surface, and suppressed hOAT1 transport activity. In further exploring the relationship among PKC, Nedd4-1, and Nedd4-2, we discovered that PKC-dependent changes in hOAT1 ubiquit...Continue Reading

References

Feb 12, 1998·The American Journal of Physiology·D S Miller
Feb 8, 2000·American Journal of Physiology. Renal Physiology·A ShuprishaW H Dantzler
May 22, 2001·Archives of Biochemistry and Biophysics·M G KazanietzS Nowicki
Dec 14, 2001·American Journal of Physiology. Lung Cellular and Molecular Physiology·B R CobbJ P Clancy
Jun 13, 2002·American Journal of Physiology. Renal Physiology·Xiaohong ZhangStephen H Wright
Oct 9, 2002·Medicinal Research Reviews·Guofeng You
Oct 10, 2002·American Journal of Physiology. Renal Physiology·Saulo Klahr, Jeremiah Morrissey
Nov 9, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Andrew B FotiaSharad Kumar
Jul 23, 2003·Journal of the American Society of Nephrology : JASN·Natascha A WolffGerhard Burckhardt
Dec 3, 2003·The Journal of Biological Chemistry·Peter M SnyderDiane R Olson
Apr 9, 2005·American Journal of Physiology. Renal Physiology·Omar A ItaniChristie P Thomas
Dec 1, 2005·Kidney International·Silvina R VillarAdriana M Torres
Apr 8, 2006·Physiological Reviews·Olivier Staub, Daniela Rotin
Jul 15, 2006·Archives of Biochemistry and Biophysics·Kazuhiko NagaiSoichi Miwa
Aug 4, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Tatiana SorkinaAlexander Sorkin
Sep 28, 2006·The Journal of Biological Chemistry·Takahiro HatanakaMitsutoshi Setou
Dec 2, 2006·Biochemical Pharmacology·Tomohiro Terada, Ken-ichi Inui
May 16, 2007·The Journal of Biological Chemistry·Ruifeng ZhouPeter M Snyder
Jun 12, 2008·The Journal of Biological Chemistry·Sudha K ShenoyAllan M Weissman
Dec 3, 2009·Molecular Systems Biology·Avinash PersaudDaniela Rotin
Sep 22, 2010·The Journal of Biological Chemistry·Alexandre Simonin, Daniel Fuster
Jan 8, 2011·The Journal of Biological Chemistry·Arnau Vina-VilasecaAlexander Sorkin
Apr 22, 2014·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Kazuya MaedaYuichi Sugiyama
Oct 3, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Raymond Wong, Lyanne C Schlichter
Nov 2, 2014·Archives of Pharmacal Research·Mihwa KwonIm-Sook Song
Oct 23, 2015·Clinical Journal of the American Society of Nephrology : CJASN·Sanjay K NigamVibha Bhatnagar

❮ Previous
Next ❯

Citations

Jun 3, 2017·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Da XuGuofeng You
Jun 14, 2017·Biopharmaceutics & Drug Disposition·Haoxun Wang, Guofeng You
Mar 23, 2021·Expert Opinion on Drug Metabolism & Toxicology·Adriana M TorresSanjay K Nigam
May 7, 2021·The Journal of Veterinary Medical Science·Keisuke ImotoHideyuki Yamawaki

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antihypertensive Agents: Mechanisms of Action

Antihypertensive drugs are used to treat hypertension (high blood pressure) which aims to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Discover the latest research on antihypertensive drugs and their mechanism of action here.

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.