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Am J Physiol Lung Cell Mol Physiol
2012 Oct 15;3038:L720-7. doi: 10.1152/ajplung.00409.2011.
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Nedd4-2 does not regulate wt-CFTR in human airway epithelial cells.
Koeppen K
,
Chapline C
,
Sato JD
,
Stanton BA
.
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The cystic fibrosis transmembrane conductance regulator (CFTR), a Cl(-) channel in airway epithelial cells, plays an important role in maintaining the volume of the airway surface liquid and therefore mucociliary clearance of respiratory pathogens. A recent study has shown that the E3 ubiquitin ligase Neural precursor cells expressed developmentally downregulated (Nedd4-2) ubiquitinates ΔF508-CFTR in pancreatic epithelial cells and that siRNA-mediated silencing of Nedd4-2 increases plasma membrane ΔF508-CFTR. Because the role of Nedd4-2 in regulating wild-type (wt)-CFTR in airway epithelial cells is unknown, studies were conducted to test the hypothesis that Nedd4-2 also ubiquitinates wt-CFTR and regulates its plasma membrane abundance. We found that Nedd4-2 did not affect wt-CFTR Cl(-) currents in Xenopus oocytes. Likewise, overexpression of Nedd4-2 in human airway epithelial cells did not alter the amount of ubiquitinated wt-CFTR. siRNA knockdown of Nedd4-2 in human airway epithelial cells had no effect on ubiquitination or apical plasma membrane abundance of wt-CFTR. Thus Nedd4-2 does not ubiquitinate and thereby regulate wt-CFTR in human airway epithelial cells.
Albesa,
Nedd4-2-dependent ubiquitylation and regulation of the cardiac potassium channel hERG1.
2011, Pubmed
Albesa,
Nedd4-2-dependent ubiquitylation and regulation of the cardiac potassium channel hERG1.
2011,
Pubmed
Avella,
SLC26A9 stimulates CFTR expression and function in human bronchial cell lines.
2011,
Pubmed
,
Xenbase
Bebok,
Failure of cAMP agonists to activate rescued deltaF508 CFTR in CFBE41o- airway epithelial monolayers.
2005,
Pubmed
Bomberger,
The deubiquitinating enzyme USP10 regulates the post-endocytic sorting of cystic fibrosis transmembrane conductance regulator in airway epithelial cells.
2009,
Pubmed
Bomberger,
A Pseudomonas aeruginosa toxin that hijacks the host ubiquitin proteolytic system.
2011,
Pubmed
Boucher,
New concepts of the pathogenesis of cystic fibrosis lung disease.
2004,
Pubmed
Caohuy,
Rescue of DeltaF508-CFTR by the SGK1/Nedd4-2 signaling pathway.
2009,
Pubmed
Chandran,
Neural precursor cell-expressed developmentally down-regulated protein 4-2 (Nedd4-2) regulation by 14-3-3 protein binding at canonical serum and glucocorticoid kinase 1 (SGK1) phosphorylation sites.
2011,
Pubmed
Chen,
NEDD4L on human chromosome 18q21 has multiple forms of transcripts and is a homologue of the mouse Nedd4-2 gene.
2001,
Pubmed
Ekberg,
Regulation of the voltage-gated K(+) channels KCNQ2/3 and KCNQ3/5 by ubiquitination. Novel role for Nedd4-2.
2007,
Pubmed
,
Xenbase
Foot,
Regulation of the divalent metal ion transporter DMT1 and iron homeostasis by a ubiquitin-dependent mechanism involving Ndfips and WWP2.
2008,
Pubmed
Guggino,
New insights into cystic fibrosis: molecular switches that regulate CFTR.
2006,
Pubmed
Harvey,
N4WBP5, a potential target for ubiquitination by the Nedd4 family of proteins, is a novel Golgi-associated protein.
2002,
Pubmed
Hryciw,
Nedd4-2 functionally interacts with ClC-5: involvement in constitutive albumin endocytosis in proximal tubule cells.
2004,
Pubmed
,
Xenbase
Jensen,
Multiple proteolytic systems, including the proteasome, contribute to CFTR processing.
1995,
Pubmed
Jolliffe,
Identification of multiple proteins expressed in murine embryos as binding partners for the WW domains of the ubiquitin-protein ligase Nedd4.
2000,
Pubmed
Kamynina,
Distinct characteristics of two human Nedd4 proteins with respect to epithelial Na(+) channel regulation.
2001,
Pubmed
,
Xenbase
Lee,
Dynamic regulation of cystic fibrosis transmembrane conductance regulator by competitive interactions of molecular adaptors.
2007,
Pubmed
Lisanti,
Steady-state distribution and biogenesis of endogenous Madin-Darby canine kidney glycoproteins: evidence for intracellular sorting and polarized cell surface delivery.
1989,
Pubmed
Moyer,
Membrane trafficking of the cystic fibrosis gene product, cystic fibrosis transmembrane conductance regulator, tagged with green fluorescent protein in madin-darby canine kidney cells.
1998,
Pubmed
Riordan,
Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA.
1989,
Pubmed
Sato,
Regulation of human cystic fibrosis transmembrane conductance regulator (CFTR) by serum- and glucocorticoid-inducible kinase (SGK1).
2007,
Pubmed
,
Xenbase
Shearwin-Whyatt,
N4WBP5A (Ndfip2), a Nedd4-interacting protein, localizes to multivesicular bodies and the Golgi, and has a potential role in protein trafficking.
2004,
Pubmed
,
Xenbase
Sudol,
NeW wrinkles for an old domain.
2000,
Pubmed
Talebian,
Corr4A and VRT325 do not reduce the inflammatory response to P. aeruginosa in human cystic fibrosis airway epithelial cells.
2009,
Pubmed
Yang,
Nedd4 and Nedd4-2: closely related ubiquitin-protein ligases with distinct physiological functions.
2010,
Pubmed
Zhang,
Down-regulation of intestinal apical calcium entry channel TRPV6 by ubiquitin E3 ligase Nedd4-2.
2010,
Pubmed
,
Xenbase
van Bemmelen,
Cardiac voltage-gated sodium channel Nav1.5 is regulated by Nedd4-2 mediated ubiquitination.
2004,
Pubmed
