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Genomes and Genes
Species | Nedd4lSummaryGene Symbol: Nedd4l Description: neural precursor cell expressed, developmentally down-regulated 4-like, E3 ubiquitin protein ligase Alias: Nedd4-2, E3 ubiquitin-protein ligase NEDD4-like Species: rat Products: Nedd4l Top Publications
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Publications
- Harvey K, Dinudom A, Cook D, Kumar S. The Nedd4-like protein KIAA0439 is a potential regulator of the epithelial sodium channel. J Biol Chem. 2001;276:8597-601 pubmed..We propose that KIAA0439 and Nedd4 proteins either play a redundant role in ENaC regulation or function in a tissue- and/or signal-specific manner to down-regulate ENaC. ..
- Xu D, Wang H, You G. An Essential Role of Nedd4-2 in the Ubiquitination, Expression, and Function of Organic Anion Transporter-3. Mol Pharm. 2016;13:621-30 pubmed publisher..In conclusion, our results provided the first evidence that Nedd4-2 is an important regulator for OAT3 ubiquitination, expression, and transport activity. ..
- Gille T, Randrianarison Pellan N, Goolaerts A, Dard N, Uzunhan Y, Ferrary E, et al. Hypoxia-induced inhibition of epithelial Na(+) channels in the lung. Role of Nedd4-2 and the ubiquitin-proteasome pathway. Am J Respir Cell Mol Biol. 2014;50:526-37 pubmed publisher..Our data strongly suggest that Nedd4-2-mediated ubiquitination of ENaC leading to endocytosis and degradation of apical Na(+) channels is a key feature of hypoxia-induced inhibition of transepithelial alveolar Na(+) transport. ..
- van Bemmelen M, Rougier J, Gavillet B, Apothéloz F, Daidié D, Tateyama M, et al. Cardiac voltage-gated sodium channel Nav1.5 is regulated by Nedd4-2 mediated ubiquitination. Circ Res. 2004;95:284-91 pubmed..5. These results demonstrate that Na(v)1.5 can be ubiquitinated in heart tissues and that the ubiquitin-protein ligase Nedd4-2 acts on Na(v)1.5 by decreasing the channel density at the cell surface. ..
- Kabra R, Knight K, Zhou R, Snyder P. Nedd4-2 induces endocytosis and degradation of proteolytically cleaved epithelial Na+ channels. J Biol Chem. 2008;283:6033-9 pubmed publisher..Together the data indicate that Nedd4-2 reduces ENaC surface expression by altering its trafficking at two distinct sites in the endocytic pathway, inducing endocytosis of cleaved channels and targeting them for degradation. ..
- Lee I, Dinudom A, Sanchez Perez A, Kumar S, Cook D. Akt mediates the effect of insulin on epithelial sodium channels by inhibiting Nedd4-2. J Biol Chem. 2007;282:29866-73 pubmed..Together these data suggest that both Akt and Sgk are components of an insulin signaling pathway that increases Na(+) absorption by up-regulating membrane expression of ENaC via a regulatory system that involves inhibition of Nedd4-2. ..
- Wilkars W, Wollberg J, Mohr E, Han M, Chetkovich D, Bähring R, et al. Nedd4-2 regulates surface expression and may affect N-glycosylation of hyperpolarization-activated cyclic nucleotide-gated (HCN)-1 channels. FASEB J. 2014;28:2177-90 pubmed publisher..Taken together, our data indicate that Nedd4-2 plays an important role in the regulation of HCN1 trafficking and may compete with TRIP8b(1a-4) in this process. ..
- Georgieva M, de Pablo Y, Sanchis D, Comella J, Llovera M. Ubiquitination of TrkA by Nedd4-2 regulates receptor lysosomal targeting and mediates receptor signaling. J Neurochem. 2011;117:479-93 pubmed publisher..In addition, TrkA multimonoubiquitination does not interfere with the activation of signaling cascades, but rather potentiates receptor signaling leading to differentiation. ..
- Kamynina E, Debonneville C, Bens M, Vandewalle A, Staub O. A novel mouse Nedd4 protein suppresses the activity of the epithelial Na+ channel. FASEB J. 2001;15:204-214 pubmed..Thus, these results suggest that the novel suppressor protein Nedd4-2 is the regulator of ENaC and hence a potential susceptibility gene for arterial hypertension. ..
- Albesa M, Grilo L, Gavillet B, Abriel H. Nedd4-2-dependent ubiquitylation and regulation of the cardiac potassium channel hERG1. J Mol Cell Cardiol. 2011;51:90-8 pubmed publisher..These results suggest that ubiquitylation of the hERG1 protein by Nedd4-2, and its subsequent down-regulation, could represent an important mechanism for modulation of the duration of the human cardiac action potential. ..
- Chan W, Tian R, Lee Y, Sit S, Lim L, Manser E. Down-regulation of active ACK1 is mediated by association with the E3 ubiquitin ligase Nedd4-2. J Biol Chem. 2009;284:8185-94 pubmed publisher..These processes are particularly pertinent given the report of genomic amplification of the ACK1 locus in metastatic tumors. ..
- Shi P, Cao X, Sweezer E, Kinney T, Williams N, Husted R, et al. Salt-sensitive hypertension and cardiac hypertrophy in mice deficient in the ubiquitin ligase Nedd4-2. Am J Physiol Renal Physiol. 2008;295:F462-70 pubmed publisher..The absence of this gene is sufficient to produce salt-sensitive hypertension. This model provides an opportunity to further investigate mechanisms and consequences of this common disorder. ..
- Li T, Koshy S, Folkesson H. Involvement of {alpha}ENaC and Nedd4-2 in the conversion from lung fluid secretion to fluid absorption at birth in the rat as assayed by RNA interference analysis. Am J Physiol Lung Cell Mol Physiol. 2007;293:L1069-78 pubmed..Thus we provide evidence that ENaC and Nedd4-2 are involved in the transition from lung fluid secretion to fluid absorption near term and at birth. ..
- Anta B, Martín Rodríguez C, Gomis Pèrez C, Calvo L, López Benito S, Calderón García A, et al. Ubiquitin-specific Protease 36 (USP36) Controls Neuronal Precursor Cell-expressed Developmentally Down-regulated 4-2 (Nedd4-2) Actions over the Neurotrophin Receptor TrkA and Potassium Voltage-gated Channels 7.2/3 (Kv7.2/3). J Biol Chem. 2016;291:19132-45 pubmed publisher..2/3 channel regulation. Our results demonstrate that USP36 binds to and regulates the actions of Nedd4-2 over different substrates affecting their expression and functions. ..
- Jespersen T, Membrez M, Nicolas C, Pitard B, Staub O, Olesen S, et al. The KCNQ1 potassium channel is down-regulated by ubiquitylating enzymes of the Nedd4/Nedd4-like family. Cardiovasc Res. 2007;74:64-74 pubmed..This mechanism may thereby be important in regulating the surface density of the KCNQ1 channels in cardiomyocytes and other cell types. ..
- Umemura M, Ishigami T, Tamura K, Sakai M, Miyagi Y, Nagahama K, et al. Transcriptional diversity and expression of NEDD4L gene in distal nephron. Biochem Biophys Res Commun. 2006;339:1129-37 pubmedThe ubiquitin ligase NEDD4L participates in plasma volume and blood pressure regulation by controlling expression of the epithelial sodium channel (ENaC)...