NEDD4

Summary

Gene Symbol: NEDD4
Description: neural precursor cell expressed, developmentally down-regulated 4, E3 ubiquitin protein ligase
Alias: NEDD4-1, RPF1, E3 ubiquitin-protein ligase NEDD4, HECT-type E3 ubiquitin transferase NEDD4, cell proliferation-inducing gene 53 protein, receptor-potentiating factor 1
Species: human
Products:     NEDD4

Top Publications

  1. Farr T, Coddington Lawson S, Snyder P, McDonald F. Human Nedd4 interacts with the human epithelial Na+ channel: WW3 but not WW1 binds to Na+-channel subunits. Biochem J. 2000;345 Pt 3:503-9 pubmed
    ..Here we report the identification of this protein as human Nedd4, a ubiquitin-protein ligase that binds to the Na(+)-channel subunits via its WW domains...
  2. Vecchione A, Marchese A, Henry P, Rotin D, Morrione A. The Grb10/Nedd4 complex regulates ligand-induced ubiquitination and stability of the insulin-like growth factor I receptor. Mol Cell Biol. 2003;23:3363-72 pubmed
    ..J. Biol. Chem. 272:26382-26387, 1997). With mGrb10alpha as bait in a yeast two-hybrid screen, mouse Nedd4 (mNedd4-1), a ubiquitin protein ligase, was previously isolated as an interacting protein of Grb10 (A...
  3. Amodio N, Scrima M, Palaia L, Salman A, Quintiero A, Franco R, et al. Oncogenic role of the E3 ubiquitin ligase NEDD4-1, a PTEN negative regulator, in non-small-cell lung carcinomas. Am J Pathol. 2010;177:2622-34 pubmed publisher
    ..Since recent reports implicated neural precursor cell expressed, developmentally down-regulated 4-1 (NEDD4-1) as the E3 ubiquitin ligase that regulates PTEN stability, we investigated the role of NEDD4-1 in the regulation ..
  4. Shenoy S, Xiao K, Venkataramanan V, Snyder P, Freedman N, Weissman A. Nedd4 mediates agonist-dependent ubiquitination, lysosomal targeting, and degradation of the beta2-adrenergic receptor. J Biol Chem. 2008;283:22166-76 pubmed publisher
    ..Among the various catalytically inactive E3 ubiquitin ligase mutants that we tested, a dominant negative Nedd4 specifically inhibited isoproterenol-induced ubiquitination and degradation of the beta(2)AR in HEK-293 cells...
  5. Plant P, Correa J, Goldenberg N, Bain J, Batt J. The inositol phosphatase MTMR4 is a novel target of the ubiquitin ligase Nedd4. Biochem J. 2009;419:57-63 pubmed publisher
    ..phosphatase, MTMR4 (myotubularin-related protein 4), was identified as a novel interactor of the ubiquitin ligase Nedd4 (neural-precursor-cell-expressed developmentally down-regulated 4)...
  6. Eide P, Cekaite L, Danielsen S, Eilertsen I, Kjenseth A, Fykerud T, et al. NEDD4 is overexpressed in colorectal cancer and promotes colonic cell growth independently of the PI3K/PTEN/AKT pathway. Cell Signal. 2013;25:12-8 pubmed publisher
    ..Among the significantly overexpressed genes was NEDD4 (neural precursor cell-expressed developmentally down-regulated 4), the prototype member of the HECT (homologous ..
  7. Polo S, Sigismund S, Faretta M, Guidi M, Capua M, Bossi G, et al. A single motif responsible for ubiquitin recognition and monoubiquitination in endocytic proteins. Nature. 2002;416:451-5 pubmed
    ..In addition, through their own ubiquitination, they may further contribute to the amplification of this network in the endocytic pathway. ..
  8. Donovan P, Poronnik P. Nedd4 and Nedd4-2: ubiquitin ligases at work in the neuron. Int J Biochem Cell Biol. 2013;45:706-10 pubmed publisher
    Ubiquitination of proteins by the Nedd4 family of ubiquitin ligases is a significant mechanism in protein trafficking and degradation and provides for tight spatiotemporal regulation...
  9. Snyder P, Steines J, Olson D. Relative contribution of Nedd4 and Nedd4-2 to ENaC regulation in epithelia determined by RNA interference. J Biol Chem. 2004;279:5042-6 pubmed
    ..b>Nedd4 and Nedd4-2 are candidates to control ENaC surface expression, but it is not known which of these proteins ..

More Information

Publications85

  1. Lu P, Zhou X, Shen M, Lu K. Function of WW domains as phosphoserine- or phosphothreonine-binding modules. Science. 1999;283:1325-8 pubmed
    ..WW domains of the essential mitotic prolyl isomerase Pin1 and the ubiquitin ligase Nedd4 bound to phosphoproteins, including physiological substrates of enzymes, in a phosphorylation-dependent manner...
  2. Schwarz L, Hall B, Patrick G. Activity-dependent ubiquitination of GluA1 mediates a distinct AMPA receptor endocytosis and sorting pathway. J Neurosci. 2010;30:16718-29 pubmed publisher
    ..Through overexpression or RNA interference-mediated knockdown, we identify that a specific E3 ligase, Nedd4-1 (neural-precursor cell-expressed developmentally downregulated gene 4-1), is necessary for this process...
  3. Sette P, Jadwin J, Dussupt V, Bello N, Bouamr F. The ESCRT-associated protein Alix recruits the ubiquitin ligase Nedd4-1 to facilitate HIV-1 release through the LYPXnL L domain motif. J Virol. 2010;84:8181-92 pubmed publisher
    ..gain access to the host ESCRT components by utilizing a PPXY-type L domain that interacts with cellular Nedd4-like ubiquitin ligases...
  4. Dai B, Pieper R, Li D, Wei P, Liu M, Woo S, et al. FoxM1B regulates NEDD4-1 expression, leading to cellular transformation and full malignant phenotype in immortalized human astrocytes. Cancer Res. 2010;70:2951-61 pubmed publisher
    ..Mechanistically, our results showed that overexpression of FoxM1B upregulated NEDD4-1, an E3 ligase that mediates the degradation and downregulation of phosphatase and tensin homologue (PTEN) in ..
  5. Anan T, Nagata Y, Koga H, Honda Y, Yabuki N, Miyamoto C, et al. Human ubiquitin-protein ligase Nedd4: expression, subcellular localization and selective interaction with ubiquitin-conjugating enzymes. Genes Cells. 1998;3:751-63 pubmed
    b>Nedd4 is a ubiquitin-protein ligase containing a calcium/lipid-binding domain, multiple WW domains and a C-terminal Hect domain, which is required for both the ubiquitin transfer and the association with E2 ubiquitin-conjugating enzymes...
  6. Simonin A, Fuster D. Nedd4-1 and beta-arrestin-1 are key regulators of Na+/H+ exchanger 1 ubiquitylation, endocytosis, and function. J Biol Chem. 2010;285:38293-303 pubmed publisher
    ..This process requires the adapter protein ?-arrestin-1 that interacts with both the E3 ubiquitin ligase Nedd4-1 and the NHE1 C terminus...
  7. 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
    ..The C-terminal tail of TrkA contains a PPXY motif, the binding site of the E3 ubiquitin-ligase Nedd4-2 (neural precursor cell expressed, developmentally down-regulated 4-2)...
  8. Pak Y, Glowacka W, Bruce M, Pham N, Rotin D. Transport of LAPTM5 to lysosomes requires association with the ubiquitin ligase Nedd4, but not LAPTM5 ubiquitination. J Cell Biol. 2006;175:631-45 pubmed
    ..We show that LAPTM5 binds the ubiquitin-ligase Nedd4 and GGA3 to promote LAPTM5 sorting from the Golgi to the lysosome, an event that is independent of LAPTM5 ..
  9. Anindya R, Aygün O, Svejstrup J. Damage-induced ubiquitylation of human RNA polymerase II by the ubiquitin ligase Nedd4, but not Cockayne syndrome proteins or BRCA1. Mol Cell. 2007;28:386-97 pubmed
    ..Instead, we identified Nedd4 as an E3 that associates with and ubiquitylates RNAPII in response to UV-induced DNA damage in human cells...
  10. Snyder P, Olson D, McDonald F, Bucher D. Multiple WW domains, but not the C2 domain, are required for inhibition of the epithelial Na+ channel by human Nedd4. J Biol Chem. 2001;276:28321-6 pubmed
    ..The activity of ENaC is controlled by its interaction with Nedd4; mutations that disrupt this interaction increase Na+ absorption, causing an inherited form of hypertension (..
  11. Zeng F, Xu J, Harris R. Nedd4 mediates ErbB4 JM-a/CYT-1 ICD ubiquitination and degradation in MDCK II cells. FASEB J. 2009;23:1935-45 pubmed publisher
    ..Further studies implicated Nedd4, an E3 ubiquitin ligase, as a mediator of CYT-1 ubiquitination and degradation...
  12. Ushijima Y, Koshizuka T, Goshima F, Kimura H, Nishiyama Y. Herpes simplex virus type 2 UL56 interacts with the ubiquitin ligase Nedd4 and increases its ubiquitination. J Virol. 2008;82:5220-33 pubmed publisher
    ..UL56 interacts with KIF1A and UL11. Here we report that UL56 also interacts with the ubiquitin ligase Nedd4 and increases its ubiquitination. Nedd4 was identified as a UL56-interacting protein by a yeast two-hybrid screen...
  13. Trotman L, Wang X, Alimonti A, Chen Z, Teruya Feldstein J, Yang H, et al. Ubiquitination regulates PTEN nuclear import and tumor suppression. Cell. 2007;128:141-56 pubmed
  14. Staub O, Gautschi I, Ishikawa T, Breitschopf K, Ciechanover A, Schild L, et al. Regulation of stability and function of the epithelial Na+ channel (ENaC) by ubiquitination. EMBO J. 1997;16:6325-36 pubmed
    ..We have recently identified the ubiquitin-protein ligase Nedd4 as an interacting protein of ENaC...
  15. Persaud A, Alberts P, Amsen E, Xiong X, Wasmuth J, Saadon Z, et al. Comparison of substrate specificity of the ubiquitin ligases Nedd4 and Nedd4-2 using proteome arrays. Mol Syst Biol. 2009;5:333 pubmed publisher
    Target recognition by the ubiquitin system is mediated by E3 ubiquitin ligases. Nedd4 family members are E3 ligases comprised of a C2 domain, 2-4 WW domains that bind PY motifs (L/PPxY) and a ubiquitin ligase HECT domain...
  16. Bruce M, Kanelis V, Fouladkou F, Debonneville A, Staub O, Rotin D. Regulation of Nedd4-2 self-ubiquitination and stability by a PY motif located within its HECT-domain. Biochem J. 2008;415:155-63 pubmed publisher
    ..b>Nedd4 (neural-precursor-cell-expressed, developmentally down-regulated 4)-2 is an E3 ubiquitin ligase composed of a C2 ..
  17. Ahn Y, Hwang C, Lee S, Kwon K, Lee C. The tumour suppressor PTEN mediates a negative regulation of the E3 ubiquitin-protein ligase Nedd4. Biochem J. 2008;412:331-8 pubmed publisher
    ..Among the proteins identified, we concentrated on the E3 ubiquitin-protein ligase Nedd4 (neural-precursor-cell-expressed, developmentally down-regulated gene 4), and performed subsequent validation ..
  18. Hong S, Moon J, Kim J, Shin J, Jung K, Lee W, et al. p34 is a novel regulator of the oncogenic behavior of NEDD4-1 and PTEN. Cell Death Differ. 2014;21:146-60 pubmed publisher
    PTEN is one of the most frequently mutated or deleted tumor suppressors in human cancers. NEDD4-1 was recently identified as the E3 ubiquitin ligase for PTEN; however, a number of important questions remain regarding the role of ..
  19. Lin Q, Wang J, Childress C, Sudol M, Carey D, Yang W. HECT E3 ubiquitin ligase Nedd4-1 ubiquitinates ACK and regulates epidermal growth factor (EGF)-induced degradation of EGF receptor and ACK. Mol Cell Biol. 2010;30:1541-54 pubmed publisher
    ..Here we report that ACK is ubiquitinated by HECT E3 ubiquitin ligase Nedd4-1 and degraded along with EGFR in response to EGF stimulation...
  20. Fan C, Lum M, Xu C, Black J, Wang X. Ubiquitin-dependent regulation of phospho-AKT dynamics by the ubiquitin E3 ligase, NEDD4-1, in the insulin-like growth factor-1 response. J Biol Chem. 2013;288:1674-84 pubmed publisher
    ..Here we show that NEDD4-1 is a novel E3 ligase that specifically regulates ubiquitin-dependent trafficking of pAKT in insulin-like growth ..
  21. Shearwin Whyatt L, Brown D, Wylie F, Stow J, Kumar S. N4WBP5A (Ndfip2), a Nedd4-interacting protein, localizes to multivesicular bodies and the Golgi, and has a potential role in protein trafficking. J Cell Sci. 2004;117:3679-89 pubmed
    N4WBP5A (Ndfip2) belongs to an evolutionarily conserved group of Nedd4-interacting proteins with two homologues in mammalian species...
  22. Blot V, Perugi F, Gay B, Pr vost M, Briant L, Tangy F, et al. Nedd4.1-mediated ubiquitination and subsequent recruitment of Tsg101 ensure HTLV-1 Gag trafficking towards the multivesicular body pathway prior to virus budding. J Cell Sci. 2004;117:2357-67 pubmed publisher
    ..The Gag proteins of oncoretroviruses possess a PPxY motif that recruits a ubiquitin ligase from the Nedd4 family, whereas those of the human immunodeficiency virus interact through a PTAP motif with Tsg101, a protein of ..
  23. Harvey K, Harvey N, Michael J, Parasivam G, Waterhouse N, Alnemri E, et al. Caspase-mediated cleavage of the ubiquitin-protein ligase Nedd4 during apoptosis. J Biol Chem. 1998;273:13524-30 pubmed
    ..Here we show that Nedd4, a ubiquitin-protein ligase containing multiple WW domains and a calcium/lipid-binding domain, is also cleaved ..
  24. Bouamr F, Melillo J, Wang M, Nagashima K, de Los Santos M, Rein A, et al. PPPYVEPTAP motif is the late domain of human T-cell leukemia virus type 1 Gag and mediates its functional interaction with cellular proteins Nedd4 and Tsg101 [corrected]. J Virol. 2003;77:11882-95 pubmed
    ..Two-hybrid and in vitro binding assays showed that the HTLV-1 Gag polyprotein binds both Tsg101 and Nedd4 proteins...
  25. Pham N, Rotin D. Nedd4 regulates ubiquitination and stability of the guanine-nucleotide exchange factor CNrasGEF. J Biol Chem. 2001;276:46995-7003 pubmed
    Cyclic nucleotide ras GEF (CNrasGEF) is a guanine-nucleotide exchange factor previously isolated in a screen for Nedd4-WW domain interacting proteins (Pham, N., Cheglakov, I., Koch, C. A., de Hoog, C. L., Moran, M. F., and Rotin, D...
  26. Harvey K, Shearwin Whyatt L, Fotia A, Parton R, Kumar S. N4WBP5, a potential target for ubiquitination by the Nedd4 family of proteins, is a novel Golgi-associated protein. J Biol Chem. 2002;277:9307-17 pubmed
    b>Nedd4 belongs to a family of ubiquitin-protein ligases that is characterized by 2--4 WW domains, a carboxyl-terminal Hect (homologous to E6-AP Carboxyl terminus)domain and in most cases an amino-terminal C2 domain...
  27. 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
    ..PPxY, motif which is believed to be important for interaction with the WW domains of the ubiquitin-protein ligase, Nedd4. Disruption of this interaction, as in Liddle's syndrome, where mutations delete or alter the PPxY motif of either ..
  28. Ott D, Coren L, Copeland T, Kane B, Johnson D, Sowder R, et al. Ubiquitin is covalently attached to the p6Gag proteins of human immunodeficiency virus type 1 and simian immunodeficiency virus and to the p12Gag protein of Moloney murine leukemia virus. J Virol. 1998;72:2962-8 pubmed
    ..These results show that ubiquitination of Gag is conserved among these retroviruses and occurs in the p6Gag portion of the Gag polyprotein, a region that is likely to be involved in assembly and budding. ..
  29. Aoh Q, Castle A, Hubbard C, Katsumata O, Castle J. SCAMP3 negatively regulates epidermal growth factor receptor degradation and promotes receptor recycling. Mol Biol Cell. 2009;20:1816-32 pubmed publisher
    ..SCAMP3 is multimonoubiquitylated and is able to associate with Nedd4 HECT ubiquitin ligases and the ESCRT-I subunit Tsg101 via its PY and PSAP motifs, respectively...
  30. Chandrasekaran P, Buckley M, Moore V, Wang L, Kehrl J, Venkatesan S. HIV-1 Nef impairs heterotrimeric G-protein signaling by targeting G?(i2) for degradation through ubiquitination. J Biol Chem. 2012;287:41481-98 pubmed publisher
    ..of G?(i2) loss and a partial recovery of impaired chemotaxis occurred following siRNA knockdown of AIP4 or NEDD4 or by inhibiting dynamin...
  31. Yang Z, Yuan X, Chen J, Lu N. Is NEDD4-1 a negative regulator of phosphatase and tensin homolog in gastric carcinogenesis?. World J Gastroenterol. 2012;18:6345-8 pubmed publisher
    ..While neuronal precursor cell-expressed developmentally down-regulated 4-1 (NEDD4-1) is believed to be a potential dual regulator of PTEN, there are conflicting reports regarding their interaction...
  32. Konstas A, Shearwin Whyatt L, Fotia A, Degger B, Riccardi D, Cook D, et al. Regulation of the epithelial sodium channel by N4WBP5A, a novel Nedd4/Nedd4-2-interacting protein. J Biol Chem. 2002;277:29406-16 pubmed
    ..PPXY motif that is believed to be important for interaction with the WW domains of the ubiquitin-protein ligases, Nedd4 and Nedd4-2...
  33. Katz M, Shtiegman K, Tal Or P, Yakir L, Mosesson Y, Harari D, et al. Ligand-independent degradation of epidermal growth factor receptor involves receptor ubiquitylation and Hgs, an adaptor whose ubiquitin-interacting motif targets ubiquitylation by Nedd4. Traffic. 2002;3:740-51 pubmed
    ..is endowed with two functions: it binds ubiquitylated proteins and it targets self-ubiquitylation by recruiting Nedd4, an ubiquitin ligase previously implicated in endocytosis...
  34. Asher C, Sinha I, Garty H. Characterization of the interactions between Nedd4-2, ENaC, and sgk-1 using surface plasmon resonance. Biochim Biophys Acta. 2003;1612:59-64 pubmed
    Previous studies have characterized interactions between the ubiquitin ligase Nedd4-1 and the epithelial Na(+) channel (ENaC). Such interactions control the channel cell surface expression and activity...
  35. Persaud A, Alberts P, Hayes M, Guettler S, Clarke I, Sicheri F, et al. Nedd4-1 binds and ubiquitylates activated FGFR1 to control its endocytosis and function. EMBO J. 2011;30:3259-73 pubmed publisher
    ..Here, we show that human Nedd4 (Nedd4-1), an E3 ubiquitin ligase comprised of a C2 domain, 4 WW domains, and a Hect domain, regulates endocytosis ..
  36. 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
    ..Here we demonstrate that KCNQ1 proteins expressed in HEK293 cells are down-regulated by Nedd4/Nedd4-like ubiquitin-protein ligases...
  37. Maspero E, Valentini E, Mari S, Cecatiello V, Soffientini P, Pasqualato S, et al. Structure of a ubiquitin-loaded HECT ligase reveals the molecular basis for catalytic priming. Nat Struct Mol Biol. 2013;20:696-701 pubmed publisher
    ..knowledge, of a Ub-loaded E3, the human neural precursor cell-expressed developmentally downregulated protein 4 (Nedd4)...
  38. Nakashima M, Chung S, Takahashi A, Kamatani N, Kawaguchi T, Tsunoda T, et al. A genome-wide association study identifies four susceptibility loci for keloid in the Japanese population. Nat Genet. 2010;42:768-71 pubmed publisher
    ..87) and rs940187 in another LD block with P = 1.80 x 10(-13) (OR = 1.98). Association of rs8032158 located in NEDD4 on chromosome 15 yielded P = 5.96 x 10(-13) (OR = 1.51)...
  39. Medina G, Zhang Y, Tang Y, Gottwein E, Vana M, Bouamr F, et al. The functionally exchangeable L domains in RSV and HIV-1 Gag direct particle release through pathways linked by Tsg101. Traffic. 2005;6:880-94 pubmed publisher
    The functionally exchangeable L domains of HIV-1 and Rous sarcoma virus (RSV) Gag bind Tsg101 and Nedd4, respectively...
  40. Kawabe H, Neeb A, Dimova K, Young S, Takeda M, Katsurabayashi S, et al. Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite development. Neuron. 2010;65:358-72 pubmed publisher
    b>Nedd4-1 is a "neuronal precursor cell expressed and developmentally downregulated protein" and among the most abundant E3 ubiquitin ligases in mammalian neurons...
  41. Kamynina E, Tauxe C, Staub O. Distinct characteristics of two human Nedd4 proteins with respect to epithelial Na(+) channel regulation. Am J Physiol Renal Physiol. 2001;281:F469-77 pubmed
    ..Taken together, our data demonstrate that hNedd4-2 inhibits ENaC, implying that this protein is a modulator of salt homeostasis, whereas hNedd4-1 is not primarily involved in ENaC regulation...
  42. Lin A, Hou Q, Jarzylo L, Amato S, Gilbert J, Shang F, et al. Nedd4-mediated AMPA receptor ubiquitination regulates receptor turnover and trafficking. J Neurochem. 2011;119:27-39 pubmed publisher
    ..We also find that the E3 ligase neural precursor cell expressed, developmentally down-regulated 4 (Nedd4) is enriched in synaptosomes and co-localizes and associates with AMPARs in neurons...
  43. Dordor A, Poudevigne E, Gottlinger H, Weissenhorn W. Essential and supporting host cell factors for HIV-1 budding. Future Microbiol. 2011;6:1159-70 pubmed publisher
    ..Here we review recent advances in understanding the role of host cell factors recruited by Gag during HIV-1 assembly and budding. ..
  44. Kwak Y, Wang B, Li J, Wang R, Deng Q, Diao S, et al. Upregulation of the E3 ligase NEDD4-1 by oxidative stress degrades IGF-1 receptor protein in neurodegeneration. J Neurosci. 2012;32:10971-81 pubmed
    The importance of ubiquitin E3 ligases in neurodegeneration is being increasingly recognized. The crucial role of NEDD4-1 in neural development is well appreciated; however, its role in neurodegeneration remains unexplored...
  45. Nabhan J, Pan H, Lu Q. Arrestin domain-containing protein 3 recruits the NEDD4 E3 ligase to mediate ubiquitination of the beta2-adrenergic receptor. EMBO Rep. 2010;11:605-11 pubmed publisher
    ..The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor...
  46. Plant P, Yeger H, Staub O, Howard P, Rotin D. The C2 domain of the ubiquitin protein ligase Nedd4 mediates Ca2+-dependent plasma membrane localization. J Biol Chem. 1997;272:32329-36 pubmed
    Neuronal precursor cell-expressed developmentally down-regulated 4 (Nedd4) is a ubiquitin protein ligase (E3) containing a hect domain, 3 or 4 WW domains, and a putative C2 domain...
  47. French M, Kretzmann B, Hicke L. Regulation of the RSP5 ubiquitin ligase by an intrinsic ubiquitin-binding site. J Biol Chem. 2009;284:12071-9 pubmed publisher
    ..The Nedd4 HECT domain N-lobe also contains ubiquitin-binding activity, suggesting that interactions between the N-lobe and ..
  48. He Y, Hryciw D, Carroll M, Myers S, Whitbread A, Kumar S, et al. The ubiquitin-protein ligase Nedd4-2 differentially interacts with and regulates members of the Tweety family of chloride ion channels. J Biol Chem. 2008;283:24000-10 pubmed publisher
    ..In addition to N-glycosylation, ubiquitination mediated by the HECT type E3 ubiquitin ligase Nedd4-2 is a post-translation modification important in regulating membrane proteins...
  49. Wang X, Shi Y, Wang J, Huang G, Jiang X. Crucial role of the C-terminus of PTEN in antagonizing NEDD4-1-mediated PTEN ubiquitination and degradation. Biochem J. 2008;414:221-9 pubmed publisher
    ..In the present study, we have investigated the mechanism and regulation of PTEN ubiquitination catalysed by NEDD4-1 (neural-precursor-cell-expressed, developmentally down-regulated 4-1), a ubiquitin ligase for PTEN we identified ..
  50. McDonald F, Western A, McNeil J, Thomas B, Olson D, Snyder P. Ubiquitin-protein ligase WWP2 binds to and downregulates the epithelial Na(+) channel. Am J Physiol Renal Physiol. 2002;283:F431-6 pubmed
    ..The channel is regulated by members of the Nedd4 family of ubiquitin-protein ligases, which bind to channel subunits and catalyze channel internalization and ..
  51. Kim H, Kim K, Lledias F, Kisselev A, Scaglione K, Skowyra D, et al. Certain pairs of ubiquitin-conjugating enzymes (E2s) and ubiquitin-protein ligases (E3s) synthesize nondegradable forked ubiquitin chains containing all possible isopeptide linkages. J Biol Chem. 2007;282:17375-86 pubmed
    ..However, the HECT domain E3s, E6AP and Nedd4, with the same E2, UbcH5, form homogeneous chains exclusively, either Lys(48) chains (E6AP) or Lys(63) chains (..
  52. Cristillo A, Nie L, Macri M, Bierer B. Cloning and characterization of N4WBP5A, an inducible, cyclosporine-sensitive, Nedd4-binding protein in human T lymphocytes. J Biol Chem. 2003;278:34587-97 pubmed
    We have cloned and characterized a human cDNA, designated N4WBP5A, that belongs to the family of Nedd4-binding proteins...
  53. Magnifico A, Ettenberg S, Yang C, Mariano J, Tiwari S, Fang S, et al. WW domain HECT E3s target Cbl RING finger E3s for proteasomal degradation. J Biol Chem. 2003;278:43169-77 pubmed
    ..Here we establish that two WW domain HECT E3s, Nedd4 and Itch, bind Cbl proteins and target them for proteasomal degradation...
  54. Woelk T, Oldrini B, Maspero E, Confalonieri S, Cavallaro E, Di Fiore P, et al. Molecular mechanisms of coupled monoubiquitination. Nat Cell Biol. 2006;8:1246-54 pubmed
    ..Furthermore, we demonstrate that the in vivo ubiquitination of members of the Nedd4 family of E3 ligases correlates with their ability to monoubiquitinate eps15...
  55. Mevissen T, Hospenthal M, Geurink P, Elliott P, Akutsu M, Arnaudo N, et al. OTU deubiquitinases reveal mechanisms of linkage specificity and enable ubiquitin chain restriction analysis. Cell. 2013;154:169-84 pubmed publisher
    ..We introduce Ub chain restriction analysis, in which OTU DUBs are used as restriction enzymes to reveal linkage type and the relative abundance of Ub chains on substrates. ..
  56. 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
    ..The Na(v)1.5 C-terminus contains a PY-motif (xPPxY) that is known to act as binding site for Nedd4/Nedd4-like ubiquitin-protein ligases...
  57. Wu K, Yan H, Fang L, Wang X, PFLEGER C, Jiang X, et al. Mono-ubiquitination drives nuclear export of the human DCN1-like protein hDCNL1. J Biol Chem. 2011;286:34060-70 pubmed publisher
    ..Using a classical chromatographic purification strategy, we identified Nedd4-1 as an E3 ligase that can catalyze mono-ubiquitination of hDCNL1 in a reconstituted ubiquitination system...
  58. Hatakeyama S, Jensen J, Weissman A. Subcellular localization and ubiquitin-conjugating enzyme (E2) interactions of mammalian HECT family ubiquitin protein ligases. J Biol Chem. 1997;272:15085-92 pubmed
    ..Furthermore, the presence of two E2 binding sites within Nedd-4 suggests models for ubiquitination involving multiple E2 enzymes associated with E3s. ..
  59. Winberg G, Matskova L, Chen F, Plant P, Rotin D, Gish G, et al. Latent membrane protein 2A of Epstein-Barr virus binds WW domain E3 protein-ubiquitin ligases that ubiquitinate B-cell tyrosine kinases. Mol Cell Biol. 2000;20:8526-35 pubmed
    ..Here we show that the PPPPY motifs of LMP2A bind multiple WW domains of E3 protein-ubiquitin ligases of the Nedd4 family, including AIP4 and KIAA0439, and demonstrate that AIP4 and KIAA0439 form physiological complexes with ..
  60. Schubert U, Ott D, Chertova E, Welker R, Tessmer U, Princiotta M, et al. Proteasome inhibition interferes with gag polyprotein processing, release, and maturation of HIV-1 and HIV-2. Proc Natl Acad Sci U S A. 2000;97:13057-62 pubmed
    ..These results indicate the requirement for an active proteasome/ubiquitin system in release and maturation of infectious HIV particles and provide a potential pharmaceutical strategy for interfering with retrovirus replication. ..
  61. Wang J, Peng Q, Lin Q, Childress C, Carey D, Yang W. Calcium activates Nedd4 E3 ubiquitin ligases by releasing the C2 domain-mediated auto-inhibition. J Biol Chem. 2010;285:12279-88 pubmed publisher
    b>Nedd4 E3 ligases are members of the HECT E3 ubiquitin ligase family and regulate ubiquitination-mediated protein degradation...
  62. Kanelis V, Rotin D, Forman Kay J. Solution structure of a Nedd4 WW domain-ENaC peptide complex. Nat Struct Biol. 2001;8:407-12 pubmed
    b>Nedd4 is a ubiquitin protein ligase composed of a C2 domain, three (or four) WW domains and a ubiquitin ligase Hect domain...
  63. Edwin F, Anderson K, Patel T. HECT domain-containing E3 ubiquitin ligase Nedd4 interacts with and ubiquitinates Sprouty2. J Biol Chem. 2010;285:255-64 pubmed publisher
    ..that Spry1 and Spry2, but not Spry3 or Spry4, associate with the HECT domain family E3 ubiquitin ligase, Nedd4. The Spry2/Nedd4 association involves the WW domains of Nedd4 and requires phosphorylation of the Mnk2 kinase ..
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