Nedd4

Summary

Gene Symbol: Nedd4
Description: neural precursor cell expressed, developmentally down-regulated 4
Alias: AA959633, AL023035, AU019897, E430025J12Rik, Nedd4-1, Nedd4a, mKIAA0093, E3 ubiquitin-protein ligase NEDD4, HECT-type E3 ubiquitin transferase NEDD4, NEDD-4, neural precursor cell expressed developmentally down-regulated protein 4, neural precursor cell expressed, developmentally down-regulated gene 4, neural precursor cell expressed, developmentally down-regulated gene 4a, neural precursor cell expressed, developmentally down-regulted gene 4
Species: mouse

Top Publications

  1. ncbi Function of WW domains as phosphoserine- or phosphothreonine-binding modules
    P J Lu
    Cancer Biology Program, Division of Hematology Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
    Science 283:1325-8. 1999
  2. ncbi N4WBP5, a potential target for ubiquitination by the Nedd4 family of proteins, is a novel Golgi-associated protein
    Kieran F Harvey
    Hanson Center for Cancer Research, Institute of Medical and Veterinary Science, Frome Road, Adelaide, South Australia 5000, Australia
    J Biol Chem 277:9307-17. 2002
  3. ncbi Serum- and glucocorticoid-regulated kinase 1 regulates ubiquitin ligase neural precursor cell-expressed, developmentally down-regulated protein 4-2 by inducing interaction with 14-3-3
    Vivek Bhalla
    Division of Nephrology, Department of Medicine, University of California San Francisco, San Francisco, CA 94143 0532, USA
    Mol Endocrinol 19:3073-84. 2005
  4. ncbi APOBEC3G ubiquitination by Nedd4-1 favors its packaging into HIV-1 particles
    Sylvie Dussart
    Inserm Unité 372, Universite de la Mediterranee, 163 Avenue de Luminy, BP178, 13276 Marseille Cedex 09, France
    J Mol Biol 345:547-58. 2005
  5. ncbi Identification of a set of genes with developmentally down-regulated expression in the mouse brain
    S Kumar
    Department of Viral Oncology, Cancer Institute, Tokyo, Japan
    Biochem Biophys Res Commun 185:1155-61. 1992
  6. pmc Nedd4 controls animal growth by regulating IGF-1 signaling
    Xiao R Cao
    Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
    Sci Signal 1:ra5. 2008
  7. pmc The ubiquitin ligase Nedd4-1 is dispensable for the regulation of PTEN stability and localization
    Fatemeh Fouladkou
    Hospital for Sick Children and Biochemistry Department, University of Toronto, MaRS TMDT, 101 College Street, Toronto, Ontario M5G 1L7, Canada
    Proc Natl Acad Sci U S A 105:8585-90. 2008
  8. pmc Abnormal development of the neuromuscular junction in Nedd4-deficient mice
    Yun Liu
    Department of Neuroscience, UT Southwestern Medical Center, 6000 Harry Hines Blvd, Dallas, TX 75390 9111, USA
    Dev Biol 330:153-66. 2009
  9. pmc Nedd4-2-mediated ubiquitination facilitates processing of surfactant protein-C
    Juliana J Conkright
    Cincinnati Children s Hospital Medical Center, Division of Pulmonary Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
    Am J Respir Cell Mol Biol 42:181-9. 2010
  10. pmc NEDD4-1 is a proto-oncogenic ubiquitin ligase for PTEN
    Xinjiang Wang
    Cell Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 522, New York, NY 10021, USA
    Cell 128:129-39. 2007

Research Grants

Scientific Experts

  • TERESA GUNN
  • Vivek Gautam
  • Qingqiu Huang
  • A Morrione
  • Hiroshi Kawabe
  • Sharad Kumar
  • Daniela Rotin
  • Daria Camera
  • Baoli Yang
  • Young Don Kwak
  • Fatemeh Fouladkou
  • Jean Sebastien Rougier
  • Natasha A Boase
  • Philip Poronnik
  • Sylvie Dussart
  • Xinjiang Wang
  • K F Harvey
  • Robert D'Cruz
  • David I Cook
  • Olivier Staub
  • Gary T Zeruth
  • Lin Yuan
  • C Xu
  • Francisco Bustos
  • David V Pow
  • Toshiaki Fukushima
  • Tao Zhou
  • Nancy N Fang
  • Marina Maria Bellet
  • Di Feng Fang
  • Samantha L Scudder
  • Pamela J Plant
  • Judy Correa
  • S Kumar
  • Alexander P Tuckow
  • Jianbo Sun
  • Fei Song
  • Joanna Fombonne
  • Hui Guo
  • Takeshi Terabayashi
  • Natasha Boase
  • Preena Nagpal
  • Svetlana V Kalinichenko
  • Jenny Lackovic
  • Anjali A Sarkar
  • Ruth Milkereit
  • Bin Wang
  • Huaxi Xu
  • Claude A Van Campenhout
  • Benjamin Oberfeld
  • Albert E Ayoub
  • Francesca Fang Liao
  • Paula M Oliver
  • Juliana J Conkright
  • Alexandre Simonin
  • Jacqueline F Aitken
  • Izumi Yunokuchi
  • Yun Liu
  • Nils Brose
  • Robert S Edinger
  • Chen Lu
  • Xuejun Jiang
  • Giada Monami
  • Xiao R Cao
  • Xiubin Liang
  • Hugues Abriel
  • Eileen M Sweezer
  • S Hatakeyama
  • Angeles Sanchez-Perez
  • Vivek Bhalla
  • Jeroen Bakkers
  • Etienne Decroly
  • Marc Douaisi
  • C N Jolliffe
  • Gilles Bessou
  • Marianne Courcoul
  • Robert Vigne
  • Joseph Murdaca
  • Vigo Heissmeyer
  • Andrew B Fotia
  • Kelly Gormley
  • Lesley A Pablo
  • Andrea Vecchione
  • Joanna Timmins
  • Harold A Coleman
  • Helena C Parkington
  • Trisha A Jenkins
  • James Bain
  • Jane Batt
  • Joshua Chackowicz

Detail Information

Publications77

  1. ncbi Function of WW domains as phosphoserine- or phosphothreonine-binding modules
    P J Lu
    Cancer Biology Program, Division of Hematology Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
    Science 283:1325-8. 1999
    ..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. ncbi N4WBP5, a potential target for ubiquitination by the Nedd4 family of proteins, is a novel Golgi-associated protein
    Kieran F Harvey
    Hanson Center for Cancer Research, Institute of Medical and Veterinary Science, Frome Road, Adelaide, South Australia 5000, Australia
    J Biol Chem 277:9307-17. 2002
    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...
  3. ncbi Serum- and glucocorticoid-regulated kinase 1 regulates ubiquitin ligase neural precursor cell-expressed, developmentally down-regulated protein 4-2 by inducing interaction with 14-3-3
    Vivek Bhalla
    Division of Nephrology, Department of Medicine, University of California San Francisco, San Francisco, CA 94143 0532, USA
    Mol Endocrinol 19:3073-84. 2005
    ..Recent evidence has established that SGK1 phosphorylates and inhibits Nedd4-2 (neural precursor cell-expressed, developmentally down-regulated protein 4-2), a ubiquitin ligase that decreases ..
  4. ncbi APOBEC3G ubiquitination by Nedd4-1 favors its packaging into HIV-1 particles
    Sylvie Dussart
    Inserm Unité 372, Universite de la Mediterranee, 163 Avenue de Luminy, BP178, 13276 Marseille Cedex 09, France
    J Mol Biol 345:547-58. 2005
    ..Here, we demonstrate that Nedd4-1, an HECT E3 ubiquitin ligase, interacts with APOBEC3G, through its WW2 and WW3 domains...
  5. ncbi Identification of a set of genes with developmentally down-regulated expression in the mouse brain
    S Kumar
    Department of Viral Oncology, Cancer Institute, Tokyo, Japan
    Biochem Biophys Res Commun 185:1155-61. 1992
    ..Their patterns of expression indicate that these genes may play important roles during the embryonic development and differentiation of central nervous system...
  6. pmc Nedd4 controls animal growth by regulating IGF-1 signaling
    Xiao R Cao
    Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
    Sci Signal 1:ra5. 2008
    The ubiquitin ligase Nedd4 has been proposed to regulate a number of signaling pathways, but its physiological role in mammals has not been characterized...
  7. pmc The ubiquitin ligase Nedd4-1 is dispensable for the regulation of PTEN stability and localization
    Fatemeh Fouladkou
    Hospital for Sick Children and Biochemistry Department, University of Toronto, MaRS TMDT, 101 College Street, Toronto, Ontario M5G 1L7, Canada
    Proc Natl Acad Sci U S A 105:8585-90. 2008
    PTEN is a tumor suppressor frequently mutated in cancer. Recent reports implicated Nedd4-1 as the E3 ubiquitin ligase for PTEN that regulates its stability and nuclear localization...
  8. pmc Abnormal development of the neuromuscular junction in Nedd4-deficient mice
    Yun Liu
    Department of Neuroscience, UT Southwestern Medical Center, 6000 Harry Hines Blvd, Dallas, TX 75390 9111, USA
    Dev Biol 330:153-66. 2009
    b>Nedd4 (neural precursor cell expressed developmentally down-regulated gene 4) is an E3 ubiquitin ligase highly conserved from yeast to humans...
  9. pmc Nedd4-2-mediated ubiquitination facilitates processing of surfactant protein-C
    Juliana J Conkright
    Cincinnati Children s Hospital Medical Center, Division of Pulmonary Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
    Am J Respir Cell Mol Biol 42:181-9. 2010
    ..Purified recombinant glutathione S-transferase-SP-C propeptide (residues 1-35) bound recombinant Nedd4-2 strongly, and Nedd4 weakly; the S(12)PPDYS(17)mutation abrogated binding of SP-C to Nedd4-2...
  10. pmc NEDD4-1 is a proto-oncogenic ubiquitin ligase for PTEN
    Xinjiang Wang
    Cell Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 522, New York, NY 10021, USA
    Cell 128:129-39. 2007
    ..regulated by ubiquitin-mediated proteasomal degradation, and purified its ubiquitin ligase as HECT-domain protein NEDD4-1. In cells NEDD4-1 negatively regulates PTEN stability by catalyzing PTEN polyubiquitination...
  11. pmc The ubiquitin ligase Nedd4-1 is required for heart development and is a suppressor of thrombospondin-1
    Fatemeh Fouladkou
    Program in Cell Biology and the Mouse Imaging Centre, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada
    J Biol Chem 285:6770-80. 2010
    b>Nedd4 (Nedd4-1) is a Hect domain E3 ubiquitin ligase that also contains a C2 domain and three WW domains. Despite numerous in vitro studies, its biological function in vivo is not well understood...
  12. ncbi Molecular determinants of voltage-gated sodium channel regulation by the Nedd4/Nedd4-like proteins
    Jean Sebastien Rougier
    Department of Pharmacology and Toxicology, Service of Cardiology, University of Lausanne, Rue du Bugnon 27, CH 1005 Lausanne, Switzerland
    Am J Physiol Cell Physiol 288:C692-701. 2005
    ..COOH-terminal sequence, PPSYDSV, is a PY motif known to bind to WW domains of E3 protein-ubiquitin ligases of the Nedd4 family. We recently reported that cardiac Na(v)1.5 is regulated by Nedd4-2...
  13. pmc Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite development
    Hiroshi Kawabe
    Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Gottingen, Germany
    Neuron 65:358-72. 2010
    b>Nedd4-1 is a "neuronal precursor cell expressed and developmentally downregulated protein" and among the most abundant E3 ubiquitin ligases in mammalian neurons...
  14. ncbi cDNA cloning, expression analysis, and mapping of the mouse Nedd4 gene
    S Kumar
    The Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Rundle Mall, Adelaide, South Australia, 5000, Australia
    Genomics 40:435-43. 1997
    The Nedd4 gene was initially identified by a subtraction cloning approach as a highly expressed transcript in the mouse embryonic brain...
  15. ncbi Nedd4-like proteins: an emerging family of ubiquitin-protein ligases implicated in diverse cellular functions
    K F Harvey
    Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Frome Road, Adelaide, SA 5000, Australia
    Trends Cell Biol 9:166-9. 1999
    The members of an emerging family of proteins similar to Nedd4 have a unique modular structure consisting of a Ca2+/lipid-binding domain, multiple protein-protein interaction modules and a ubiquitin-protein ligase domain...
  16. ncbi A novel mouse Nedd4 protein suppresses the activity of the epithelial Na+ channel
    E Kamynina
    Institute of Pharmacology and Toxicology, University of Lausanne, 1005 Lausanne, Switzerland
    FASEB J 15:204-214. 2001
    ..mutations alter or delete PY motifs involved in protein-protein interactions with a ubiquitin-protein ligase, Nedd4. Here we show that Na+ transporting cells, derived from mouse cortical collecting duct, express two Nedd4 proteins ..
  17. doi Learning, memory and long-term potentiation are altered in Nedd4 heterozygous mice
    Daria Camera
    Health Innovations Research Institute, School of Medical Science, RMIT University, P O Box 71, Bundoora, VIC 3083, Australia
    Behav Brain Res 303:176-81. 2016
    ..AMPA receptor trafficking is a key determinant of LTP and recently ubiquitination by Nedd4 has been shown to play an important role via direct action on the GluA1 subunit, although the physiological ..
  18. pmc Rsp5/Nedd4 is the main ubiquitin ligase that targets cytosolic misfolded proteins following heat stress
    Nancy N Fang
    Department of Biochemistry and Molecular Biology, Centre for High Throughput Biology, University of British Columbia, 2125 East Mall Vancouver, British Columbia V6T1Z4, Canada
    Nat Cell Biol 16:1227-37. 2014
    ..We found that Rsp5 and its mammalian homologue Nedd4 are important E3 ligases responsible for the increased ubiquitylation induced by heat stress...
  19. doi PDLIM7 is a novel target of the ubiquitin ligase Nedd4-1 in skeletal muscle
    Robert D'Cruz
    Keenan Center for Biomedical Research, St Michaels Hospital, Toronto, Ontario, Canada, M5B 1W8
    Biochem J 473:267-76. 2016
    ..system (UPS) is the predominant proteolytic machinery responsible for atrophy of skeletal muscle, and Nedd4-1 (neural precursor cell-expressed developmentally down-regulated 4-1) is one of a series of E3 ubiquitin ligases ..
  20. pmc NEDD4 Regulates PAX7 Levels Promoting Activation of the Differentiation Program in Skeletal Muscle Precursors
    Francisco Bustos
    Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago, Chile
    Stem Cells 33:3138-51. 2015
    ..Here we show that Pax7 levels are directly regulated by the ubiquitin-ligase Nedd4. Our results indicate that Nedd4 is expressed in quiescent and activated satellite cells, that Nedd4 and Pax7 ..
  21. doi Deubiquitylase OTUD3 regulates PTEN stability and suppresses tumorigenesis
    Lin Yuan
    State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Collaborative Innovation Center for Cancer Medicine, Beijing 100850, China
    Nat Cell Biol 17:1169-81. 2015
    ..These findings demonstrate that OTUD3 is an essential regulator of PTEN and that the OTUD3-PTEN signalling axis plays a critical role in tumour suppression. ..
  22. pmc HECT E3 Ubiquitin Ligase Itch Functions as a Novel Negative Regulator of Gli-Similar 3 (Glis3) Transcriptional Activity
    Gary T Zeruth
    Cell Biology Section, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, United States of America
    PLoS ONE 10:e0131303. 2015
    ..These include the WW-domain-containing HECT E3 ubiquitin ligases, Itch, Smurf2, and Nedd4. The interaction between Glis3 and the HECT E3 ubiquitin ligases was verified by co-immunoprecipitation assays and ..
  23. doi Nedd4-induced monoubiquitination of IRS-2 enhances IGF signalling and mitogenic activity
    Toshiaki Fukushima
    1 Department of Animal Sciences and Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1 1 1 Yayoi, Bunkyo ku, Tokyo 113 8657, Japan 2 Department of Medical Science, Graduate School of Medicine, Hiroshima University, 1 2 3 Kasumi, Minami Ku, Hiroshima City, Hiroshima 734 8553, Japan
    Nat Commun 6:6780. 2015
    ..Here we identify Nedd4 as an IRS-2 ubiquitin ligase...
  24. pmc Functional interaction of phosphatase and tensin homologue (PTEN) with the E3 ligase NEDD4-1 during neuronal response to zinc
    Young Don Kwak
    Neurodegenerative Disease Program, Burnham Institute for Medical Research, La Jolla, California 92037, USA
    J Biol Chem 285:9847-57. 2010
    ..b>NEDD4-1-mediated PTEN ubiquitination and subsequent degradation via the ubiquitin proteosomal system have recently been ..
  25. pmc Synaptic strength is bidirectionally controlled by opposing activity-dependent regulation of Nedd4-1 and USP8
    Samantha L Scudder
    University of California San Diego, Section of Neurobiology, Division of Biological Sciences, La Jolla, California 92093
    J Neurosci 34:16637-49. 2014
    ..Previous work has demonstrated that AMPARs undergo activity-dependent ubiquitination by the E3 ubiquitin ligase Nedd4-1, which promotes their internalization and degradation in lysosomes...
  26. pmc Nedd4-1 and beta-arrestin-1 are key regulators of Na+/H+ exchanger 1 ubiquitylation, endocytosis, and function
    Alexandre Simonin
    Department of Nephrology and Hypertension, University Hospital of Bern, Freiburgstrasse 15, 3010 Bern, Switzerland
    J Biol Chem 285:38293-303. 2010
    ..This process requires the adapter protein β-arrestin-1 that interacts with both the E3 ubiquitin ligase Nedd4-1 and the NHE1 C terminus...
  27. pmc Neuronal precursor cell-expressed developmentally down-regulated 4-1 (NEDD4-1) controls the sorting of newly synthesized Ca(V)1.2 calcium channels
    Jean Sebastien Rougier
    Department of Neurosciences, Physiology, and Pharmacology, University College London, London WC1E 6BT, United Kingdom
    J Biol Chem 286:8829-38. 2011
    Neuronal precursor cell-expressed developmentally down-regulated 4 (Nedd4) proteins are ubiquitin ligases, which attach ubiquitin moieties to their target proteins, a post-translational modification that is most commonly associated with ..
  28. pmc Respiratory distress and perinatal lethality in Nedd4-2-deficient mice
    Natasha A Boase
    Department of Haematology, Centre for Cancer Biology, SA Pathology, PO Box 14, Rundle Mall, Adelaide, South Australia 5000, Australia
    Nat Commun 2:287. 2011
    ..In vitro studies show that the ubiquitin ligase Nedd4-2 ubiquitinates ENaC to regulate its cell surface expression...
  29. pmc E3 ubiquitin ligase Cbl-b regulates Pten via Nedd4 in T cells independently of its ubiquitin ligase activity
    Hui Guo
    Section of Nephrology, Department of Medicine, The University of Chicago, 5841 S Maryland Avenue, Chicago, IL 60637, USA
    Cell Rep 1:472-82. 2012
    ..Suppression of Pten inactivation in T cells by Cbl-b is achieved by impeding the association of Pten with Nedd4, which targets Pten K13 for K63-linked polyubiquitination...
  30. pmc Upregulation of the E3 ligase NEDD4-1 by oxidative stress degrades IGF-1 receptor protein in neurodegeneration
    Young Don Kwak
    Department of Pharmacology, University of Tennessee Health Science Center, College of Medicine, Memphis, Tennessee 38163, USA
    J Neurosci 32:10971-81. 2012
    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...
  31. pmc E3-ubiquitin ligase Nedd4 determines the fate of AID-associated RNA polymerase II in B cells
    Jianbo Sun
    Department of Microbiology and Immunology, Columbia University, New York, New York 10032, USA
    Genes Dev 27:1821-33. 2013
    ..Here we report that E3-ubiquitin ligase Nedd4 destabilizes AID-associated RNA polII by a ubiquitination event, leading to generation of 3' end free RNA exosome ..
  32. doi Subtle gait abnormalities in Nedd4 heterozygous mice
    Daria Camera
    Health Innovations Research Institute, School of Medical Science, RMIT University, PO Box 71, Bundoora, VIC 3083, Australia
    Behav Brain Res 260:15-24. 2014
    b>Nedd4 is a widely expressed ubiquitin ligase that is necessary for normal neuronal development and function...
  33. doi Regulation of Mdm2 protein stability and the p53 response by NEDD4-1 E3 ligase
    C Xu
    Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY, USA
    Oncogene 34:281-9. 2015
    ..Here we report biochemical identification of NEDD4-1 as an E3 ligase for Mdm2 that contributes to the regulation of Mdm2 protein stability in cells...
  34. pmc NEDD4 controls the expression of GUCD1, a protein upregulated in proliferating liver cells
    Marina Maria Bellet
    Department of Experimental Medicine University of Perugia Perugia, Italy
    Cell Cycle 13:1902-11. 2014
    ..assay, aimed at identifying any relevant interaction partners of GUCD1, revealed direct interactions with NEDD4-1 (E3 ubiquitin protein ligase neural precursor cell expressed, developmentally downregulated gene 4), resulting ..
  35. doi NEDD4 ubiquitinates TRAF3 to promote CD40-mediated AKT activation
    Di Feng Fang
    1 State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Institute of Basic Medical Sciences, Beijing 100850, China 2
    Nat Commun 5:4513. 2014
    ..Here we report that the neural precursor cell expressed developmentally downregulated protein 4 (NEDD4), homologous to E6-AP Carboxyl Terminus family E3 ubiquitin ligase, is a novel component of the CD40 signalling ..
  36. ncbi The Vif protein of human immunodeficiency virus type 1 is posttranslationally modified by ubiquitin
    Sylvie Dussart
    INSERM Unit 372, Universite de la Mediterranee, 163 Avenue de Luminy, BP178, 13276 Marseille Cedex 09, France
    Biochem Biophys Res Commun 315:66-72. 2004
    ..Vif is mainly mono-ubiquitinated, a modification known to address the Gag precursor to the virus budding site...
  37. pmc The Thoc1 encoded ribonucleoprotein is a substrate for the NEDD4-1 E3 ubiquitin protein ligase
    Fei Song
    Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, New York, United States of America
    PLoS ONE 8:e57995. 2013
    ..we demonstrate that the essential THO protein component encoded by the Thoc1 gene is poly-ubiquitinated by the NEDD4-1 E3 ubiquitin ligase. Poly-ubiquitinated pThoc1 is degraded by the proteasome...
  38. pmc Patched dependence receptor triggers apoptosis through ubiquitination of caspase-9
    Joanna Fombonne
    Apoptosis, Cancer and Development Laboratory Equipe labellisée La Ligue, LabEx DEVweCAN, Centre de Cancérologie de Lyon, Institut, Universite de Lyon, 69008 Lyon, France
    Proc Natl Acad Sci U S A 109:10510-5. 2012
    ..We show here that this caspase-activating complex also includes the E3 ubiquitin ligase NEDD4. We demonstrate that Ptc-mediated apoptosis and Ptc-induced caspase-9 activation require NEDD4...
  39. ncbi U box proteins as a new family of ubiquitin-protein ligases
    S Hatakeyama
    Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka 812 8582, Japan
    J Biol Chem 276:33111-20. 2001
    ..These data suggest that U box proteins constitute a third family of E3 enzymes and that E4 activity may reflect a specialized type of E3 activity...
  40. pmc Identification of ubiquitin-modified lysine residues and novel phosphorylation sites on eukaryotic initiation factor 2B epsilon
    Alexander P Tuckow
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Biochem Biophys Res Commun 436:41-6. 2013
    ..Moreover, peptides corresponding to the amino acid sequence of the E3 ligase NEDD4 were also detected in the LC-MS/MS analysis, and an interaction between endogenous eIF2Bε with NEDD4 was ..
  41. pmc An obligatory heterodimer of 14-3-3beta and 14-3-3epsilon is required for aldosterone regulation of the epithelial sodium channel
    Xiubin Liang
    Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    J Biol Chem 283:27418-25. 2008
    Increased distal nephron sodium absorption in response to aldosterone involves Nedd4-2 phosphorylation, which blocks its ability to ubiquitylate ENaC and increases apical membrane channel density by reducing its endocytosis...
  42. pmc MGRN1-dependent pigment-type switching requires its ubiquitination activity but not its interaction with TSG101 or NEDD4
    Teresa M Gunn
    McLaughlin Research Institute, Great Falls, MT, USA Department of Biomedical Sciences, Cornell University, Ithaca, NY, USA
    Pigment Cell Melanoma Res 26:263-8. 2013
    ..Here, we show that MGRN1 also interacts with but does not ubiquitinate NEDD4, a HECT-domain ubiquitin ligase involved in endosomal trafficking...
  43. pmc The ubiquitin ligase Nedd4-1 participates in denervation-induced skeletal muscle atrophy in mice
    Preena Nagpal
    Keenan Research Centre of the LiKaShing Knowledge Institute, St Michaels Hospital, Toronto, Ontario, Canada
    PLoS ONE 7:e46427. 2012
    ..Our previous work suggested that the ubiquitin-protein ligase Nedd4-1 is a potential mediator of skeletal muscle atrophy associated with inactivity (denervation, unloading and ..
  44. pmc Phosphorylation of Kif26b promotes its polyubiquitination and subsequent proteasomal degradation during kidney development
    Takeshi Terabayashi
    Department of Kidney Development, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan
    PLoS ONE 7:e39714. 2012
    ..interacts with an E3 ubiquitin ligase, neural precursor cell expressed developmentally down-regulated protein 4 (Nedd4) in developing kidney...
  45. pmc Nedd4 is a specific E3 ubiquitin ligase for the NMDA receptor subunit GluN2D
    Vivek Gautam
    Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985800 Nebraska Medical Center, Omaha, NE 68198 5800, USA
    Neuropharmacology 74:96-107. 2013
    ..fragments used as bait, only the construct containing amino acids 983-1097 associated with an E3 ubiquitin ligase, Nedd4. A direct interaction between GluN2D and Nedd4 was confirmed both in vivo and in vitro...
  46. pmc Identification of Nedd4 E3 ubiquitin ligase as a binding partner and regulator of MAK-V protein kinase
    Svetlana V Kalinichenko
    Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia
    PLoS ONE 7:e39505. 2012
    ..However molecular mechanisms of MAK-V action and regulation of its activity remain largely unknown. We identified Nedd4 as an interaction partner for MAK-V protein kinase...
  47. pmc Hectd1 regulates intracellular localization and secretion of Hsp90 to control cellular behavior of the cranial mesenchyme
    Anjali A Sarkar
    Center for Neuroscience Research, Children s Research Institute, Children s National Medical Center, Washington, DC 20010, USA
    J Cell Biol 196:789-800. 2012
    ....
  48. doi Differential regulation of Nedd4 ubiquitin ligases and their adaptor protein Ndfip1 in a rat model of ischemic stroke
    Jenny Lackovic
    Brain Development and Regeneration Laboratory, Florey Neuroscience Institutes, The University of Melbourne, Parkville, Australia
    Exp Neurol 235:326-35. 2012
    ..Here, we demonstrate endogenous induction of HECT-type E3 ligases of the Nedd4 family and their adaptor Nedd4-family interacting protein 1 (Ndfip1) following transient focal cerebral ischemia ..
  49. pmc A role for the ubiquitin ligase Nedd4 in membrane sorting of LAPTM4 proteins
    Ruth Milkereit
    Program in Cell Biology, The Hospital for Sick Children, Biochemistry Department, University of Toronto, Toronto, Ontario, Canada
    PLoS ONE 6:e27478. 2011
    ..While we had demonstrated earlier the requirement of the E3 ubiquitin ligase Nedd4 for LAPTM5 sorting to lysosomes, the regulation of sorting of LAPTM4 proteins is less clear.
  50. pmc Tetracycline treatment retards the onset and slows the progression of diabetes in human amylin/islet amyloid polypeptide transgenic mice
    Jacqueline F Aitken
    School of Biological Sciences, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
    Diabetes 59:161-71. 2010
    ..Here, we used tetracycline, which modifies hA/hIAPP oligomerization, to probe mechanisms whereby hA/hIAPP causes diabetes in hemizygous hA/hIAPP-transgenic mice...
  51. ncbi Alternative splicing determines the domain structure of WWP1, a Nedd4 family protein
    Marzena Flasza
    School of Biological Sciences, University of Manchester, 2 205 Stopford Building, Oxford Road, Manchester M13 9PT, United Kingdom
    Biochem Biophys Res Commun 290:431-7. 2002
    ..Here we show that a human Nedd4 family gene, WWP1, is localized on 8q21 and generates at least six isoforms through alternative splicing...
  52. ncbi Isolation of differentially expressed genes from wild-type and Twist mutant mouse limb buds
    David A F Loebel
    Embryology Unit, Children s Medical Research Institute, Westmead, New South Wales, Australia
    Genesis 33:103-13. 2002
    ....
  53. ncbi Identification of developmentally expressed proteins that functionally interact with Nedd4 ubiquitin ligase
    Rodolfo Murillas
    Experimental Immunology Branch, NCI, National Institutes of Health, Bethesda, Maryland 20892 1360, USA
    J Biol Chem 277:2897-907. 2002
    b>Nedd4 is a HECT domain-containing ubiquitin ligase that mediates ubiquitylation and proteasome degradation of target proteins...
  54. pmc Identification of multiple proteins expressed in murine embryos as binding partners for the WW domains of the ubiquitin-protein ligase Nedd4
    C N Jolliffe
    Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, P O Box 14, Rundle Mall, Adelaide, SA 5000, Australia
    Biochem J 351:557-65. 2000
    b>Nedd4 is a member of a growing family of ubiquitin-protein ligases which consist of a lipid-binding domain, two to four WW domains and a C-terminal ubiquitin-protein ligase domain...
  55. ncbi Analysis of Nedd4 expression during skeletal development in the mouse limb
    A D Weston
    Department of Physiology, Faculty of Medicine and Dentistry, The University of Western Ontario, London, Canada
    Mech Dev 94:247-50. 2000
    b>Nedd4, a ubiquitin-protein ligase, was originally identified as being down-regulated during development of the mouse brain (Nedd denotes neural precursor cell expressed developmentally down-regulated) (Kumar, S., Tomooka, Y., Noda, M...
  56. ncbi mGrb10 interacts with Nedd4
    A Morrione
    Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    J Biol Chem 274:24094-9. 1999
    ..We have isolated a mouse cDNA clone containing the C2 domain of mouse Nedd4, a ubiquitin protein ligase (E3) that also contains a hect (homologous to the E6-AP carboxyl-terminus) domain and ..
  57. ncbi All three WW domains of murine Nedd4 are involved in the regulation of epithelial sodium channels by intracellular Na+
    K F Harvey
    Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Frome Road, Adelaide, SA 5000, Australia
    J Biol Chem 274:12525-30. 1999
    ..contains a PPxY motif which is necessary 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 PY motif of either ..
  58. ncbi The WW domain of neural protein FE65 interacts with proline-rich motifs in Mena, the mammalian homolog of Drosophila enabled
    K S Ermekova
    Department of Biochemistry, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Biol Chem 272:32869-77. 1997
    ....
  59. ncbi Interaction of WW domains with hematopoietic transcription factor p45/NF-E2 and RNA polymerase II
    N R Gavva
    Section of Molecular and Cellular Biology, University of California, Davis, California 95616, USA
    J Biol Chem 272:24105-8. 1997
    ..We discuss the data in terms of possible new pathways through which the processes of transcriptional regulation by NF-E2 could be regulated in erythroid and megakaryote cells...
  60. ncbi Subcellular localization and ubiquitin-conjugating enzyme (E2) interactions of mammalian HECT family ubiquitin protein ligases
    S Hatakeyama
    Laboratory of Immune Cell Biology, Division of Basic Sciences, NCI, National Institutes of Health, Bethesda, Maryland 20892 1152, USA
    J Biol Chem 272:15085-92. 1997
    ..Furthermore, the presence of two E2 binding sites within Nedd-4 suggests models for ubiquitination involving multiple E2 enzymes associated with E3s...
  61. pmc WW domains of Nedd4 bind to the proline-rich PY motifs in the epithelial Na+ channel deleted in Liddle's syndrome
    O Staub
    The Hospital for Sick Children, Division of Respiratory Research, Toronto, Ontario, Canada
    EMBO J 15:2371-80. 1996
    ..Using a yeast two-hybrid screen, we have now identified the rat homologue of Nedd4 (rNedd4) as the binding partner for the P2 regions of beta and gammarENaC...
  62. pmc Regulation of the epithelial sodium channel by accessory proteins
    Kelly Gormley
    Division of Neurosciences, St George s Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK
    Biochem J 371:1-14. 2003
    ..Several proteins acting in concert are an intrinsic part of this process but Nedd4 (neural precursor cell expressed developmentally down-regulated 4) is of central importance...
  63. ncbi Ebola virus matrix protein VP40 interaction with human cellular factors Tsg101 and Nedd4
    Joanna Timmins
    European Molecular Biology Laboratory, 6 rue Jules Horowitz, 38042 Grenoble, France
    J Mol Biol 326:493-502. 2003
    ..Here, we report that Ebola VP40 can interact with cellular factors human Nedd4 and Tsg101 in vitro...
  64. pmc Dlg3 trafficking and apical tight junction formation is regulated by nedd4 and nedd4-2 e3 ubiquitin ligases
    Claude A Van Campenhout
    Institute of Stem Cell Research, Helmholtz Zentrum Munchen, 85764 Neuherberg, Germany
    Dev Cell 21:479-91. 2011
    ..Remarkably, of the four Dlg family members, Dlg3 exerts a distinct function by recruiting the ubiquitin ligases Nedd4 and Nedd4-2 through its PPxY motifs...
  65. pmc Transcriptional programs in transient embryonic zones of the cerebral cortex defined by high-resolution mRNA sequencing
    Albert E Ayoub
    Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06520, USA
    Proc Natl Acad Sci U S A 108:14950-5. 2011
    ..Additionally, we found intergenic transcriptionally active regions that possibly encode unique zone-specific transcripts. Finally, we present a high-resolution transcriptome map of transient zones in the embryonic mouse forebrain...
  66. pmc The Grb10/Nedd4 complex regulates ligand-induced ubiquitination and stability of the insulin-like growth factor I receptor
    Andrea Vecchione
    Department of Urology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    Mol Cell Biol 23:3363-72. 2003
    ..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...
  67. doi Ubiquitin-specific protease 2-45 (Usp2-45) binds to epithelial Na+ channel (ENaC)-ubiquitylating enzyme Nedd4-2
    Benjamin Oberfeld
    Institute of Physiology, University of Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
    Am J Physiol Renal Physiol 301:F189-96. 2011
    ..by ubiquitylation is controlled by the activity of two counteracting enzymes, the E3 ubiquitin-protein ligase Nedd4-2 (mouse ortholog of human Nedd4L) and the ubiquitin-specific protease Usp2-45...
  68. ncbi Calcineurin imposes T cell unresponsiveness through targeted proteolysis of signaling proteins
    Vigo Heissmeyer
    Center for Blood Research and Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Nat Immunol 5:255-65. 2004
    ..Subsequent stimulation or homotypic cell adhesion promoted membrane translocation of Itch and the related protein Nedd4, resulting in degradation of two key signaling proteins, PKC-theta and PLC-gamma1...
  69. pmc Structural basis for the interaction between the growth factor-binding protein GRB10 and the E3 ubiquitin ligase NEDD4
    Qingqiu Huang
    MacCHESS, Cornell University, Ithaca, New York 14853, USA
    J Biol Chem 285:42130-9. 2010
    ..It has been shown that GRB10 can interact with the C2 domain of the E3 ubiquitin ligase NEDD4 through its Src homology 2 (SH2) domain...
  70. ncbi Grb10 prevents Nedd4-mediated vascular endothelial growth factor receptor-2 degradation
    Joseph Murdaca
    INSERM U145, Institut Federatif de Recherche 50, Faculte de Medecine, 06107 Nice Cedex 2, France
    J Biol Chem 279:26754-61. 2004
    ..In the present manuscript, we demonstrate that Grb10 stimulates VEGF-R2 expression by inhibiting the Nedd4-mediated VEGF-R2 degradation...
  71. ncbi Regulation of neuronal voltage-gated sodium channels by the ubiquitin-protein ligases Nedd4 and Nedd4-2
    Andrew B Fotia
    Hanson Institute, Institute of Medical and Veterinary Science, Frome Road, Adelaide, South Australia 5000, Australia
    J Biol Chem 279:28930-5. 2004
    b>Nedd4 and Nedd4-2 are ubiquitin-protein ligases known to regulate a number of membrane proteins including receptors and ion transporters...
  72. ncbi Destabilization of DeltaNp63alpha by Nedd4-mediated ubiquitination and Ubc9-mediated sumoylation, and its implications on dorsoventral patterning of the zebrafish embryo
    Jeroen Bakkers
    Max Planck Institute for Immunobiology, Stuebeweg 51, D 79108 Freiburg, Germany
    Cell Cycle 4:790-800. 2005
    ..we isolated two DeltaNp63alpha-modifying enzymes, the SUMO-conjugating enzyme Ubc9 and the ubiquitin ligase Nedd4. The proteins bind to distinct sites in the C-terminal region of DeltaNp63alpha, which are absent in the shorter ..
  73. doi Prolyl isomerase Pin1 shares functional similarity with phosphorylated CTD interacting factor PCIF1 in vertebrate cells
    Izumi Yunokuchi
    Department of Molecular and Cellular Biology, Cancer Research Institute, Kanazawa University, Kanazawa 920 0934, Japan
    Genes Cells 14:1105-18. 2009
    ..These results suggest that Pin1 may have overlapping cellular function with PCIF1 in vertebrate cells...
  74. ncbi GRK2 interacts with and phosphorylates Nedd4 and Nedd4-2
    Angeles Sanchez-Perez
    Bosch Institute, Department of Pathology, University of Sydney, Sydney, NSW 2006, Australia
    Biochem Biophys Res Commun 359:611-5. 2007
    ..They are inhibited by ubiquitin protein ligases, such as Nedd4 and Nedd4-2, which bind to proline-rich motifs (PY motifs) present in the C-termini of ENaC subunits...
  75. doi Grb10/Nedd4-mediated multiubiquitination of the insulin-like growth factor receptor regulates receptor internalization
    Giada Monami
    Department of Urology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    J Cell Physiol 216:426-37. 2008
    ..We have shown that Grb10 binds the E3 ubiquitin ligase Nedd4 and promotes IGF-I-stimulated ubiquitination, internalization, and degradation of the IGF-IR, thereby giving rise ..
  76. pmc Functional regulation of the epithelial Na+ channel by IkappaB kinase-beta occurs via phosphorylation of the ubiquitin ligase Nedd4-2
    Robert S Edinger
    Renal Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    J Biol Chem 284:150-7. 2009
    ..stimulation of ENaC activity occurs through enhanced channel surface expression and the ubiquitin-protein ligase Nedd4-2 has emerged as a central locus for ENaC regulation at the plasma membrane, we tested the role of Nedd4-2 in this ..
  77. pmc Nedd4 augments the adaptive immune response by promoting ubiquitin-mediated degradation of Cbl-b in activated T cells
    Baoli Yang
    Department of Obstetrics and Gynecology, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA
    Nat Immunol 9:1356-63. 2008
    b>Nedd4 and Itch are E3 ubiquitin ligases that ubiquitinate similar targets in vitro and thus are thought to function similarly. T cells lacking Itch show spontaneous activation and T helper type 2 polarization...

Research Grants1

  1. Functional analysis of Attractin-Mahogunin signaling
    TERESA GUNN; Fiscal Year: 2007
    ..As Mgn mutants display some phenotypes not observed in Atrn mutants, Lrn may compensate for loss of Atrn in some tissues and loss of both Lrn and Atrn may recapitulate the full Mgn phenotype. [unreadable] [unreadable]..