Parkin

Summary

Gene Symbol: Parkin
Description: parkin RBR E3 ubiquitin protein ligase
Alias: AR-JP, LPRS2, PDJ, PRKN, E3 ubiquitin-protein ligase parkin, Parkinson disease (autosomal recessive, juvenile) 2, parkin, parkinson juvenile disease protein 2, parkinson protein 2, E3 ubiquitin protein ligase (parkin)
Species: human

Top Publications

  1. pmc Parkin is recruited selectively to impaired mitochondria and promotes their autophagy
    Derek Narendra
    Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 183:795-803. 2008
  2. ncbi Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism
    T Kitada
    Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan
    Nature 392:605-8. 1998
  3. doi PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1
    Sven Geisler
    Laboratory of Functional Neurogenetics, Otfried Muller Strasse 27, 72076 Tubingen, Germany
    Nat Cell Biol 12:119-31. 2010
  4. pmc PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy
    Noriyuki Matsuda
    Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Setagaya Ku, Tokyo 156 8506, Japan
    J Cell Biol 189:211-21. 2010
  5. pmc Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin
    Atsushi Tanaka
    Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 191:1367-80. 2010
  6. pmc Autoregulation of Parkin activity through its ubiquitin-like domain
    Viduth K Chaugule
    Protein Structure and Function Laboratory, Cancer Research UK, London Research Institute, London, UK
    EMBO J 30:2853-67. 2011
  7. ncbi Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase
    H Shimura
    Department of Neurology, Juntendo University School of Medicine, Bunkyo ku, Tokyo, Japan
    Nat Genet 25:302-5. 2000
  8. pmc Mitofusin 1 and mitofusin 2 are ubiquitinated in a PINK1/parkin-dependent manner upon induction of mitophagy
    Matthew E Gegg
    Department of Clinical Neurosciences, Institute of Neurology, University College London, London, UK
    Hum Mol Genet 19:4861-70. 2010
  9. pmc Broad activation of the ubiquitin-proteasome system by Parkin is critical for mitophagy
    Nickie C Chan
    Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    Hum Mol Genet 20:1726-37. 2011
  10. ncbi Loss-of-function of human PINK1 results in mitochondrial pathology and can be rescued by parkin
    Nicole Exner
    Center for Integrated Protein Science Munich and Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University, 80336 Munich, Germany
    J Neurosci 27:12413-8. 2007

Detail Information

Publications246 found, 100 shown here

  1. pmc Parkin is recruited selectively to impaired mitochondria and promotes their autophagy
    Derek Narendra
    Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 183:795-803. 2008
    Loss-of-function mutations in Park2, the gene coding for the ubiquitin ligase Parkin, are a significant cause of early onset Parkinson's disease...
  2. ncbi Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism
    T Kitada
    Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan
    Nature 392:605-8. 1998
    ..Mutations in the newly identified gene appear to be responsible for the pathogenesis of AR-JP, and we have therefore named the protein product 'Parkin'.
  3. doi PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1
    Sven Geisler
    Laboratory of Functional Neurogenetics, Otfried Muller Strasse 27, 72076 Tubingen, Germany
    Nat Cell Biol 12:119-31. 2010
    Parkinson's disease is the most common neurodegenerative movement disorder. Mutations in PINK1 and PARKIN are the most frequent causes of recessive Parkinson's disease. However, their molecular contribution to pathogenesis remains unclear...
  4. pmc PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy
    Noriyuki Matsuda
    Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Setagaya Ku, Tokyo 156 8506, Japan
    J Cell Biol 189:211-21. 2010
    ..Recent identification of genes linked to familial forms of PD such as Parkin and PINK1 (PTEN-induced putative kinase 1) has revealed that ubiquitylation and mitochondrial integrity are key ..
  5. pmc Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin
    Atsushi Tanaka
    Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 191:1367-80. 2010
    ..b>Parkin, an E3 ubiquitin ligase that is mutated in monogenic forms of Parkinson's disease, was recently found to induce ..
  6. pmc Autoregulation of Parkin activity through its ubiquitin-like domain
    Viduth K Chaugule
    Protein Structure and Function Laboratory, Cancer Research UK, London Research Institute, London, UK
    EMBO J 30:2853-67. 2011
    b>Parkin is an E3-ubiquitin ligase belonging to the RBR (RING-InBetweenRING-RING family), and is involved in the neurodegenerative disorder Parkinson's disease...
  7. ncbi Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase
    H Shimura
    Department of Neurology, Juntendo University School of Medicine, Bunkyo ku, Tokyo, Japan
    Nat Genet 25:302-5. 2000
    ..We previously cloned PARK2, mutations of which cause AR-JP (ref. 2), but the function of the gene product, parkin, remains unknown...
  8. pmc Mitofusin 1 and mitofusin 2 are ubiquitinated in a PINK1/parkin-dependent manner upon induction of mitophagy
    Matthew E Gegg
    Department of Clinical Neurosciences, Institute of Neurology, University College London, London, UK
    Hum Mol Genet 19:4861-70. 2010
    ..Mutations in the Parkin and PINK1 genes are a cause of familial PD...
  9. pmc Broad activation of the ubiquitin-proteasome system by Parkin is critical for mitophagy
    Nickie C Chan
    Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    Hum Mol Genet 20:1726-37. 2011
    b>Parkin, an E3 ubiquitin ligase implicated in Parkinson's disease, promotes degradation of dysfunctional mitochondria by autophagy...
  10. ncbi Loss-of-function of human PINK1 results in mitochondrial pathology and can be rescued by parkin
    Nicole Exner
    Center for Integrated Protein Science Munich and Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University, 80336 Munich, Germany
    J Neurosci 27:12413-8. 2007
    ..Human parkin but not PD-associated mutants could rescue mitochondrial pathology in human cells like wild-type PINK1...
  11. pmc p62/SQSTM1 is required for Parkin-induced mitochondrial clustering but not mitophagy; VDAC1 is dispensable for both
    Derek Narendra
    Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke National Institutes of Health, Bethesda, MD, USA
    Autophagy 6:1090-106. 2010
    ..We recently demonstrated that the E3 ubiquitin ligase Parkin, which is linked to recessive forms of parkinsonism, causes a dramatic increase in mitophagy and a change in ..
  12. pmc p62/SQSTM1 cooperates with Parkin for perinuclear clustering of depolarized mitochondria
    Kei Okatsu
    Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, Setagaya Ku, Tokyo 156 8506, Japan
    Genes Cells 15:887-900. 2010
    PINK1 and Parkin were first identified as the causal genes responsible for familial forms of early-onset Parkinson's disease (PD), a prevalent neurodegenerative disorder...
  13. pmc Parkin is transcriptionally regulated by ATF4: evidence for an interconnection between mitochondrial stress and ER stress
    L Bouman
    Adolf Butenandt Institute, Neurobiochemistry, Ludwig Maximilians University, Schillerstrasse 44, Munich, Germany
    Cell Death Differ 18:769-82. 2011
    Loss of parkin function is responsible for the majority of autosomal recessive parkinsonism. Here, we show that parkin is not only a stress-protective, but also a stress-inducible protein...
  14. pmc Genetic etiology of Parkinson disease associated with mutations in the SNCA, PARK2, PINK1, PARK7, and LRRK2 genes: a mutation update
    Karen Nuytemans
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium
    Hum Mutat 31:763-80. 2010
    ..distinct DNA variants in five disease genes associated with familial Parkinson disease; alpha-synuclein (SNCA), parkin (PARK2), PTEN-induced putative kinase 1 (PINK1), DJ-1 (PARK7), and Leucine-rich repeat kinase 2 (LRRK2)...
  15. pmc Loss of PINK1 function promotes mitophagy through effects on oxidative stress and mitochondrial fission
    Ruben K Dagda
    Department of Pathology and Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    J Biol Chem 284:13843-55. 2009
    ..Autophagy/mitophagy served a protective role in limiting cell death, and overexpressing Parkin further enhanced this protective mitophagic response...
  16. pmc Nix is critical to two distinct phases of mitophagy, reactive oxygen species-mediated autophagy induction and Parkin-ubiquitin-p62-mediated mitochondrial priming
    Wen Xing Ding
    Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    J Biol Chem 285:27879-90. 2010
    ..b>Parkin is a ubiquitin-protein isopeptide ligase able to translocate to the mitochondria that are to be removed...
  17. ncbi Susceptibility to leprosy is associated with PARK2 and PACRG
    Marcelo T Mira
    McGill Centre for the Study of Host Resistance and Department of Human Genetics, McGill University, 1650 Cedar Avenue, Montreal, PQ H3G1A4, Canada
    Nature 427:636-40. 2004
    ..Variants in the regulatory region shared by PARK2 and PACRG therefore act as common risk factors for leprosy...
  18. pmc PINK1 is activated by mitochondrial membrane potential depolarization and stimulates Parkin E3 ligase activity by phosphorylating Serine 65
    Chandana Kondapalli
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
    Open Biol 2:120080. 2012
    ..We have discovered that insect PINK1 efficiently phosphorylates only one of these proteins, namely the E3 ligase Parkin. We have mapped the phosphorylation site to a highly conserved residue within the Ubl domain of Parkin at Ser(65)...
  19. pmc Parkinson's disease-associated kinase PINK1 regulates Miro protein level and axonal transport of mitochondria
    Song Liu
    Department of Pathology, Stanford University School of Medicine, Stanford, California, United States of America
    PLoS Genet 8:e1002537. 2012
    ..and facilitated autophagy of damaged mitochondria, effects previously associated with activation of the PINK1/Parkin pathway...
  20. pmc Parkin overexpression selects against a deleterious mtDNA mutation in heteroplasmic cybrid cells
    Der Fen Suen
    Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 107:11835-40. 2010
    ..The cytosolic E3 ligase, Parkin, commonly mutated in recessive familial parkinsonism, translocates to depolarized mitochondria and induces their ..
  21. pmc Parkin mono-ubiquitinates Bcl-2 and regulates autophagy
    Dong Chen
    Laboratory of Molecular Neuropathology, School of Life Sciences, University of Science and Technology of China, Chinese Academy of Sciences, Hefei, Anhui 230027, China
    J Biol Chem 285:38214-23. 2010
    b>Parkin is an E3 ubiquitin ligase that mediates the ubiquitination of protein substrates. The mutations in the parkin gene can lead to a loss of function of parkin and cause autosomal recessive juvenile onset parkinsonism...
  22. ncbi Parkin-induced mitophagy in the pathogenesis of Parkinson disease
    Derek Narendra
    Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
    Autophagy 5:706-8. 2009
    Knockout of the ubiquitin ligase Parkin, the gene product of the Parkinson associated Park2, leads to loss of mitochondrial integrity and function in Drosophila melanogaster...
  23. ncbi Diverse effects of pathogenic mutations of Parkin that catalyze multiple monoubiquitylation in vitro
    Noriyuki Matsuda
    Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo ku, Tokyo 113 8613
    J Biol Chem 281:3204-9. 2006
    Mutational dysfunction of PARKIN gene, which encodes a double RING finger protein and has ubiquitin ligase E3 activity, is the major cause of autosomal recessive juvenile Parkinsonism...
  24. ncbi Effect of endogenous mutant and wild-type PINK1 on Parkin in fibroblasts from Parkinson disease patients
    Aleksandar Rakovic
    Section of Clinical and Molecular Neurogenetics, Department of Neurology, University of Lubeck, 23562 Lübeck, Germany
    Hum Mol Genet 19:3124-37. 2010
    Mutations in the PTEN-induced putative kinase 1 (PINK1), a mitochondrial serine-threonine kinase, and Parkin, an E3 ubiquitin ligase, are associated with autosomal-recessive forms of Parkinson disease (PD)...
  25. pmc Identification of a novel Zn2+-binding domain in the autosomal recessive juvenile Parkinson-related E3 ligase parkin
    Ventzislava A Hristova
    Department of Biochemistry, University of Western Ontario, London, Ontario N6A 5C1, Canada
    J Biol Chem 284:14978-86. 2009
    Missense mutations in park2, encoding the parkin protein, account for approximately 50% of autosomal recessive juvenile Parkinson disease (ARJP) cases...
  26. pmc Phosphorylation of parkin by Parkinson disease-linked kinase PINK1 activates parkin E3 ligase function and NF-kappaB signaling
    Di Sha
    Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA
    Hum Mol Genet 19:352-63. 2010
    Mutations in PTEN-induced putative kinase 1 (PINK1) or parkin cause autosomal recessive forms of Parkinson disease (PD), but how these mutations trigger neurodegeneration is poorly understood and the exact functional relationship between ..
  27. ncbi Parkin ubiquitinates the alpha-synuclein-interacting protein, synphilin-1: implications for Lewy-body formation in Parkinson disease
    K K Chung
    Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Nat Med 7:1144-50. 2001
    ..Mutations in alpha-synuclein (A53T, A30P) and parkin cause familial Parkinson disease. Both these proteins are found in Lewy bodies...
  28. ncbi Alpha-synuclein and parkin contribute to the assembly of ubiquitin lysine 63-linked multiubiquitin chains
    Ellen W Doss-Pepe
    Department of Biochemistry, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA
    J Biol Chem 280:16619-24. 2005
    Mutations in alpha-synuclein, Parkin, and UCH-L1 cause heritable forms of Parkinson disease...
  29. ncbi Parkin mediates nonclassical, proteasomal-independent ubiquitination of synphilin-1: implications for Lewy body formation
    Kah Leong Lim
    Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    J Neurosci 25:2002-9. 2005
    It is widely accepted that the familial Parkinson's disease (PD)-linked gene product, parkin, functions as a ubiquitin ligase involved in protein turnover via the ubiquitin-proteasome system...
  30. pmc PINK1 autophosphorylation upon membrane potential dissipation is essential for Parkin recruitment to damaged mitochondria
    Kei Okatsu
    Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, Setagaya Ku, 156 8506, Japan
    Nat Commun 3:1016. 2012
    ..on the membrane potential (ΔΨm)-deficient mitochondria, where it recruits another familial PD gene product, Parkin, to ubiquitylate the damaged mitochondria...
  31. pmc Inhibition of mitochondrial fusion by α-synuclein is rescued by PINK1, Parkin and DJ-1
    Frits Kamp
    DZNE German Center for Neurodegenerative Diseases, Adolf Butenandt Institute, Biochemistry, Ludwig Maximilians University, Munich, Germany
    EMBO J 29:3571-89. 2010
    ..Finally, mitochondrial fragmentation induced by expression of αS is rescued by coexpression of PINK1, parkin or DJ-1 but not the PD-associated mutations PINK1 G309D and parkin Δ1-79 or by DJ-1 C106A.
  32. ncbi Parkin facilitates the elimination of expanded polyglutamine proteins and leads to preservation of proteasome function
    Yien Che Tsai
    Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD 21205, USA
    J Biol Chem 278:22044-55. 2003
    b>Parkin, the most commonly mutated gene in familial Parkinson's disease, encodes an E3 ubiquitin ligase...
  33. pmc Parkin functions as an E2-dependent ubiquitin- protein ligase and promotes the degradation of the synaptic vesicle-associated protein, CDCrel-1
    Y Zhang
    Departments of Neurology, Neuroscience, and Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287 0005, USA
    Proc Natl Acad Sci U S A 97:13354-9. 2000
    ..Mutations in Parkin, a ring-finger-containing protein of unknown function, are implicated in the pathogenesis of autosomal recessive ..
  34. pmc Mitochondrial function and morphology are impaired in parkin-mutant fibroblasts
    Heather Mortiboys
    Academic Neurology Unit, Medical School, University of Sheffield, Sheffield, United Kingdom
    Ann Neurol 64:555-65. 2008
    There are marked mitochondrial abnormalities in parkin-knock-out Drosophila and other model systems. The aim of our study was to determine mitochondrial function and morphology in parkin-mutant patients...
  35. ncbi A wide variety of mutations in the parkin gene are responsible for autosomal recessive parkinsonism in Europe. French Parkinson's Disease Genetics Study Group and the European Consortium on Genetic Susceptibility in Parkinson's Disease
    N Abbas
    INSERM U289, Hopital de la Salpetriere, 47 Boulevard de l Hopital, 75651 Paris Cedex 13, France
    Hum Mol Genet 8:567-74. 1999
    ..The gene responsible for AR-JP was recently identified and designated parkin. We have analysed the 12 coding exons of the parkin gene in 35 mostly European families with early onset autosomal ..
  36. pmc Bacterial artificial chromosome transgenic mice expressing a truncated mutant parkin exhibit age-dependent hypokinetic motor deficits, dopaminergic neuron degeneration, and accumulation of proteinase K-resistant alpha-synuclein
    Xiao hong Lu
    Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California 90095, USA
    J Neurosci 29:1962-76. 2009
    Recessive mutations in parkin are the most common cause of familial early-onset Parkinson's disease (PD)...
  37. doi PINK1 is recruited to mitochondria with parkin and associates with LC3 in mitophagy
    Sumihiro Kawajiri
    Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan
    FEBS Lett 584:1073-9. 2010
    ..PINK1 acts upstream of parkin, regulating mitochondrial integrity and functions...
  38. pmc Parkin selectively alters the intrinsic threshold for mitochondrial cytochrome c release
    Alison K Berger
    Neurology, Brigham and Women s Hospital, Boston, MA 02115, USA
    Hum Mol Genet 18:4317-28. 2009
    Autosomal-recessive mutations in the Parkin gene are the second most common cause of familial Parkinson's disease (PD)...
  39. ncbi Parkin accumulation in aggresomes due to proteasome impairment
    Eunsung Junn
    Genetic Pharmacology Unit, Experimental Therapeutics Branch, NINDS, National Institutes of Health, Bethesda, Maryland 20892 1406, USA
    J Biol Chem 277:47870-7. 2002
    ..Alpha-synuclein and Parkin are two of the proteins associated with inherited forms of PD and are found in Lewy bodies...
  40. pmc Parkin binds the Rpn10 subunit of 26S proteasomes through its ubiquitin-like domain
    Eri Sakata
    Department of Structural Biology and Biomolecular Engineering, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3 1 Tanabe dori, Mizuho ku, Nagoya 467 8603, Japan
    EMBO Rep 4:301-6. 2003
    b>Parkin, a product of the causative gene of autosomal-recessive juvenile parkinsonism (AR-JP), is a RING-type E3 ubiquitin ligase and has an amino-terminal ubiquitin-like (Ubl) domain...
  41. ncbi The C289G and C418R missense mutations cause rapid sequestration of human Parkin into insoluble aggregates
    Wen Jie Gu
    INSERM U 289, Hopital de la Salpetriere, 75013 Paris, France
    Neurobiol Dis 14:357-64. 2003
    Mutations in the parkin gene are responsible for autosomal recessive parkinsonism. The disease-linked missense mutations are highly concentrated in the RING-IBR-RING domains of Parkin...
  42. ncbi Parkin regulates Eg5 expression by Hsp70 ubiquitination-dependent inactivation of c-Jun NH2-terminal kinase
    Min Liu
    Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, Tianjin 300071, China
    J Biol Chem 283:35783-8. 2008
    ..In this study, we present the first evidence that the cellular Eg5 level is down-regulated by Parkin, an E3 ubiquitin ligase well known for its role in the development of Parkinson disease...
  43. pmc PARK2/PACRG polymorphisms and susceptibility to typhoid and paratyphoid fever
    S Ali
    Department of Infectious Diseases, Leiden University Medical Centre, The Netherlands
    Clin Exp Immunol 144:425-31. 2006
    ..Our findings suggest that this polymorphism in PARK2/PACRG plays a small but significant role in susceptibility to the intracellular pathogens S. typhi and S. paratyphi...
  44. ncbi Ubiquitination of a new form of alpha-synuclein by parkin from human brain: implications for Parkinson's disease
    H Shimura
    Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    Science 293:263-9. 2001
    ..forms of PD are caused by autosomal dominant mutations in alpha-synuclein or by autosomal recessive mutations in parkin, an E3 ubiquitin ligase...
  45. pmc Chromosome 6-linked autosomal recessive early-onset Parkinsonism: linkage in European and Algerian families, extension of the clinical spectrum, and evidence of a small homozygous deletion in one family. The French Parkinson's Disease Genetics Study Group
    J Tassin
    INSERM U289, Hôpital de la Salpêtière, Paris, France
    Am J Hum Genet 63:88-94. 1998
    ..The clinical spectrum of the disease in our families, with age at onset <=58 years and the presence of painful dystonia in some patients, is broader than that reported previously...
  46. ncbi Interaction between parkin and mutant glucocerebrosidase variants: a possible link between Parkinson disease and Gaucher disease
    Idit Ron
    Department of Cell Research and Immunology, Tel Aviv University, Ramat Aviv 69978, Israel
    Hum Mol Genet 19:3771-81. 2010
    ..One of the genes involved in PD is PARK2, encoding the E3 ubiquitin ligase parkin. Parkin functions in the ERAD of misfolded ER proteins, and it is upregulated by unfolded protein response...
  47. ncbi Familial-associated mutations differentially disrupt the solubility, localization, binding and ubiquitination properties of parkin
    Sathya R Sriram
    Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Hum Mol Genet 14:2571-86. 2005
    Mutations in parkin are largely associated with autosomal recessive juvenile parkinsonism...
  48. ncbi Relative sensitivity of parkin and other cysteine-containing enzymes to stress-induced solubility alterations
    Esther S P Wong
    Neurodegeneration Research Laboratory and Parkinson s Disease and Movement Disorders Center, National Neuroscience Institute, Singapore 308433
    J Biol Chem 282:12310-8. 2007
    Loss of parkin function is a predominant cause of familial Parkinsonism. Emerging evidence also suggests that parkin expression variability may confer a risk for sporadic Parkinson disease...
  49. ncbi Features of the parkin/ariadne-like ubiquitin ligase, HHARI, that regulate its interaction with the ubiquitin-conjugating enzyme, Ubch7
    H C Ardley
    Molecular Medicine Unit and the Leeds Dental Institute, University of Leeds, Clinical Sciences Building, St James s University Hospital, Leeds LS9 7TF, United Kingdom
    J Biol Chem 276:19640-7. 2001
    ..for by the highly homologous RING finger domains of either of the ubiquitin-protein ligase components c-CBL or Parkin, despite their similarity in structure and their independent capabilities to bind UbcH7...
  50. pmc Parkin-mediated monoubiquitination of the PDZ protein PICK1 regulates the activity of acid-sensing ion channels
    Monica Joch
    Centre for Neuronal Survival and Cell Biology of Excitable Tissues, Montreal Neurological Institute, McGill University, Montreal, Quebec, H3A 2B4, Canada
    Mol Biol Cell 18:3105-18. 2007
    Mutations in the parkin gene result in an autosomal recessive juvenile-onset form of Parkinson's disease. As an E3 ubiquitin-ligase, parkin promotes the attachment of ubiquitin onto specific substrate proteins...
  51. pmc Parkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex promoting unfolded protein degradation
    Hui Xiong
    Burnham Institute for Medical Research, 10901 N Torrey Pines Road, La Jolla, CA 92037, USA
    J Clin Invest 119:650-60. 2009
    Mutations in PARKIN, pten-induced putative kinase 1 (PINK1), and DJ-1 are individually linked to autosomal recessive early-onset familial forms of Parkinson disease (PD)...
  52. ncbi Parkin protects human dopaminergic neuroblastoma cells against dopamine-induced apoptosis
    Houbo Jiang
    Department of Physiology and Biophysics, State University of New York at Buffalo, 14214, USA
    Hum Mol Genet 13:1745-54. 2004
    ..Among the five PD-linked genes identified so far, parkin, a protein-ubiquitin E3 ligase, appears to be the most prevalent genetic factor in PD...
  53. pmc Nitrosative stress linked to sporadic Parkinson's disease: S-nitrosylation of parkin regulates its E3 ubiquitin ligase activity
    Dongdong Yao
    Center for Neuroscience and Aging, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 101:10810-4. 2004
    ..In the case of autosomal recessive-juvenile Parkinsonism, mutation in the E3 ubiquitin ligase protein parkin is linked to death of dopaminergic neurons...
  54. ncbi Dopamine covalently modifies and functionally inactivates parkin
    Matthew J LaVoie
    Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital, 77 Avenue Louis Pasteur, HIM 7th Floor, Boston, Massachusetts 02115, USA
    Nat Med 11:1214-21. 2005
    Inherited mutations in PARK2, the gene encoding parkin, cause selective degeneration of catecholaminergic neurons in the substantia nigra and locus coeruleus of the brainstem, resulting in early-onset parkinsonism...
  55. ncbi Accumulation of the authentic parkin substrate aminoacyl-tRNA synthetase cofactor, p38/JTV-1, leads to catecholaminergic cell death
    Han Seok Ko
    Institute for Cell Engineering, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    J Neurosci 25:7968-78. 2005
    Autosomal-recessive juvenile parkinsonism (AR-JP) is caused by loss-of-function mutations of the parkin gene...
  56. pmc Transcriptional repression of p53 by parkin and impairment by mutations associated with autosomal recessive juvenile Parkinson's disease
    Cristine Alves da Costa
    Institut de Pharmacologie Moleculaire et Cellulaire, UMR6097 CNRS UNSA, Equipe labellisée Fondation pour la Recherche Médicale, 660 route des Lucioles, 06560, Valbonne, France
    Nat Cell Biol 11:1370-5. 2009
    Mutations of the ubiquitin ligase parkin account for most autosomal recessive forms of juvenile Parkinson's disease (AR-JP). Several studies have suggested that parkin possesses DNA-binding and transcriptional activity...
  57. ncbi Biochemical analysis of Parkinson's disease-causing variants of Parkin, an E3 ubiquitin-protein ligase with monoubiquitylation capacity
    Cornelia Hampe
    Neurologie et Thérapeutique Expérimentale, INSERM U679 Université Pierre and Marie Curie, Paris, France
    Hum Mol Genet 15:2059-75. 2006
    Mutations in the parkin gene, encoding an E3 ubiquitin-protein ligase, are a frequent cause of autosomal recessive parkinsonism and are also involved in sporadic Parkinson's disease...
  58. ncbi Influence of heterozygosity for parkin mutation on onset age in familial Parkinson disease: the GenePD study
    Mei Sun
    Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA
    Arch Neurol 63:826-32. 2006
    The PARK2 gene at 6q26 encodes parkin, whose inactivation is implicated in an early-onset autosomal recessive form of Parkinson disease (PD).
  59. ncbi Leucine-Rich Repeat Kinase 2 interacts with Parkin, DJ-1 and PINK-1 in a Drosophila melanogaster model of Parkinson's disease
    Katerina Venderova
    Ottawa Health Research Institute, Neuroscience Research Institute, Ontario, Canada
    Hum Mol Genet 18:4390-404. 2009
    ..transgenic flies, various indices of the eye and dopaminergic survival were modified in a complex fashion by a concomitant expression of PINK1, DJ-1 or Parkin. This evidence suggests a genetic interaction between these PD-relevant genes.
  60. pmc Mutations in PINK1 and Parkin impair ubiquitination of Mitofusins in human fibroblasts
    Aleksandar Rakovic
    Section of Clinical and Molecular Neurogenetics, Department of Neurology, University of Lubeck, Lubeck, Germany
    PLoS ONE 6:e16746. 2011
    PINK1 and Parkin mutations cause recessive Parkinson's disease (PD)...
  61. ncbi Rare heterozygous parkin variants in French early-onset Parkinson disease patients and controls
    S Lesage
    J Med Genet 45:43-6. 2008
    Mutations in the parkin gene cause autosomal recessive early-onset parkinsonism. The effect of single heterozygous mutations in parkin is still unclear...
  62. ncbi Parkin protects against neurotoxicity in the 6-hydroxydopamine rat model for Parkinson's disease
    Linda Vercammen
    Laboratory for Neurobiology and Gene Therapy, Molecular Medicine, K U Leuven, Kapucijnenvoer 33 VCTB 5, B 3000 Leuven, Flanders, Belgium
    Mol Ther 14:716-23. 2006
    ..The gene product, parkin, is an E3 ligase of the ubiquitin-proteasome pathway involved in protein degradation...
  63. doi Parkin analysis in early onset Parkinson's disease
    Francesca Sironi
    Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy
    Parkinsonism Relat Disord 14:326-33. 2008
    We analysed the parkin gene in a large consecutive series (146) of unrelated early onset Parkinson's disease (onset ?40 years of age) patients. Twelve cases (8...
  64. doi Bilateral subthalamic stimulation in Parkin and PINK1 parkinsonism
    E Moro
    Movement Disorder Centre, Toronto Western Hospital, University of Toronto, Ontario, Canada
    Neurology 70:1186-91. 2008
    ....
  65. ncbi Role of parkin mutations in 111 community-based patients with early-onset parkinsonism
    Martin Kann
    Department of Neurology, Medical University of Lubeck, Lubeck, Germany
    Ann Neurol 51:621-5. 2002
    Early-onset parkinsonism is frequently reported in connection with mutations in the parkin gene...
  66. doi Screening PARK genes for mutations in early-onset Parkinson's disease patients from Queensland, Australia
    George D Mellick
    Eskitis Institute for Cellular and Molecular Therapies, Griffith University, Nathan, QLD 4111, Australia
    Parkinsonism Relat Disord 15:105-9. 2009
    ..The entire coding region of the PRKN (MIM 602544), DJ-1 (MIM 602533) and PINK1 (MIM 698309) genes, and exon 41 of the LRRK2 gene (MIM 609007) were ..
  67. pmc Solution structure of the E3 ligase HOIL-1 Ubl domain
    Steven A Beasley
    Department of Biochemistry, University of Western Ontario, London, Ontario N6A 5C1, Canada
    Protein Sci 21:1085-92. 2012
    The E3 ligases HOIL-1 and parkin are each comprised of an N-terminal ubiquitin-like (Ubl) domain followed by a zinc-binding region and C-terminal RING-In-between-RING-RING domains...
  68. ncbi Parkin mutations and phenotypic features in Czech patients with early-onset Parkinson's disease
    Ondrej Fiala
    Department of Neurology, 1st Medical Faculty and General Teaching Hospital, Charles University, Prague, Czech Republic
    Neuro Endocrinol Lett 31:187-92. 2010
    Mutations in several genes such as parkin can be detected in up to 20% of patients with early-onset Parkinson's disease (EOPD)...
  69. ncbi Identification of far upstream element-binding protein-1 as an authentic Parkin substrate
    Han Seok Ko
    Institute for Cell Engineering, Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    J Biol Chem 281:16193-6. 2006
    ..multifunctional protein type 2 was recently identified as an authentic substrate of the ubiquitin E3 ligase, parkin, a gene associated with autosomal recessive juvenile parkinsonism...
  70. ncbi Does parkin play a role in the peripheral nervous system? A family report
    Giovanni Abbruzzese
    Department of Neuroscience, Ophthalmology and Genetics, Section of Neurology, University of Genova, Italy
    Mov Disord 19:978-81. 2004
    Two genes were identified for autosomal recessive forms of early onset Parkinson's disease: parkin and DJ-1...
  71. ncbi CHIP is associated with Parkin, a gene responsible for familial Parkinson's disease, and enhances its ubiquitin ligase activity
    Yuzuru Imai
    Laboratory for Motor System Neurodegeneration, RIKEN Brain Science Institute, Saitama 351 0198, Japan
    Mol Cell 10:55-67. 2002
    Unfolded Pael receptor (Pael-R) is a substrate of the E3 ubiquitin ligase Parkin. Accumulation of Pael-R in the endoplasmic reticulum (ER) of dopaminergic neurons induces ER stress leading to neurodegeneration...
  72. ncbi Parkin disrupts the alpha-synuclein/dopamine transporter interaction: consequences toward dopamine-induced toxicity
    Anna Moszczynska
    Department of Neuroscience, Centre for Addiction and Mental Health, Clarke Division, 250 College Street, Toronto, ON M5T 1R8, Canada
    J Mol Neurosci 32:217-27. 2007
    ..In the present study, we report that parkin, an E2-dependent E3 protein ubiquitin ligase associated with recessive early onset Parkinson's disease, exerts a ..
  73. ncbi Detection of compound heterozygous deletions in the parkin gene of fibroblasts in patients with autosomal recessive hereditary parkinsonism (PARK2)
    Kazuhiro Nakaso
    Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, 36 1, Nishimachi, Yonago 683 8504, Japan
    Neurosci Lett 400:44-7. 2006
    Mutations in the parkin gene are a common cause of autosomal recessive, juvenile or early onset parkinsonism (PARK2)...
  74. ncbi Association between early-onset Parkinson's disease and mutations in the parkin gene
    C B Lücking
    INSERM Unité 289, Hopital de la Salpetriere, Paris
    N Engl J Med 342:1560-7. 2000
    Mutations in the parkin gene have recently been identified in patients with early-onset Parkinson's disease, but the frequency of the mutations and the associated phenotype have not been assessed in a large series of patients.
  75. ncbi Parkin mutations in a patient with hemiparkinsonism-hemiatrophy: a clinical-genetic and PET study
    P P Pramstaller
    Department of Neurology, Regional General Hospital, Bolzano Bozen, Italy
    Neurology 58:808-10. 2002
    ..Genetic analysis revealed a missense mutation (Arg275Trp) and a duplication of exon 7 of parkin. The complementary metabolic and receptor pattern of PET ligands corresponded to that typically found in ..
  76. ncbi Caspase-1 and caspase-8 cleave and inactivate cellular parkin
    Soren Kahns
    Department of Molecular Biology, University of Aarhus, DK 8000 Aarhus C, Denmark
    J Biol Chem 278:23376-80. 2003
    Lesions in the parkin gene cause early onset Parkinson's disease by a loss of dopaminergic neurons, thus demonstrating a vital role for parkin in the survival of these neurons...
  77. ncbi Parkin directly modulates 26S proteasome activity
    Ji Won Um
    Department of Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea
    J Neurosci 30:11805-14. 2010
    ..While proteasome dysfunction is observed in PD, diverse mutations in the parkin gene are linked to early-onset autosomal-recessive forms of familial PD...
  78. ncbi Parkin interacts with LIM Kinase 1 and reduces its cofilin-phosphorylation activity via ubiquitination
    Meng K Lim
    Department of Molecular Biology, Keio University School of Medicine, 35 Shinanomachi, Tokyo, Japan
    Exp Cell Res 313:2858-74. 2007
    Mutations in the PARKIN (PARK2) gene have been found in the majority of early-onset familial Parkinson's disease (PD) patients with autosomal recessive juvenile parkinsonism (ARJP)...
  79. pmc Differential interaction of the E3 ligase parkin with the proteasomal subunit S5a and the endocytic protein Eps15
    Susan S Safadi
    Department of Biochemistry, The University of Western Ontario, London, Ontario N6A 5C1, Canada
    J Biol Chem 285:1424-34. 2010
    b>Parkin is a multidomain E3 ligase associated with autosomal recessive Parkinson disease. The N-terminal ubiquitin-like domain (Ubld) of parkin functions with the S5a proteasomal subunit, positioning substrate proteins for degradation...
  80. pmc Phosphorylation by the c-Abl protein tyrosine kinase inhibits parkin's ubiquitination and protective function
    Han Seok Ko
    Neuroregeneration Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 107:16691-6. 2010
    Mutations in PARK2/Parkin, which encodes a ubiquitin E3 ligase, cause autosomal recessive Parkinson disease (PD)...
  81. pmc Localization of a gene for an autosomal recessive form of juvenile Parkinsonism to chromosome 6q25.2-27
    H Matsumine
    Department of Neurology, Juntendo University School of Medicine, Bunkyo, Tokyo, Japan
    Am J Hum Genet 60:588-96. 1997
    ..Delineation of the AR-JP gene will be an important step toward our understanding of the molecular mechanism underlying selective degeneration of the nigral neurons...
  82. ncbi Parkin is a component of an SCF-like ubiquitin ligase complex and protects postmitotic neurons from kainate excitotoxicity
    John F Staropoli
    Department of Pathology, Center for Neurobiology and Behavior, Taub Institute, College of Physicians and Surgeons, Columbia University, 15 403, 630 West 168th Street, New York, NY 10032, USA
    Neuron 37:735-49. 2003
    Mutations in parkin, which encodes a RING domain protein associated with ubiquitin ligase activity, lead to autosomal recessive Parkinson's disease characterized by midbrain dopamine neuron loss...
  83. ncbi Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin-protein ligase activity
    Y Imai
    Laboratory for Motor System Neurodegeneration, RIKEN Brain Science Institute BSI, Saitama 351 0198, Japan
    J Biol Chem 275:35661-4. 2000
    Autosomal recessive juvenile parkinsonism (AR-JP) is caused by mutations in the parkin gene...
  84. ncbi Novel mutations, pseudo-dominant inheritance, and possible familial affects in patients with autosomal recessive juvenile parkinsonism
    M Maruyama
    Department of Neurology, Brain Research Institute, Niigata University, Japan
    Ann Neurol 48:245-50. 2000
    ..In 1 family, in which an autosomal dominant mode of inheritance was suspected, multiple mutant alleles were identified. Although a wide range of ages at onset was observed, there was no correlation between age at onset and genotype...
  85. pmc How does parkin ligate ubiquitin to Parkinson's disease?
    Philipp J Kahle
    Laboratory of Alzheimer s and Parkinson s Disease Research, Department of Biochemistry, Ludwig Maximilians University of Munich, Schillerstrasse 44, 80336 Munchen, Germany
    EMBO Rep 5:681-5. 2004
    Recessive mutations in the human PARKIN gene are the most common cause of hereditary parkinsonism, which arises from the degeneration of dopaminergic neurons in the substantia nigra...
  86. pmc Parkin reverses intracellular beta-amyloid accumulation and its negative effects on proteasome function
    Kenneth M Rosen
    Department of Neurology, Tufts University School of Medicine, Boston, Massachusetts, USA
    J Neurosci Res 88:167-78. 2010
    ..The E3 ubiquitin ligase Parkin targets several proteins for UPS degradation, and Parkin mutations are the major cause of autosomal recessive ..
  87. ncbi Heterozygosity for a mutation in the parkin gene leads to later onset Parkinson disease
    T Foroud
    Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, USA
    Neurology 60:796-801. 2003
    The vast majority of the parkin mutations previously identified have been found in individuals with juvenile or early onset PD. Previous screening of later onset PD cohorts has not identified substantial numbers of parkin mutations.
  88. ncbi Parkin enhances mitochondrial biogenesis in proliferating cells
    Yukiko Kuroda
    Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, 3 18 15 Kuramoto cho, Tokushima 770 8503, Japan
    Hum Mol Genet 15:883-95. 2006
    We describe a novel function of parkin, a RING protein, which is elaborately involved in mitochondrial biogenesis. Parkin was located within the mitochondrial organelle of proliferating cells...
  89. ncbi LRRK2 gene in Parkinson disease: mutation analysis and case control association study
    C Paisan-Ruiz
    National Institute on Aging, National Institutes of Health, Porter Neuroscience Research Center, Bethesda, MD, USA
    Neurology 65:696-700. 2005
    In addition to the four well-confirmed genes linked to early-onset Parkinson disease (PD) (SNCA, PARKIN, DJ-1, and PINK1), mutations in the leucine-rich repeat kinase 2 gene (LRRK2) have recently been identified in families with autosomal ..
  90. pmc Parkin localizes to the Lewy bodies of Parkinson disease and dementia with Lewy bodies
    Michael G Schlossmacher
    Department of Neurology, Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Am J Pathol 160:1655-67. 2002
    Mutations in alpha-synuclein (alpha S) and parkin cause heritable forms of Parkinson disease (PD)...
  91. ncbi Parkin suppresses dopaminergic neuron-selective neurotoxicity induced by Pael-R in Drosophila
    Yufeng Yang
    Laboratory of Developmental Neurobiology, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Neuron 37:911-24. 2003
    b>Parkin, an E3 ubiquitin ligase that degrades proteins with aberrant conformations, is associated with autosomal recessive juvenile Parkinsonism (AR-JP). The molecular basis of selective neuronal death in AR-JP is unknown...
  92. ncbi Pathogenic mutations inactivate parkin by distinct mechanisms
    Iris H Henn
    Department of Cellular Biochemistry, Max Planck Institute for Biochemistry, Martinsried, Germany
    J Neurochem 92:114-22. 2005
    Loss of parkin function is the major cause of autosomal recessive Parkinson's disease (ARPD)...
  93. doi Genotypic and phenotypic characteristics of Dutch patients with early onset Parkinson's disease
    Maria G Macedo
    Section of Medical Genomics, Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands
    Mov Disord 24:196-203. 2009
    Early onset Parkinson's disease (EOPD) has been associated with mutations in the Parkin, DJ-1, PINK1, LRRK2, and SNCA genes...
  94. ncbi Transcription factor single-minded 2 (SIM2) is ubiquitinated by the RING-IBR-RING-type E3 ubiquitin ligases
    Michiyo Okui
    Department of Molecular Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku ku, Tokyo 160 8582, Japan
    Exp Cell Res 309:220-8. 2005
    ..four different E3 ubiquitin ligases, SIM2 was immunoprecipitated with the RING-IBR-RING-type E3 ubiquitin ligases, Parkin and HHARI, but it was not immunoprecipitated with other E3 ligases, such as one RING-type Siah-1 and the PHD type ..
  95. ncbi Parkin phosphorylation and modulation of its E3 ubiquitin ligase activity
    Ayako Yamamoto
    Laboratory of Alzheimer s and Parkinson s Disease Research, Department of Metabolic Biochemistry, Ludwig Maximilians University, 80336 Munich, Germany
    J Biol Chem 280:3390-9. 2005
    Mutations in the PARKIN gene are the most common cause of hereditary parkinsonism...
  96. ncbi Functional modulation of parkin through physical interaction with SUMO-1
    Ji Won Um
    Department of Biology, College of Science, Yonsei University, Seoul, Korea
    J Neurosci Res 84:1543-54. 2006
    ..Mutations in the parkin gene, which encodes for E3 ubiquitin ligase, have been implicated in autosomal recessive juvenile parkinsonism, an ..
  97. pmc Relative high frequency of the c.255delA parkin gene mutation in Spanish patients with autosomal recessive parkinsonism
    E Munoz
    Movemente Disorder Unit, Neurology Service, Institut Clinic de Malalties del Sistema Nervios, Villarroel 170, 08036 Barcelona, Spain
    J Neurol Neurosurg Psychiatry 73:582-4. 2002
    Autosomal recessive juvenile parkinsonism is a neurodegenerative disorder associated with mutations in the parkin gene.
  98. ncbi Mutational analysis of parkin gene by denaturing high-performance liquid chromatography (DHPLC) in essential tremor
    Simona Pigullo
    Department of Neurosciences, Ophthalmology and Genetics, Section of Medical Genetics, University of Genoa c o DIMI, Viale Benedetto XV 6, 16132 Genoa, Italy
    Parkinsonism Relat Disord 10:357-62. 2004
    To evaluate the relationship between point mutations within the parkin gene and essential tremor (ET).
  99. ncbi Low frequency of Parkin, Tyrosine Hydroxylase, and GTP Cyclohydrolase I gene mutations in a Danish population of early-onset Parkinson's Disease
    J M Hertz
    Department of Clinical Genetics, Aarhus University Hospital, Denmark
    Eur J Neurol 13:385-90. 2006
    Autosomal recessive Parkinson's disease (PD) with early-onset may be caused by mutations in the parkin gene (PARK2)...
  100. doi PARK2 mutations and clinical features in a Chinese population with early-onset Parkinson's disease
    Daniel Kam Yin Chan
    Department of Aged Care and Rehabilitation, Bankstown Hospital, Bankstown, NSW, Australia
    J Neural Transm 115:715-9. 2008
    ..A compound heterozygous mutation within two sisters with significant differences in age of onset and phenotypic manifestations suggest that modifier affects may be present in this family...
  101. ncbi Restless legs syndrome, rapid eye movement sleep behavior disorder, and hypersomnia in patients with two parkin mutations
    Nadege Limousin
    Unité des Pathologies du sommeil and UMR 975, Universite Paris 6, Hopital Pitie Salpetriere, Assistance Publique Hôpitaux de, Paris, France
    Mov Disord 24:1970-6. 2009
    b>Parkin gene mutations cause a juvenile parkinsonism. Patients with these mutations may commonly exhibit REM sleep behaviour disorders, but other sleep problems (insomnia, sleepiness, restless legs syndrome) have not been studied...

Research Grants126 found, 100 shown here

  1. The Roles of a-Synuclein and Parkin in Parkinson Disease
    Michael Schlossmacher; Fiscal Year: 2005
    ..The PARK2 gene encodes parkin, an E3 ubiquitin ligase...
  2. Proteome-wide analysis of E3 ubiquitin ligase-substrate relationships
    LEA STARITA; Fiscal Year: 2007
    ..tumor suppressor BRCA1 (breast cancer-1) and the protein mutated in early onset Parkinson's disease Parkin acting as ubiquitin ligases...
  3. Regulation of Osteoblast Function by Megakaryocytes: Key Signaling Proteins
    Melissa A Kacena; Fiscal Year: 2012
    ..Identifying the pathways that lead to enhanced bone volume in vivo will lead to the development of novel therapeutic approaches that stimulate bone formation for the treatment of osteoporosis and other bone loss diseases. ..
  4. REGULATION OF DEFENSE SIGNALING IN TOMATO
    Gregg A Howe; Fiscal Year: 2012
    ....
  5. Mechanisms and Relevance of Sodium Transport Regulation by AMPK
    Kenneth R Hallows; Fiscal Year: 2013
    ....
  6. Proteolytic silencing of cancer targets using engineered ubiquitin ligases
    Matthew P DeLisa; Fiscal Year: 2013
    ....
  7. Cell Cycle Regulation and Adult T Cell Leukemia
    Chou Zen Giam; Fiscal Year: 2013
    ..The study will provide molecular insights that can lead to the development of treatment strategies for human cancer ..
  8. Role of Parkinson's disease gene PARK2 in GBM oncogenesis and genomic instability
    TIMOTHY AN THY CHAN; Fiscal Year: 2013
    ..abstract_text> ..
  9. The Role of CRL4-Cdt2 E3 Ubiquitin Ligase in Genomic Stability and Cancer
    TAREK A ABBAS; Fiscal Year: 2012
    ..The results will advance our understanding of how to exploit the regulated process of protein ubiquitylation and proteolysis for cancer intervention purposes. ..
  10. The Role of CRL4-Cdt2 E3 Ubiquitin Ligase in Genomic Stability and Cancer
    TAREK A ABBAS; Fiscal Year: 2013
    ..The results will advance our understanding of how to exploit the regulated process of protein ubiquitylation and proteolysis for cancer intervention purposes. ..
  11. The Roles of a-Synuclein and Parkin in Parkinson Disease
    Michael Schlossmacher; Fiscal Year: 2004
    ..The PARK2 gene encodes parkin, an E3 ubiquitin ligase...
  12. Misregulation of receptor tyrosine kinase signaling in PKD
    Jordan A Kreidberg; Fiscal Year: 2013
    ..Failure to ubquitinate c-Met is due to sequestration of the E3 ubiquitin ligase c-Cbl by 31 integrin in the Golgi apparatus. This grant will investigate the roles of c-Cbl, c-Met and protein glycosylation in the pathogenesis of PKD. ..
  13. Post-translational regulation of MLL in leukemogenesis
    ANDREW GEORGE MUNTEAN; Fiscal Year: 2013
    ..These studies focus on the MLL-PAFc interaction and ubiquitination of MLL which are directly relevant to MLL and HOX dependent leukemias and may prove as effective therapeutic targets. ..
  14. Post-translational regulation of MLL in leukemogenesis
    ANDREW GEORGE MUNTEAN; Fiscal Year: 2012
    ..These studies focus on the MLL-PAFc interaction and ubiquitination of MLL which are directly relevant to MLL and HOX dependent leukemias and may prove as effective therapeutic targets. ..
  15. Enhancement of Medullary Erythropoiesis during Anemia by Trib3
    David Kuhrt; Fiscal Year: 2013
    ..This trainin plan is designed to advance impacting first author papers and expertise as a new independent investigator. ..
  16. Hypoxia and Anticancer Drug Action
    Garth Powis; Fiscal Year: 2013
    ..abstract_text> ..
  17. Mechanisms of novel cancer targets in ARF-mediated tumor suppression
    Wei Gu; Fiscal Year: 2013
    ..In Aim 2, to validate whether ARF-BP1 is indeed a potential cancer target, we will use the ARF-BP1 mutant mice to examine whether inhibition of ARF-BP1 suppresses tumorigenesis in vivo in a manner reminiscent of ARF activation. ..
  18. Mechanistic validation of SCF E3 ligase as a cancer and radiosensitizing target
    Yi Sun; Fiscal Year: 2013
    ..This study will validate SCF E3 ubiquitin ligase as an anticancer and radiosensitizing target and MLN4924, a newly discovered SCF E3 ligase inhibitor, as a tumor-selective and radiosensitizing agent for cancer therapy. ..
  19. B-RAF Regulation of the Cell Cycle in Melanoma
    Andrew E Aplin; Fiscal Year: 2013
    ..At the completion of our experiments, we aim to have identified new targets for therapeutic intervention to prevent aberrant melanoma cell proliferation. ..
  20. The role of MID1/MID2 in regulating epithelial adhesion
    CATHERINE KOTO; Fiscal Year: 2013
    ....
  21. PROTEASOME AND PARKIN AS DRUG TARGETS AGAINST METHAMPHETAMINE TOXICITY
    Anna Moszczynska; Fiscal Year: 2013
    ..in the METH-exposed rat brain and to determine whether two components of this system, proteasome and the E3 ligase parkin, are potential pharmaceutical targets that can be used to promote [survival and recovery] of dopaminergic ..
  22. Manipulation of host immunity by a bacterial E3 ubiquitin ligase
    Gregory B Martin; Fiscal Year: 2013
    ..The knowledge gained will contribute to strategies to lessen the impact of bacterial diseases of importance to both agriculture and human health. ..
  23. E3 Ubiquitin Ligase Functions in Enveloped Virus Budding
    ANDREW PAUL NORGAN; Fiscal Year: 2010
    ..The insights gained from this research will have broad application to the study of other enveloped viruses, including Epstein- Barr virus. Human T-cell Lymophotropic virus. Influenza virus, and others. ..
  24. Elucidating a molecular pathway for synaptic vesicle maintenance and degradation
    CLARISSA LEIGH WAITES; Fiscal Year: 2013
    ..Together, these studies will provide novel insights into how SV-stasis is maintained, and how its dysregulation contributes to synapse degeneration and the etiology of neurodegenerative disease. ..
  25. Histone chaperones and epigenetic silencing
    Zhiguo Zhang; Fiscal Year: 2013
    ....
  26. Regulation, signaling, and dynamics of glucan phosphatases.
    Matthew S Gentry; Fiscal Year: 2013
    ..Completion of this work will yield a better comprehension of these complex events and will produce therapeutic insights for epilepsy and neurodegeneration. ..
  27. New insights into the role of the Fbw7 tumor suppressor in senescence and aging
    Hiroyuki Inuzuka; Fiscal Year: 2013
    ..We expect this will provide evidence toward the rationale for using mTOR pharmacological intervention in personalized medicine for age-related diseases. ..
  28. Cellular Stress Response Signaling Pathways
    MICHAEL BARRY KASTAN; Fiscal Year: 2013
    ....
  29. Neurobiological Mechanism of 15q11-13 Duplication Autism Spectrum Disorder
    Matthew P Anderson; Fiscal Year: 2013
    ..The novel molecular insights and genetic tools will facilitate development of treatments for these life-long behavioral disabilities. ..
  30. Identifying c-Cbl as a critical point of intervention in glioblastoma multiforme
    JENNIFER LYNN STRIPAY; Fiscal Year: 2013
    ..Our overarching goal is to identify novel roles for both FAK and HSP90 and confirm the importance of c-Cbl inhibition in glioma biology to guide development of innovative therapeutics. ..
  31. Role of DNA damage in the early steps of HSV infection and latency in neurons
    Matthew D Weitzman; Fiscal Year: 2013
    ..Knowledge of HSV-1 neuronal latency will suggest novel targets for developing antivirals against this significant human pathogen. ..
  32. Novel regulation of PI3K/Akt to direct targeted breast cancer therapies
    Wenyi Wei; Fiscal Year: 2013
    ..Instead, our studies will inform the use of Cdk2, Skp2 and Akt inhibitors for targeted therapy to achieve optimal treatment efficacy in the clinic. ..
  33. Identification of the protein homeostasis network that controls the quality contr
    CHRISTINE MARIE LIVINGSTON; Fiscal Year: 2013
    ....
  34. Molecular control of spermatogonial stem cell fate for achieving cell therapy
    Christina Tenenhaus Dann; Fiscal Year: 2013
    ....
  35. Epigenetic Regulation of Ube3a as a Treatment for Angelman Syndrome
    Mark J Zylka; Fiscal Year: 2013
    ..e. Ube3a unsilencing). Our research could lead to the first pharmacological treatment for Angelman syndrome (an autism spectrum disorder), and indeed for any disorder caused by mutation of an imprinted gene. ..
  36. Understanding the Function of TRIM 24 in Mammary Epithelial Cells
    AUNDRIETTA DE VAN DUNCAN; Fiscal Year: 2013
    ..This information can be value in the potential use of TRIM24 as a diagnostic marker and therapeutic target. ..
  37. The Role of Type III TGF-beta Receptor in the Fibrotic Tumor Stroma
    RACHEL HESLER; Fiscal Year: 2013
    ..These studies will determine the role of T?RIII in myofibroblast activation and ECM secretion, facilitating targeting of the fibrotic stroma for the treatment of these deadly cancers. ..
  38. VHL tumor suppressor gene and the initiation of renal cell carcinoma
    Tien Hsu; Fiscal Year: 2013
    ..Aim 3. To elucidate the mechanism of inflammation in VHL mutant kidney. Aim 4. To profile the gene expression pattern associated with VHL tumor progression. ..
  39. Cytochrome c Degradation: A Mechanism to Restrict Apoptosis in Postmitotic Cells
    Mohanish Deshmukh; Fiscal Year: 2013
    ....
  40. The Role of ATF3 in the DNA Damage Response
    Chunhong Yan; Fiscal Year: 2013
    ....
  41. Structural studies of cullin-based ubiquitin ligases
    Ning Zheng; Fiscal Year: 2010
    ....
  42. Structural studies of cullin-based ubiquitin ligases
    Ning Zheng; Fiscal Year: 2009
    ....
  43. BubRI in Cancer and Aging
    Jan M van Deursen; Fiscal Year: 2013
    ....
  44. Regulation of hematopoietic stem cell maintenance and survival by NKAP
    Virginia Smith Shapiro; Fiscal Year: 2013
    ....
  45. Function of Cerebral Cavernous Malformation Proteins
    Gary L Johnson; Fiscal Year: 2013
    ..iii. The ability to isolate differentiated ECs from patient-specific hiPSCs for constructing in vitro models to facilitate understanding of CCM pathology and in the future screening for new drugs to treat CCM. ..
  46. Novel Regulators of Bone Formation
    LAURIE HOLLIS GLIMCHER; Fiscal Year: 2012
    ..These new proteins offer exciting targets for the development of anabolics that act at the level of the osteoblast to increase bone mass. ..
  47. The Hydroxylprolylproteome
    Frank S Lee; Fiscal Year: 2013
    ..abstract_text> ..
  48. Enhancing mTOR-targeted cancer therapy
    Shi Yong Sun; Fiscal Year: 2013
    ..The objectives of this proposal are to understand the mechanisms through which raptor and rictor are degraded and to determine the impact of regulation of the degradation of these proteins on mTOR-targeted cancer therapy. ..
  49. Cell-autonomous mechanisms of Ube3a function in the neocortex
    MATTHEW CHARLES JUDSON; Fiscal Year: 2013
    ..Knowledge of these substrates should provide insight into the molecular pathways that are disrupted in Ube3a-deficient neurons and may reveal targets for therapeutic intervention in AS. ..
  50. The Seventh International Mdm2 Workshop
    James J Manfredi; Fiscal Year: 2013
    ..In so doing, duplicate efforts can be avoided, pitfalls can be shared, and knowledge in the field can move forward as rapidly as possible. ..
  51. Regulation of interferon receptor by Leishmania kinase
    SERGE FUCHS; Fiscal Year: 2007
    ....
  52. A PTEN-regulated ubiquitin switch controlling TRAIL sensitivity in GBM
    Russell O Pieper; Fiscal Year: 2010
    ....
  53. Cell Cycle Regulation and Adult T Cell Leukemia
    Chou Zen Giam; Fiscal Year: 2010
    ..The study will provide molecular insights that can lead to the development of treatment strategies for human cancer ..
  54. Cell Cycle Regulation and Adult T Cell Leukemia
    Chou Zen Giam; Fiscal Year: 2011
    ..The study will provide molecular insights that can lead to the development of treatment strategies for human cancer ..
  55. Cell Cycle Regulation and Adult T Cell Leukemia
    Chou Zen Giam; Fiscal Year: 2012
    ..The study will provide molecular insights that can lead to the development of treatment strategies for human cancer ..
  56. Cell Cycle Regulation and Adult T Cell Leukemia
    Chou Zen Giam; Fiscal Year: 2013
    ..The study will provide molecular insights that can lead to the development of treatment strategies for human cancer ..
  57. Role of E3 ubiquitin ligase in Salmonella-induced inflammation
    Daoguo Zhou; Fiscal Year: 2009
    ..My department is committed to a strong research program in this area and has provided an excellent environment to carry out my research goals. ..
  58. Role of E3 ubiquitin ligase in Salmonella-induced inflammation
    Daoguo Zhou; Fiscal Year: 2010
    ..My department is committed to a strong research program in this area and has provided an excellent environment to carry out my research goals. ..
  59. Role of E3 ubiquitin ligase in Salmonella-induced inflammation
    Daoguo Zhou; Fiscal Year: 2007
    ..My department is committed to a strong research program in this area and has provided an excellent environment to carry out my research goals. ..
  60. A PTEN-regulated ubiquitin switch controlling TRAIL sensitivity in GBM
    RUSSELL PIEPER; Fiscal Year: 2009
    ....
  61. HTLV-I Tax activates the anaphase promoting complex
    Chou Zen Giam; Fiscal Year: 2013
    ..The study will provide molecular insights that can lead to the development of treatment strategies for human cancer. ..
  62. HTLV-I Tax activates the anaphase promoting complex
    Chou Zen Giam; Fiscal Year: 2010
    ..The study will provide molecular insights that can lead to the development of treatment strategies for human cancer. ..
  63. Genetic Control of Axial Patterning in Drosophila Eye
    Amit Singh; Fiscal Year: 2010
    ..It will also help to understand the molecular basis of developmental defects caused by mutations in the human homolog of Drosophila. ..
  64. The Role of CRL4-Cdt2 E3 Ubiquitin Ligase in Genomic Stability and Cancer
    TAREK A ABBAS; Fiscal Year: 2010
    ..It will also test the enzymes'role in tumor development. ..
  65. E2 selectivity and activation by CHIP
    SARAH E WARNICK; Fiscal Year: 2010
    ..This work to define specific functional interactions between components of the ubiquitination machinery is a necessary step in monitoring and treating system failures which lead to disease. ..
  66. Induction and maintenance of regulatory T cells
    Mitchell Kronenberg; Fiscal Year: 2013
    ..This proposal will study the mechanisms by which the immune responses are properly controlled. Such knowledge will eventually facilitate the design of novel therapeutic approaches for immunological diseases. ..
  67. Induction and maintenance of regulatory T cells
    Mitchell Kronenberg; Fiscal Year: 2010
    ..This proposal will study the mechanisms by which the immune responses are properly controlled. Such knowledge will eventually facilitate the design of novel therapeutic approaches for immunological diseases. ..
  68. Analysis of BRCA1 E3 Ubiquitin Ligase & Phosphopeptide Binding Activity
    LATARSHA JUANITA REID; Fiscal Year: 2010
    ..These findings could also lead to more specialized treatments and overall improved health care for cancer patients, which supports the mission of the National Cancer Institute. ..
  69. Analysis of BRCA1 E3 Ubiquitin Ligase & Phosphopeptide Binding Activity
    LATARSHA REID; Fiscal Year: 2007
    ..These findings could also lead to more specialized treatments and overall improved health care for cancer patients, which supports the mission of the National Cancer Institute. ..
  70. Analysis of BRCA1 E3 Ubiquitin Ligase & Phosphopeptide Binding Activity
    LATARSHA REID; Fiscal Year: 2009
    ..These findings could also lead to more specialized treatments and overall improved health care for cancer patients, which supports the mission of the National Cancer Institute. ..
  71. E2 selectivity and activation by CHIP
    SARAH SOSS; Fiscal Year: 2009
    ..This work to define specific functional interactions between components of the ubiquitination machinery is a necessary step in monitoring and treating system failures which lead to disease. ..
  72. CYTOSOLIC GLYCOSYLATION
    Christopher West; Fiscal Year: 2003
    ..In addition, the enzyme sequences are expected to be useful for the identification of homologous genes, in the cytoplasm or Golgi, of other 'lower' organisms as their genome sequences are completed. ..
  73. CYTOSOLIC GLYCOSYLATION
    Christopher West; Fiscal Year: 2004
    ..In addition, the enzyme sequences are expected to be useful for the identification of homologous genes, in the cytoplasm or Golgi, of other 'lower' organisms as their genome sequences are completed. ..
  74. CYTOSOLIC GLYCOSYLATION
    Christopher West; Fiscal Year: 2003
    ..In addition, the enzyme sequences are expected to be useful for the identification of homologous genes, in the cytoplasm or Golgi, of other 'lower' organisms as their genome sequences are completed. ..
  75. CYTOSOLIC GLYCOSYLATION
    Christopher West; Fiscal Year: 2002
    ..In addition, the enzyme sequences are expected to be useful for the identification of homologous genes, in the cytoplasm or Golgi, of other 'lower' organisms as their genome sequences are completed. ..
  76. Role of Cul5 E3 ubiquitin ligase in HIV Vif function
    Xiao Fang Yu; Fiscal Year: 2004
    ..This study should provide critical insight into the complex interplay between viral and host factors and may provide us with critical information regarding the design of effective intervention strategies for HIV. ..
  77. Cellular & Inflammatory Pathways in Ashtma & Allergic Diseases: From IgE to Cells
    LAWRENCE BARRY SCHWARTZ; Fiscal Year: 2010
    ....
  78. Cellular & Inflammatory Pathways in Ashtma & Allergic Diseases: From IgE to Cells
    Lawrence Schwartz; Fiscal Year: 2009
    ..Understanding more precisely the characteristics of and the mechanism(s) behind desensitization will enable physicians to better utilize this approach to reduce mast cell/basophil-mediated contributions to asthma and allergic diseases. ..
  79. Cellular & Inflammatory Pathways in Ashtma & Allergic Diseases: From IgE to Cells
    Lawrence Schwartz; Fiscal Year: 2009
    ....
  80. CYTOSOLIC GLYCOSYLATION
    Christopher West; Fiscal Year: 2005
    ..In addition, the enzyme sequences are expected to be useful for the identification of homologous genes, in the cytoplasm or Golgi, of other 'lower' organisms as their genome sequences are completed. ..
  81. Role of Parkin in Regulating Manganese Toxicity
    JEROME ROTH; Fiscal Year: 2009
    ..is not known, our preliminary findings revealed that the gene for early onset of Parkinson's disease, parkin, has the potential to regulate Mn toxicity and, thus for the first time, identify a potential genetic link between ..
  82. Role of Parkin in Regulating Manganese Toxicity
    JEROME ALLAN ROTH; Fiscal Year: 2010
    ..is not known, our preliminary findings revealed that the gene for early onset of Parkinson's disease, parkin, has the potential to regulate Mn toxicity and, thus for the first time, identify a potential genetic link between ..
  83. Trim32 Regulation of Piasy in Skin Homeostasis
    Molly Kulesz Martin; Fiscal Year: 2009
    ..Understanding how Trim32 and Piasy control skin cell survival and skin inflammation promises new ways to treat psoriasis and other human diseases of the skin, as well as inflammatory diseases in other organs of the body. ..
  84. Trim32 Regulation of Piasy in Skin Homeostasis
    Molly F Kulesz Martin; Fiscal Year: 2010
    ..Understanding how Trim32 and Piasy control skin cell survival and skin inflammation promises new ways to treat psoriasis and other human diseases of the skin, as well as inflammatory diseases in other organs of the body. ..
  85. Mechanism of Merlin-mediated contact inhibition and tumor suppression.
    Filippo G Giancotti; Fiscal Year: 2010
    ..It is expected that a mechanistic understanding of Merlin's function will shed light on contact inhibition and on the pathogenesis of NF2 mutant tumors. ..
  86. TRAF6 E3 LIGASE FUNCTION IN OSTEOCLASTOGENESIS
    Bryant Darnay; Fiscal Year: 2009
    ..In particular, the data gathered from these experiments may provide insights to developing therapeutic strategies for a variety of bone related disease and possibly other diseases associated with immunity and inflammation ..
  87. TRAF6 E3 LIGASE FUNCTION IN OSTEOCLASTOGENESIS
    Bryant G Darnay; Fiscal Year: 2010
    ..In particular, the data gathered from these experiments may provide insights to developing therapeutic strategies for a variety of bone related disease and possibly other diseases associated with immunity and inflammation ..
  88. TRAF6 E3 LIGASE FUNCTION IN OSTEOCLASTOGENESIS
    Bryant Darnay; Fiscal Year: 2007
    ..In particular, the data gathered from these experiments may provide insights to developing therapeutic strategies for a variety of bone related disease and possibly other diseases associated with immunity and inflammation ..
  89. Structural Biology of U-box E3 Ubiquitin Ligases
    Walter J Chazin; Fiscal Year: 2010
    ..This information has the potential to open up new therapeutic avenues for treatment of neurodegenerative diseases and certain cancers based on regulating the cellular level of these key molecular chaperones. ..
  90. Structural Biology of U-box E3 Ubiquitin Ligases
    Walter J Chazin; Fiscal Year: 2012
    ..This information has the potential to open up new therapeutic avenues for treatment of neurodegenerative diseases and certain cancers based on regulating the cellular level of these key molecular chaperones. ..
  91. Novel Mechanisms by which RAD18 and POLZ affect Response to Anticancer Agents
    CHRISTINE ELIZABETH CANMAN; Fiscal Year: 2010
    ....
  92. Novel Mechanisms by which RAD18 and POLZ affect Response to Anticancer Agents
    CHRISTINE CANMAN; Fiscal Year: 2009
    ....
  93. REGULATION OF DEFENSE SIGNALING IN TOMATO
    Gregg A Howe; Fiscal Year: 2010
    ....
  94. REGULATION OF DEFENSE SIGNALING IN TOMATO
    Gregg Howe; Fiscal Year: 2009
    ....
  95. REGULATION OF DEFENSE SIGNALING IN TOMATO
    Gregg A Howe; Fiscal Year: 2010
    ....
  96. Salmonella SopA is a functional mimicry of eukaryotic E3 protein ubiquitin ligase
    Daoguo Zhou; Fiscal Year: 2009
    ..Results from this study will help us understand how Salmonella induces intestinal inflammation in humans. ..
  97. Salmonella SopA is a functional mimicry of eukaryotic E3 protein ubiquitin ligase
    Daoguo Zhou; Fiscal Year: 2010
    ..Results from this study will help us understand how Salmonella induces intestinal inflammation in humans. ..
  98. FUNCTION OF INK4A/ARF IN PEDIATRIC NEOPLASIA
    Martine Roussel; Fiscal Year: 2001
    ..abstract_text> ..
  99. Vpr Revisited
    NATHANIEL LANDAU; Fiscal Year: 2009
    ..The project will determine how this happens and how it affects replication of HIV. ..
  100. Novel Small Molecule Inhibitors of HIV
    Xiao Fang Yu; Fiscal Year: 2009
    ..We have identified a small molecule inhibitor of Vif. The overall goal of this project is to further characterize the novel small molecule Vif inhibitor and its derivatives that restore the potent innate antiviral defense. ..
  101. Novel Small Molecule Inhibitors of HIV
    Xiao Fang Yu; Fiscal Year: 2010
    ..We have identified a small molecule inhibitor of Vif. The overall goal of this project is to further characterize the novel small molecule Vif inhibitor and its derivatives that restore the potent innate antiviral defense. ..