Parkin

Summary

Gene Symbol: Parkin
Description: parkin RBR E3 ubiquitin protein ligase
Alias: AR-JP, LPRS2, PDJ, PRKN, 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. 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
  3. 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
  4. pmc Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization
    Shireen A Sarraf
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nature 496:372-6. 2013
  5. pmc PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility
    Xinnan Wang
    F M Kirby Neurobiology Center, Children s Hospital Boston, Boston, MA 02115, USA
    Cell 147:893-906. 2011
  6. pmc PINK1-dependent recruitment of Parkin to mitochondria in mitophagy
    Cristofol Vives-Bauza
    Department of Neurology, Columbia University, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 107:378-83. 2010
  7. 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
  8. 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
  9. pmc PARIS (ZNF746) repression of PGC-1α contributes to neurodegeneration in Parkinson's disease
    Joo Ho Shin
    Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Cell 144:689-702. 2011
  10. pmc PINK1-mediated phosphorylation of the Parkin ubiquitin-like domain primes mitochondrial translocation of Parkin and regulates mitophagy
    Kahori Shiba-Fukushima
    Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo 113 8421, Japan
    Sci Rep 2:1002. 2012

Detail Information

Publications279 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. 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...
  3. 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...
  4. pmc Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization
    Shireen A Sarraf
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nature 496:372-6. 2013
    The PARKIN ubiquitin ligase (also known as PARK2) and its regulatory kinase PINK1 (also known as PARK6), often mutated in familial early-onset Parkinson's disease, have central roles in mitochondrial homeostasis and mitophagy...
  5. pmc PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility
    Xinnan Wang
    F M Kirby Neurobiology Center, Children s Hospital Boston, Boston, MA 02115, USA
    Cell 147:893-906. 2011
    ..We report here that two Parkinson's disease proteins, the Ser/Thr kinase PINK1 and ubiquitin ligase Parkin, participate in this regulation by arresting mitochondrial movement...
  6. pmc PINK1-dependent recruitment of Parkin to mitochondria in mitophagy
    Cristofol Vives-Bauza
    Department of Neurology, Columbia University, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 107:378-83. 2010
    Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1) and PARK2/Parkin mutations cause autosomal recessive forms of Parkinson's disease...
  7. 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)...
  8. 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 ..
  9. pmc PARIS (ZNF746) repression of PGC-1α contributes to neurodegeneration in Parkinson's disease
    Joo Ho Shin
    Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Cell 144:689-702. 2011
    ..Here, we identify a new parkin interacting substrate, PARIS (ZNF746), whose levels are regulated by the ubiquitin proteasome system via binding ..
  10. pmc PINK1-mediated phosphorylation of the Parkin ubiquitin-like domain primes mitochondrial translocation of Parkin and regulates mitophagy
    Kahori Shiba-Fukushima
    Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo 113 8421, Japan
    Sci Rep 2:1002. 2012
    Parkinson's disease genes PINK1 and parkin encode kinase and ubiquitin ligase, respectively. The gene products PINK1 and Parkin are implicated in mitochondrial autophagy, or mitophagy...
  11. 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...
  12. pmc Parkin mitochondrial translocation is achieved through a novel catalytic activity coupled mechanism
    Xinde Zheng
    Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
    Cell Res 23:886-97. 2013
    Pink1, a mitochondrial kinase, and Parkin, an E3 ubiquitin ligase, function in mitochondrial maintenance...
  13. pmc PINK1 drives Parkin self-association and HECT-like E3 activity upstream of mitochondrial binding
    Michael Lazarou
    Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 200:163-72. 2013
    Genetic studies indicate that the mitochondrial kinase PINK1 and the RING-between-RING E3 ubiquitin ligase Parkin function in the same pathway...
  14. pmc Structure of the human Parkin ligase domain in an autoinhibited state
    Tobias Wauer
    Division of Protein and Nucleic Acid Chemistry, Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
    EMBO J 32:2099-112. 2013
    Mutations in the protein Parkin are associated with Parkinson's disease (PD), the second most common neurodegenerative disease in men...
  15. 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...
  16. 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...
  17. 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 ..
  18. 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...
  19. 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...
  20. 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)...
  21. pmc Structure and function of Parkin E3 ubiquitin ligase reveals aspects of RING and HECT ligases
    B E Riley
    Elan Pharmaceuticals, 180 Oyster Point Boulevard, South San Francisco, California 94080, USA
    Nat Commun 4:1982. 2013
    b>Parkin is a RING-between-RING E3 ligase that functions in the covalent attachment of ubiquitin to specific substrates, and mutations in Parkin are linked to Parkinson's disease, cancer and mycobacterial infection...
  22. 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...
  23. 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...
  24. pmc Mitochondrial processing peptidase regulates PINK1 processing, import and Parkin recruitment
    Andrew W Greene
    McGill Parkinson Program, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada
    EMBO Rep 13:378-85. 2012
    ..depolarization, PINK1 accumulates on the mitochondrial surface where it recruits the PD-linked E3 ubiquitin ligase Parkin from the cytosol, which in turn mediates the autophagic destruction of the dysfunctional organelles...
  25. doi The E3 ligase parkin maintains mitochondrial integrity by increasing linear ubiquitination of NEMO
    Anne Kathrin Müller-Rischart
    Neurobiochemistry, Adolf Butenandt Institute, Ludwig Maximilians University, 80336 Munich, Germany
    Mol Cell 49:908-21. 2013
    b>Parkin, a RING-between-RING-type E3 ubiquitin ligase associated with Parkinson's disease, has a wide neuroprotective activity, preventing cell death in various stress paradigms...
  26. 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'.
  27. 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...
  28. 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 ..
  29. 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...
  30. 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...
  31. doi Differential expression of alpha-synuclein, parkin, and synphilin-1 isoforms in Lewy body disease
    Katrin Beyer
    Department of Pathology, Hospital Germans Trias i Pujol, Autonomous University of Barcelona, Barcelona, Spain
    Neurogenetics 9:163-72. 2008
    Alpha-synuclein, parkin, and synphilin-1 are proteins mainly involved in the pathogenesis of Lewy body (LB) diseases. mRNAs of all three undergo alternative splicing, so that the existence of various isoforms has been described...
  32. 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...
  33. doi 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)...
  34. 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...
  35. 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...
  36. 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.
  37. doi Parkin promotes the ubiquitination and degradation of the mitochondrial fusion factor mitofusin 1
    Liliane Glauser
    Laboratory of Molecular Neurodegenerative Research, Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Federale de Lausanne EPFL, Lausanne, Switzerland
    J Neurochem 118:636-45. 2011
    Mutations in the parkin gene cause early-onset, autosomal recessive Parkinson's disease. Parkin functions as an E3 ubiquitin ligase to mediate the covalent attachment of ubiquitin monomers or linked chains to protein substrates...
  38. 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 ..
  39. 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...
  40. 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...
  41. pmc Parkin ubiquitinates Drp1 for proteasome-dependent degradation: implication of dysregulated mitochondrial dynamics in Parkinson disease
    Hongxia Wang
    Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, Tianjin, China
    J Biol Chem 286:11649-58. 2011
    Mutations in Parkin, an E3 ubiquitin ligase that regulates protein turnover, represent one of the major causes of familial Parkinson disease, a neurodegenerative disorder characterized by the loss of dopaminergic neurons and impaired ..
  42. pmc A molecular explanation for the recessive nature of parkin-linked Parkinson's disease
    Donald E Spratt
    Department of Biochemistry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada N6A 5C1
    Nat Commun 4:1983. 2013
    Mutations in the park2 gene, encoding the RING-inBetweenRING-RING E3 ubiquitin ligase parkin, cause 50% of autosomal recessive juvenile Parkinsonism cases...
  43. 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...
  44. pmc Phosphorylation of Parkin at Serine65 is essential for activation: elaboration of a Miro1 substrate-based assay of Parkin E3 ligase activity
    Agne Kazlauskaite
    MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UK
    Open Biol 4:130213. 2014
    Mutations in PINK1 and Parkin are associated with early-onset Parkinson's disease...
  45. 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 ..
  46. doi ER-stress-associated functional link between Parkin and DJ-1 via a transcriptional cascade involving the tumor suppressor p53 and the spliced X-box binding protein XBP-1
    Eric Duplan
    Institut de Pharmacologie Moleculaire et Cellulaire, UMR7275 CNRS UNSA, Team Fondation pour la Recherche Médicale and Labex Distalz, 660 route des Lucioles, 06560, Sophia Antipolis, Valbonne, France
    J Cell Sci 126:2124-33. 2013
    b>Parkin and DJ-1 are two multi-functional proteins linked to autosomal recessive early-onset Parkinson's disease (PD) that have been shown to functionally interact by as-yet-unknown mechanisms...
  47. pmc Lysine 27 ubiquitination of the mitochondrial transport protein Miro is dependent on serine 65 of the Parkin ubiquitin ligase
    Nicol Birsa
    From the Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, United Kingdom
    J Biol Chem 289:14569-82. 2014
    ..protein crucial for the regulation of mitochondrial trafficking and distribution, is a substrate of the PINK1/Parkin mitochondrial quality control system in human dopaminergic neuroblastoma cells...
  48. pmc Structure and Function of Parkin, PINK1, and DJ-1, the Three Musketeers of Neuroprotection
    Jean Francois Trempe
    McGill Parkinson Program, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University Montreal, QC, Canada
    Front Neurol 4:38. 2013
    Autosomal recessive forms of Parkinson's disease are caused by mutations in three genes: Parkin, PINK1, and DJ-1. These genes encode for proteins with distinct enzymatic activities that may work together to confer neuroprotection...
  49. 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...
  50. 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...
  51. pmc Parkin promotes degradation of the mitochondrial pro-apoptotic ARTS protein
    Stav Kemeny
    Cell Death Research Laboratory, Department of Biology, Faculty of Sciences, University of Haifa, Mount Carmel, Haifa, Israel
    PLoS ONE 7:e38837. 2012
    ..Dysfunction of the Ubiquitin Proteasome System (UPS) is associated with the pathophysiology of PD. Mutations in Parkin which impair its E3-ligase activity play a major role in the pathogenesis of inherited PD...
  52. 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)...
  53. 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...
  54. pmc Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1)-dependent ubiquitination of endogenous Parkin attenuates mitophagy: study in human primary fibroblasts and induced pluripotent stem cell-derived neurons
    Aleksandar Rakovic
    Section of Clinical and Molecular Neurogenetics at the Department of Neurology, University of Lubeck, 23562 Lübeck, Germany
    J Biol Chem 288:2223-37. 2013
    Mutations in the E3 ubiquitin ligase Parkin and the mitochondrial PTEN-induced putative kinase 1 (PINK1) have been identified to cause autosomal recessive forms of familial Parkinson disease, with PINK1 functioning upstream of Parkin in a ..
  55. 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...
  56. 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...
  57. 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)...
  58. 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 ..
  59. pmc Somatic mutations of the Parkinson's disease-associated gene PARK2 in glioblastoma and other human malignancies
    Selvaraju Veeriah
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA
    Nat Genet 42:77-82. 2010
    ..These data strongly point to PARK2 as a tumor suppressor on 6q25.2-q27. Thus, PARK2, a gene that causes neuronal dysfunction when mutated in the germline, may instead contribute to oncogenesis when altered in non-neuronal somatic cells...
  60. ncbi The PINK1/Parkin-mediated mitophagy is compromised by PD-associated mutations
    Sven Geisler
    Laboratory of Functional Neurogenetics, Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tubingen, and German Centre for Neurodegenerative Diseases, Tubingen, Germany
    Autophagy 6:871-8. 2010
    ..Very recently, two Parkinson disease (PD) associated genes, PINK1 and Parkin, were shown to mediate the degradation of damaged mitochondria via selective autophagy (mitophagy)...
  61. 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...
  62. pmc Parkin binds to alpha/beta tubulin and increases their ubiquitination and degradation
    Yong Ren
    Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, New York 14214, USA
    J Neurosci 23:3316-24. 2003
    ..Here we report that parkin, a protein-ubiquitin E3 ligase linked to PD, was tightly bound to microtubules in taxol-mediated microtubule ..
  63. 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...
  64. pmc Inactivation of Pink1 gene in vivo sensitizes dopamine-producing neurons to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and can be rescued by autosomal recessive Parkinson disease genes, Parkin or DJ-1
    M Emdadul Haque
    Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada
    J Biol Chem 287:23162-70. 2012
    ..Importantly, we also show that viral mediated expression of two other recessive PD-linked familial genes, DJ-1 and Parkin, can protect dopaminergic neurons even in the absence of Pink1...
  65. doi Systematic review and UK-based study of PARK2 (parkin), PINK1, PARK7 (DJ-1) and LRRK2 in early-onset Parkinson's disease
    Laura L Kilarski
    MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Neurology, School of Medicine, Cardiff University, Cardiff, United Kingdom
    Mov Disord 27:1522-9. 2012
    ..from a high-ascertainment regional and community-based prevalence study for pathogenic mutations in PARK2 (parkin), PINK1, PARK7 (DJ-1), and exon 41 of LRRK2...
  66. pmc Ataxin-3 deubiquitination is coupled to Parkin ubiquitination via E2 ubiquitin-conjugating enzyme
    Thomas M Durcan
    Department of Neurology and Neurosurgery, Centre for Neuronal Survival and McGill Parkinson Program, Montreal Neurological Institute, Montreal, Quebec, Canada
    J Biol Chem 287:531-41. 2012
    We reported previously that parkin, a Parkinson disease-associated E3 ubiquitin-ligase interacts with ataxin-3, a deubiquitinating enzyme associated with Machado-Joseph disease...
  67. doi Molecular interaction between parkin and PINK1 in mammalian neuronal cells
    Ji Won Um
    Department of Biology, College of Life Science and Biotechnology, Yonsei University, 262 Seongsanno, Seodaemun gu, Seoul 120 749, Republic of Korea
    Mol Cell Neurosci 40:421-32. 2009
    ..Mutations in PTEN-induced putative kinase 1 (PINK1) and parkin are linked to early-onset autosomal recessive forms of familial PD...
  68. ncbi Co-association of parkin and alpha-synuclein
    P Choi
    Department of Pharmacology, Loyola University Medical Center, Bldg 102, Rm 3634, 2160 S 1st Ave, Maywood, IL 60153, USA
    Neuroreport 12:2839-43. 2001
    b>Parkin and alpha-synuclein are two proteins that are associated with the pathophysiology of Parkinson's disease (PD)...
  69. ncbi The p38 subunit of the aminoacyl-tRNA synthetase complex is a Parkin substrate: linking protein biosynthesis and neurodegeneration
    Olga Corti
    INSERM U289, Hopital de la Salpetriere, Bâtiment Pharmacie, 47 Boulevard de l Hopital, 75651 Paris Cedex 13, France
    Hum Mol Genet 12:1427-37. 2003
    ..Mutations in the parkin gene, which encodes an E3 ubiquitin-protein ligase involved in the ubiquitylation and proteasomal degradation of ..
  70. 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...
  71. doi 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...
  72. 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...
  73. 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...
  74. 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...
  75. 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...
  76. doi 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...
  77. 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...
  78. 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...
  79. 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...
  80. 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)...
  81. ncbi Parkin and CASK/LIN-2 associate via a PDZ-mediated interaction and are co-localized in lipid rafts and postsynaptic densities in brain
    Lara Fallon
    Centre for Neuronal Survival, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada
    J Biol Chem 277:486-91. 2002
    Mutations in the gene encoding parkin cause an autosomal recessive juvenile-onset form of Parkinson's disease...
  82. 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...
  83. 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.
  84. 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)...
  85. 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...
  86. 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...
  87. 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...
  88. 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...
  89. 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...
  90. 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...
  91. 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).
  92. doi 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.
  93. 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 ..
  94. 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...
  95. ncbi Parkin mutations and susceptibility alleles in late-onset Parkinson's disease
    Sofia A Oliveira
    Department of Medicine and Center for Human Genetics, Institute for Genome Sciences and Policy, Duke University Medical Center, Durham, NC 27710, USA
    Ann Neurol 53:624-9. 2003
    b>Parkin, an E2-dependent ubiquitin protein ligase, carries pathogenic mutations in patients with autosomal recessive juvenile parkinsonism, but its role in the late-onset form of Parkinson's disease (PD) is not firmly established...
  96. 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 ..
  97. pmc Disease-causing mutations in parkin impair mitochondrial ubiquitination, aggregation, and HDAC6-dependent mitophagy
    Joo Yong Lee
    Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA
    J Cell Biol 189:671-9. 2010
    Mutations in parkin, a ubiquitin ligase, cause early-onset familial Parkinson's disease (AR-JP). How parkin suppresses parkinsonism remains unknown...
  98. ncbi Parkin mediates neuroprotection through activation of IkappaB kinase/nuclear factor-kappaB signaling
    Iris H Henn
    Department of Biochemistry, Adolf Butenandt Institute, D 80336 Munich, Germany
    J Neurosci 27:1868-78. 2007
    Mutations in the parkin gene are a major cause of autosomal recessive Parkinson's disease. Here we show that the E3 ubiquitin ligase parkin activates signaling through the IkappaB kinase (IKK)/nuclear factor kappaB (NF-kappaB) pathway...
  99. ncbi An unfolded putative transmembrane polypeptide, which can lead to endoplasmic reticulum stress, is a substrate of Parkin
    Y Imai
    Laboratory for Motor System Neurodegeneration, RIKEN Brain Science Institute, Saitama 351 0198, Japan
    Cell 105:891-902. 2001
    ..G protein-coupled transmembrane polypeptide, named Pael receptor, was identified as an interacting protein with Parkin, a gene product responsible for autosomal recessive juvenile Parkinsonism (AR-JP)...
  100. 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...
  101. 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...

Research Grants105 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. 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. ..
  3. Inflammatory Proteases, Ubiquitin Proteasome System, and Myocyte Death
    Abdelkarim Sabri; Fiscal Year: 2012
    ....
  4. Study of an iron-responsive E3 ligase regulating mammalian iron homeostasis
    Richard K Bruick; Fiscal Year: 2013
    ..To that end, this proposal describes the characterization of a candidate sensor and regulator of mammalian iron homeostasis, FBXL5. ..
  5. REGULATION OF DEFENSE SIGNALING IN TOMATO
    Gregg A Howe; Fiscal Year: 2012
    ....
  6. 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. ..
  7. Structural Biology of U-box E3 Ubiquitin Ligases
    Walter J Chazin; Fiscal Year: 2013
    ..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. ..
  8. SUMO-dependent Regulation of Ubiquitin Ligases in Genomic Stability
    Michael N Boddy; Fiscal Year: 2012
    ..Additionally, a detailed understanding of STUbL function should yield general implications for responses to genotoxic stress. ..
  9. Partitioning of Misfolded Membrane Proteins Between Different Degradatory Fates
    SCOTT ANDREW HOUCK; Fiscal Year: 2013
    ..The results obtained here will greatly further our knowledge of how the cell recognizes defects in transmembrane spans and the mechanisms by which those proteins are degraded. ..
  10. Nedd4-family ubiquitination networks that regulate T cell function
    PAULA MARIA OLIVER; Fiscal Year: 2012
    ..These studies have the potential to identify novel therapeutic targets for regulating the immune response, and might provide new treatments options to clinically manage autoimmune and inflammatory diseases. ..
  11. Mechanisms of protein degradation and transcriptional regulation by ubiquitin mod
    Christopher Hickey; Fiscal Year: 2013
    ..Since many transcriptional regulators and other DNA-binding proteins are known to be ubiquitinated, this project is likely to have implications beyond the ?2 system. ..
  12. Regulators and mediators of TRIM5 function
    Jacek Skowronski; Fiscal Year: 2010
    ..Knowledge gained from our studies could lead to the conception of new strategies to control HIV infection and to the identification of new targets for development of anti-retroviral drugs. ..
  13. Mechanism of Gli3 processing in Hedgehog signaling
    Baolin Wang; Fiscal Year: 2013
    ..The completion of the proposed studies will significantly advance our understanding of the regulation and function of Gli3 protein in Hh signaling. ..
  14. CARP-1: A Potential Therapeutic Agent for Breast Cancer
    ARUN KUMAR RISHI; Fiscal Year: 2013
    ..abstract_text> ..
  15. Small Molecule Inhibitors of Mdm2 E3 Ubiquitin Ligase Activity for Cancer Therapy
    Claudio A P Joazeiro; Fiscal Year: 2013
    ..The discovery of inhibitors of Mdm2 E3 ligase activity with anti-tumor properties will thus represent a significant innovation in the development of drugs for the treatment of cancer. ..
  16. STEROID CONTROL OF EPITHELIAL CELL-CELL INTERACTIONS
    Gary L Firestone; Fiscal Year: 2011
    ..A final goal is to functionally characterize the roles of GSK3 and CAS and their degradative systems in the steroid dependent control of beta-catenin dynamics, apical junction organization and tight junction formation. ..
  17. Studies on ROC1-dependent E3 Ubiquitin Ligases
    Zhen Qiang Pan; Fiscal Year: 2013
    ....
  18. Role of Natural Killer Lytic-Associated Molecule (NKLAM) in Natural Killer Functi
    Jacki Kornbluth; Fiscal Year: 2010
    ..These diseases are of great relevance to the health care system as the incidence of cancer is rising as the population is aging and new, resistant microbial pathogens are emerging and spreading. ..
  19. Cellular &Inflammatory Pathways in Ashtma &Allergic Diseases: From IgE to Cells
    LAWRENCE BARRY SCHWARTZ; Fiscal Year: 2012
    ..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. ..
  20. REGULATION AND FUNCTION OF STE20-RELATED PROTEIN KINASES
    Melanie H Cobb; Fiscal Year: 2012
    ..Understanding the mechanisms of action of this family will provide significant insights into the control of ion balance and other essential processes, and may reveal novel strategies to develop anti-hypertensive therapies. ..
  21. CONTROL OF APOPTOSIS BY DROSOPHILA CELL DEATH GENES
    Hermann Steller; Fiscal Year: 2012
    ..Therefore, this project will have profound implications for both basic science and medicine. ..
  22. Programmed Cell Death and Disease Resistance in Arabidopsis
    Roger W Innes; Fiscal Year: 2013
    ..Together with Specific Aims 1-3, these analyses will provide significant new insight into how PCD and immunity are regulated. ..
  23. Epithelial Sodium Channel Trafficking
    Peter M Snyder; Fiscal Year: 2013
    ..This may have important implications for our understanding and treatment of diseases including hypertension and cystic fibrosis. ..
  24. Role of SAG/RBX2 E3 Ubiquitin Ligase in Skin Carcinogenesis
    Yi Sun; Fiscal Year: 2013
    ....
  25. Proteolytic silencing of cancer targets using engineered ubiquitin ligases
    Matthew P DeLisa; Fiscal Year: 2013
    ....
  26. Structural studies of cullin-based ubiquitin ligases
    Ning Zheng; Fiscal Year: 2013
    ....
  27. Role of Parkinson's disease gene PARK2 in GBM oncogenesis and genomic instability
    TIMOTHY AN THY CHAN; Fiscal Year: 2013
    ..abstract_text> ..
  28. Function and Mechanism of CUL4 E3 Ligases in Human Diseases
    Yue Xiong; Fiscal Year: 2013
    ..Finally, we propose to determine broadly the function of CUL4B in the regulation of chromatin modification and gene expression. ..
  29. Signaling functions of Peli family of E3 ubiquitin ligases
    Shao Cong Sun; Fiscal Year: 2013
    ....
  30. 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. ..
  31. E3 Ubiquitin Ligase Functions in Enveloped Virus Budding
    ANDREW PAUL NORGAN; Fiscal Year: 2012
    ..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. ..
  32. Alteration of host protein stability by Legionella
    Michael N Starnbach; Fiscal Year: 2012
    ..The experiments described in this proposal allow, for the first time, dissection of how bacterial infection globally regulates host cell proteins and pathways beyond the transcriptional level. ..
  33. NOVEL REGULATORS OF LATE STAGE BONE MARROW ERYTHROBLAST DEVELOPMENT
    Don Wojchowski; Fiscal Year: 2012
    ..Proposed work promises to discover and characterize novel regulators of erythroblast and RBC production as potentially drugable E3 ligase complexes;and as a new RBC progenitor niche in bone marrow with unique expansion potential. ..
  34. MODULATION OF NF-kB ACTIVATION BY A NOVEL MITOCHONDRIAL E3 UBIQUITIN LIGASE
    Claudio A P Joazeiro; Fiscal Year: 2012
    ..Small molecules targeting the pathway are in clinical development. The results of the proposed studies should ultimately translate into the identification of new targets for drug discovery. ..
  35. Quantitative Analysis of RING E3 Ubiquitin Ligases
    CHARLES M BRENNER; Fiscal Year: 2010
    ..Second, innovations in analysis of RING E3 ubiquitin ligases are necessary to understand the specificity of function of RING E3 ubiquitin ligases, which have key functions in the health of every organ system. ..
  36. E3 Ligases and Deubiquitinases in GPCR Down Regulation
    Sudha K Shenoy; Fiscal Year: 2013
    ..The long-term goal of this project is to understand the molecular mechanisms that integrate G protein-coupled receptor trafficking and signaling, which could play a critical role in balancing physiological responsiveness. ..
  37. Regulation of Osteoblast Function by Megakaryocytes: Key Signaling Proteins
    Melissa A Kacena; Fiscal Year: 2013
    ..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. ..
  38. Structural and biochemical studies of protein PARylation and PARylation-dependent
    Wenqing Xu; Fiscal Year: 2013
    ..The availability of specific PARG inhibitors will have a significant impact on efforts to explore the biological role of protein PARylation in addition to their potential therapeutic value. ..
  39. Biology of nuclear receptor rev-erb alpha in circadian rhythm and metabolism
    Lei Yin; Fiscal Year: 2009
    ..In addition, this work may shed the new light on identifying new therapeutic targets for treating insulin resistance and diabetes. ..
  40. Biology of nuclear receptor rev-erb alpha in circadian rhythm and metabolism
    Lei Yin; Fiscal Year: 2011
    ..In addition, this work may shed the new light on Identifying the new therapeutic targets for treating Insulin resistance and diabetes. ..
  41. Regulation of SMN and Identification of its Downstream Target
    Judith Jebanathirajah Steen; Fiscal Year: 2013
    ..abstract_text> ..
  42. Ubiquitin-like protein modification in diabetic cardiomyopathy
    Jay Yang; Fiscal Year: 2013
    ..The significance lies in the novel hypothesis on the role of the Ub-ligase CHIP in regulating both apoptosis and autophagy, and the proposed mechanistic study of a highly clinically relevant problem. ..
  43. 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. ..
  44. Indolecarbinol target proteins and anti-cancer signaling in human melanoma cells
    Gary L Firestone; Fiscal Year: 2013
    ..Our proposed studies will establish the preclinical foundation that is needed to eventually develop novel and low cost I3C-based therapeutic strategies for human skin cancers. ..
  45. A Novel Carcinogen-Induced Cell Cycle Checkpoint
    Cyrus Vaziri; Fiscal Year: 2013
    ..g. Rad18 or its activating kinases) whose inhibition enhances the efficacy of existing cancer therapies. ..
  46. L2DTL Function in Maintaining Genomic Stability during Drosophila Development
    CATHERINE SILVER KEY; Fiscal Year: 2010
    ..Experiment results should support the hypothesis that L2DTL is essential for preventing re-replication in all cell contexts. ..
  47. Ubr1: A Protein Quality Control E3 Ubiquitin Ligase
    Randolph Y Hampton; Fiscal Year: 2013
    ..Our studies will define those functions and eventually the ways to harness or quell them for basic and biomedical benefit. ..
  48. 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 ..
  49. The function and regulation of the cullin family E3 ubiquitin ligases
    Zhen Qiang Pan; Fiscal Year: 2012
    ....
  50. Mechanisms and Relevance of Sodium Transport Regulation by AMPK
    Kenneth R Hallows; Fiscal Year: 2013
    ....
  51. Dynamic regulation of salicylic acid biosynthesis &perception in plant immunity
    Xinnian Dong; Fiscal Year: 2013
    ....
  52. 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. ..
  53. Posttranslational processing of tau: function & dysfunc.
    Gail Johnson; Fiscal Year: 2009
    ..abstract_text> ..
  54. Cellular Stress Response Signaling Pathways
    MICHAEL BARRY KASTAN; Fiscal Year: 2013
    ....
  55. Controlling VSMC Proliferation and Migration
    Ming Hui Zou; Fiscal Year: 2013
    ....
  56. Mechanism, regulation and function of PP2A ubiquitination
    Brian E Wadzinski; Fiscal Year: 2010
    ..abstract_text> ..
  57. Parvovirus-Cell Interactions
    David J Pintel; Fiscal Year: 2013
    ..Studies in this last area should also shed light on basic differences between the autonomous and helper-requiring groups of parvoviruses, and also help improve recombinant AAV vector production. ..
  58. Tegument ICP0 and HSV Entry
    Anthony V Nicola; Fiscal Year: 2010
    ..Greater understanding of the virus entry process may help to develop novel approaches to prevent herpes infections. ..
  59. Differential regulation of cardiomyocyte survival and hypertrophy
    Peter Erhardt; Fiscal Year: 2010
    ..Therefore, functional analysis of the Mdm2/Mdm4 system in the heart would contribute to the development of efficient and safe drugs or treatment protocols that have minimal cardiotoxic side effects. ..
  60. Parkin protection in gene transfer animal models (KO-1 Award)
    Charbel Moussa; Fiscal Year: 2012
    ..b>Parkin is an E3 ubiquitin-ligase involved in the proteasomal degradation of misfolded proteins...
  61. Inflammatory Proteases and Diabetic Cardiomyopathy
    Khadija Rafiq; Fiscal Year: 2013
    ....
  62. Osteopontin regulates ubiquitin-proteasome degradation of STAT1
    Paul C Kuo; Fiscal Year: 2012
    ..Characterization of this regulatory pathway may identify potential regulatory targets for therapy in septic shock. ..
  63. Coordinated regulation of MAP kinase signaling by ubiquitination
    JILLIAN HEYWARD HURST; Fiscal Year: 2012
    ..This proposal aims to identify a new mechanism that regulates cellular signaling and possibly reveal new ways to modulate signaling pathways to combat disease. ..
  64. The role of the SCF/FBW7 ubiquitin ligase complex in hematopiesis and leukemia
    Iannis Aifantis; Fiscal Year: 2013
    ..Finally, we study both in vitro and in vivo the effect of Fbw7 mutations on gamma-secretase inhibitor treatment of T-ALL. ..
  65. Spinocerebellar Ataxia Type 2 Gene and Gene Product
    Stefan M Pulst; Fiscal Year: 2012
    ..In the previous funding period we defined the calcium channel subunit CACNA1A (Cav2.1) and the parkin E3 ubiquitin ligase as modifiers of the SCA2 phenotype in vitro and in humans...
  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. Substrates and Binding Partners in the PINK1/Parkin Pathway
    Derek P Narendra; Fiscal Year: 2011
    ..Loss of function mutations in PINK1 and Parkin cause familial parkinsonism (3, 4)...
  68. 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 ..
  69. 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. ..
  70. 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. ..
  71. 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. ..
  72. Hypoxia and Anticancer Drug Action
    Garth Powis; Fiscal Year: 2013
    ..abstract_text> ..
  73. 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. ..
  74. The role of MID1/MID2 in regulating epithelial adhesion
    CATHERINE KOTO; Fiscal Year: 2013
    ....
  75. 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. ..
  76. Histone chaperones and epigenetic silencing
    Zhiguo Zhang; Fiscal Year: 2013
    ....
  77. 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. ..
  78. 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. ..
  79. 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. ..
  80. 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. ..
  81. Identification of the protein homeostasis network that controls the quality contr
    CHRISTINE MARIE LIVINGSTON; Fiscal Year: 2013
    ....
  82. Molecular control of spermatogonial stem cell fate for achieving cell therapy
    Christina Tenenhaus Dann; Fiscal Year: 2013
    ....
  83. 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. ..
  84. 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. ..
  85. 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. ..
  86. Cytochrome c Degradation: A Mechanism to Restrict Apoptosis in Postmitotic Cells
    Mohanish Deshmukh; Fiscal Year: 2013
    ....
  87. The Role of ATF3 in the DNA Damage Response
    Chunhong Yan; Fiscal Year: 2013
    ....
  88. BubRI in Cancer and Aging
    Jan M van Deursen; Fiscal Year: 2013
    ....
  89. Regulation of hematopoietic stem cell maintenance and survival by NKAP
    Virginia Smith Shapiro; Fiscal Year: 2013
    ....
  90. 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. ..
  91. 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. ..
  92. The Hydroxylprolylproteome
    Frank S Lee; Fiscal Year: 2013
    ..abstract_text> ..
  93. 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. ..
  94. 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. ..
  95. 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. ..
  96. 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. ..
  97. 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. ..
  98. 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. ..
  99. 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 ..
  100. 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 ..
  101. 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. ..