Genomes and Genes
Gene Symbol: Parkin
Description: parkin RBR E3 ubiquitin protein ligase
Alias: AR-JP, LPRS2, PARK2, PDJ, E3 ubiquitin-protein ligase parkin, Parkinson disease (autosomal recessive, juvenile) 2, parkin, parkinson juvenile disease protein 2, parkinson protein 2 E3 ubiquitin protein ligase, parkinson protein 2, E3 ubiquitin protein ligase (parkin)
Publications311 found, 100 shown here
- Parkin is recruited selectively to impaired mitochondria and promotes their autophagyDerek 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. 2008Loss-of-function mutations in Park2, the gene coding for the ubiquitin ligase Parkin, are a significant cause of early onset Parkinson's disease...
- PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1Sven Geisler
Laboratory of Functional Neurogenetics, Otfried Muller Strasse 27, 72076 Tubingen, Germany
Nat Cell Biol 12:119-31. 2010Parkinson'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...
- Broad activation of the ubiquitin-proteasome system by Parkin is critical for mitophagyNickie C Chan
Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
Hum Mol Genet 20:1726-37. 2011b>Parkin, an E3 ubiquitin ligase implicated in Parkinson's disease, promotes degradation of dysfunctional mitochondria by autophagy...
- Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarizationShireen A Sarraf
Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
Nature 496:372-6. 2013The 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...
- PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motilityXinnan 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...
- PINK1-dependent recruitment of Parkin to mitochondria in mitophagyCristofol Vives-Bauza
Department of Neurology, Columbia University, New York, NY 10032, USA
Proc Natl Acad Sci U S A 107:378-83. 2010Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1) and PARK2/Parkin mutations cause autosomal recessive forms of Parkinson's disease...
- PARIS (ZNF746) repression of PGC-1α contributes to neurodegeneration in Parkinson's diseaseJoo 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 ..
- PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase activityLesley A Kane
Biochemistry Section, Surgical Neurology Branch, and 2 Protein Peptide Sequencing Facility, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20824
J Cell Biol 205:143-53. 2014PINK1 kinase activates the E3 ubiquitin ligase Parkin to induce selective autophagy of damaged mitochondria. However, it has been unclear how PINK1 activates and recruits Parkin to mitochondria...
- PINK1-mediated phosphorylation of the Parkin ubiquitin-like domain primes mitochondrial translocation of Parkin and regulates mitophagyKahori Shiba-Fukushima
Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo 113 8421, Japan
Sci Rep 2:1002. 2012Parkinson'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...
- Loss-of-function of human PINK1 results in mitochondrial pathology and can be rescued by parkinNicole 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...
- Parkin is activated by PINK1-dependent phosphorylation of ubiquitin at Ser65Agne Kazlauskaite
MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, Scotland, U K
Biochem J 460:127-39. 2014..kinase PINK1 (PTEN-induced putative kinase 1) is activated by mitochondrial depolarization and stimulates the Parkin E3 ligase by phosphorylating Ser65 within its Ubl (ubiquitin-like) domain...
- Parkin mitochondrial translocation is achieved through a novel catalytic activity coupled mechanismXinde 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. 2013Pink1, a mitochondrial kinase, and Parkin, an E3 ubiquitin ligase, function in mitochondrial maintenance...
- PINK1 drives Parkin self-association and HECT-like E3 activity upstream of mitochondrial bindingMichael 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. 2013Genetic studies indicate that the mitochondrial kinase PINK1 and the RING-between-RING E3 ubiquitin ligase Parkin function in the same pathway...
- Structure of the human Parkin ligase domain in an autoinhibited stateTobias Wauer
Division of Protein and Nucleic Acid Chemistry, Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
EMBO J 32:2099-112. 2013Mutations in the protein Parkin are associated with Parkinson's disease (PD), the second most common neurodegenerative disease in men...
- Mitofusin 1 and mitofusin 2 are ubiquitinated in a PINK1/parkin-dependent manner upon induction of mitophagyMatthew 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...
- Parkinson's disease-associated kinase PINK1 regulates Miro protein level and axonal transport of mitochondriaSong 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...
- Parkin is transcriptionally regulated by ATF4: evidence for an interconnection between mitochondrial stress and ER stressL Bouman
Adolf Butenandt Institute, Neurobiochemistry, Ludwig Maximilians University, Schillerstrasse 44, Munich, Germany
Cell Death Differ 18:769-82. 2011Loss 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...
- Loss of PINK1 function promotes mitophagy through effects on oxidative stress and mitochondrial fissionRuben 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...
- Genetic etiology of Parkinson disease associated with mutations in the SNCA, PARK2, PINK1, PARK7, and LRRK2 genes: a mutation updateKaren 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)...
- PINK1 autophosphorylation upon membrane potential dissipation is essential for Parkin recruitment to damaged mitochondriaKei 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...
- Structure and function of Parkin E3 ubiquitin ligase reveals aspects of RING and HECT ligasesB E Riley
Elan Pharmaceuticals, 180 Oyster Point Boulevard, South San Francisco, California 94080, USA
Nat Commun 4:1982. 2013b>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...
- Nix is critical to two distinct phases of mitophagy, reactive oxygen species-mediated autophagy induction and Parkin-ubiquitin-p62-mediated mitochondrial primingWen 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...
- Mitochondrial processing peptidase regulates PINK1 processing, import and Parkin recruitmentAndrew 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...
- The E3 ligase parkin maintains mitochondrial integrity by increasing linear ubiquitination of NEMOAnne Kathrin Müller-Rischart
Neurobiochemistry, Adolf Butenandt Institute, Ludwig Maximilians University, 80336 Munich, Germany
Mol Cell 49:908-21. 2013b>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...
- Parkin overexpression selects against a deleterious mtDNA mutation in heteroplasmic cybrid cellsDer 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 ..
- Parkin mono-ubiquitinates Bcl-2 and regulates autophagyDong 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. 2010b>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...
- Parkin-induced mitophagy in the pathogenesis of Parkinson diseaseDerek 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. 2009Knockout of the ubiquitin ligase Parkin, the gene product of the Parkinson associated Park2, leads to loss of mitochondrial integrity and function in Drosophila melanogaster...
- Parkin stabilizes PINK1 through direct interactionKahori Shiba
Research Institute for Diseases of Old Age, Juntendo University School of Medicine, Hongo, Bunkyo, Tokyo, Japan
Biochem Biophys Res Commun 383:331-5. 2009..Multiple genes mediating familial forms of Parkinson's disease (PD) have been identified, such as parkin (PARK2) and phosphatase and tensin homologue deleted on chromosome ten (PTEN)-induced putative kinase 1: PINK1 (..
- Differential expression of alpha-synuclein, parkin, and synphilin-1 isoforms in Lewy body diseaseKatrin Beyer
Department of Pathology, Hospital Germans Trias i Pujol, Autonomous University of Barcelona, Barcelona, Spain
Neurogenetics 9:163-72. 2008Alpha-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...
- Diverse effects of pathogenic mutations of Parkin that catalyze multiple monoubiquitylation in vitroNoriyuki Matsuda
Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo ku, Tokyo 113 8613
J Biol Chem 281:3204-9. 2006Mutational 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...
- Effect of endogenous mutant and wild-type PINK1 on Parkin in fibroblasts from Parkinson disease patientsAleksandar Rakovic
Section of Clinical and Molecular Neurogenetics, Department of Neurology, University of Lubeck, 23562 Lübeck, Germany
Hum Mol Genet 19:3124-37. 2010Mutations 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)...
- CHIP is associated with Parkin, a gene responsible for familial Parkinson's disease, and enhances its ubiquitin ligase activityYuzuru Imai
Laboratory for Motor System Neurodegeneration, RIKEN Brain Science Institute, Saitama 351 0198, Japan
Mol Cell 10:55-67. 2002Unfolded 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...
- Inhibition of mitochondrial fusion by α-synuclein is rescued by PINK1, Parkin and DJ-1Frits 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.
- Phosphorylation of parkin by Parkinson disease-linked kinase PINK1 activates parkin E3 ligase function and NF-kappaB signalingDi Sha
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA
Hum Mol Genet 19:352-63. 2010Mutations 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 ..
- PINK1 is recruited to mitochondria with parkin and associates with LC3 in mitophagySumihiro 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...
- Parkin ubiquitinates Drp1 for proteasome-dependent degradation: implication of dysregulated mitochondrial dynamics in Parkinson diseaseHongxia Wang
Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, Tianjin, China
J Biol Chem 286:11649-58. 2011Mutations 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 ..
- A molecular explanation for the recessive nature of parkin-linked Parkinson's diseaseDonald E Spratt
Department of Biochemistry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada N6A 5C1
Nat Commun 4:1983. 2013Mutations in the park2 gene, encoding the RING-inBetweenRING-RING E3 ubiquitin ligase parkin, cause 50% of autosomal recessive juvenile Parkinsonism cases...
- Alpha-synuclein and parkin contribute to the assembly of ubiquitin lysine 63-linked multiubiquitin chainsEllen W Doss-Pepe
Department of Biochemistry, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA
J Biol Chem 280:16619-24. 2005Mutations in alpha-synuclein, Parkin, and UCH-L1 cause heritable forms of Parkinson disease...
- 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-1Eric 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. 2013b>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...
- Structure and Function of Parkin, PINK1, and DJ-1, the Three Musketeers of NeuroprotectionJean Francois Trempe
McGill Parkinson Program, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University Montreal, QC, Canada
Front Neurol 4:38. 2013Autosomal 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...
- Phosphorylation of Parkin at Serine65 is essential for activation: elaboration of a Miro1 substrate-based assay of Parkin E3 ligase activityAgne Kazlauskaite
MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UK
Open Biol 4:130213. 2014Mutations in PINK1 and Parkin are associated with early-onset Parkinson's disease...
- Lysine 27 ubiquitination of the mitochondrial transport protein Miro is dependent on serine 65 of the Parkin ubiquitin ligaseNicol 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...
- Parkin mediates nonclassical, proteasomal-independent ubiquitination of synphilin-1: implications for Lewy body formationKah Leong Lim
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Neurosci 25:2002-9. 2005It 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...
- Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligaseH 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...
- Accumulation of the authentic parkin substrate aminoacyl-tRNA synthetase cofactor, p38/JTV-1, leads to catecholaminergic cell deathHan Seok Ko
Institute for Cell Engineering, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Neurosci 25:7968-78. 2005Autosomal-recessive juvenile parkinsonism (AR-JP) is caused by loss-of-function mutations of the parkin gene...
- Mutations in PINK1 and Parkin impair ubiquitination of Mitofusins in human fibroblastsAleksandar Rakovic
Section of Clinical and Molecular Neurogenetics, Department of Neurology, University of Lubeck, Lubeck, Germany
PLoS ONE 6:e16746. 2011PINK1 and Parkin mutations cause recessive Parkinson's disease (PD)...
- Parkin promotes degradation of the mitochondrial pro-apoptotic ARTS proteinStav 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...
- Parkin facilitates the elimination of expanded polyglutamine proteins and leads to preservation of proteasome functionYien Che Tsai
Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD 21205, USA
J Biol Chem 278:22044-55. 2003b>Parkin, the most commonly mutated gene in familial Parkinson's disease, encodes an E3 ubiquitin ligase...
- Mitochondrial function and morphology are impaired in parkin-mutant fibroblastsHeather Mortiboys
Academic Neurology Unit, Medical School, University of Sheffield, Sheffield, United Kingdom
Ann Neurol 64:555-65. 2008There 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...
- 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 DiseaseN 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 ..
- 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-synucleinXiao 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. 2009Recessive mutations in parkin are the most common cause of familial early-onset Parkinson's disease (PD)...
- Parkin binds the Rpn10 subunit of 26S proteasomes through its ubiquitin-like domainEri 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. 2003b>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...
- Parkin binds to alpha/beta tubulin and increases their ubiquitination and degradationYong 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 ..
- Somatic mutations of the Parkinson's disease-associated gene PARK2 in glioblastoma and other human malignanciesSelvaraju Veeriah
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA
Nat Genet 42:77-82. 2010Mutation of the gene PARK2, which encodes an E3 ubiquitin ligase, is the most common cause of early-onset Parkinson's disease...
- The PINK1/Parkin-mediated mitophagy is compromised by PD-associated mutationsSven 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)...
- Parkin accumulation in aggresomes due to proteasome impairmentEunsung 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...
- Restriction of trophic factors and nutrients induces PARKIN expressionM Klinkenberg
Experimental Neurology, Department of Neurology, University Medical School, Goethe University, Heinrich Hoffmann Str 7, 60528, Frankfurt am Main, Germany
Neurogenetics 13:9-21. 2012..Especially the mitochondrial kinase PINK1 and the ubiquitin ligase PARKIN are known to cooperate in autophagy after mitochondrial damage...
- The importance of Wnt signalling for neurodegeneration in Parkinson's diseaseDaniel C Berwick
Department of Pharmacology, UCL School of Pharmacy, University College London, 29 39 Brunswick Square, London WC1N 1AX, U K
Biochem Soc Trans 40:1123-8. 2012..This suggests the prospect of targeting Wnt signalling pathways to modify PD progression...
- Molecular interaction between parkin and PINK1 in mammalian neuronal cellsJi 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...
- Ataxin-3 deubiquitination is coupled to Parkin ubiquitination via E2 ubiquitin-conjugating enzymeThomas 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. 2012We reported previously that parkin, a Parkinson disease-associated E3 ubiquitin-ligase interacts with ataxin-3, a deubiquitinating enzyme associated with Machado-Joseph disease...
- 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-1M 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...
- Systematic review and UK-based study of PARK2 (parkin), PINK1, PARK7 (DJ-1) and LRRK2 in early-onset Parkinson's diseaseLaura 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...
- Co-association of parkin and alpha-synucleinP Choi
Department of Pharmacology, Loyola University Medical Center, Bldg 102, Rm 3634, 2160 S 1st Ave, Maywood, IL 60153, USA
Neuroreport 12:2839-43. 2001b>Parkin and alpha-synuclein are two proteins that are associated with the pathophysiology of Parkinson's disease (PD)...
- The p38 subunit of the aminoacyl-tRNA synthetase complex is a Parkin substrate: linking protein biosynthesis and neurodegenerationOlga 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 ..
- 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 GroupJ Tassin
INSERM U289, Hôpital de la Salpêtière, Paris, France
Am J Hum Genet 63:88-94. 1998..We have confirmed linkage of AR-JP, in European families and in an Algerian family, to the PARK2 locus. PARK2 appears to be an important locus for AR-JP in European patients...
- The C289G and C418R missense mutations cause rapid sequestration of human Parkin into insoluble aggregatesWen Jie Gu
INSERM U 289, Hopital de la Salpetriere, 75013 Paris, France
Neurobiol Dis 14:357-64. 2003Mutations 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...
- PARK2/PACRG polymorphisms and susceptibility to typhoid and paratyphoid feverS Ali
Department of Infectious Diseases, Leiden University Medical Centre, The Netherlands
Clin Exp Immunol 144:425-31. 2006..Recently polymorphisms in PARK2/PACRG, a gene cluster linked to ubiquitination and proteasome-mediated protein degradation, were found to be ..
- Interaction between parkin and mutant glucocerebrosidase variants: a possible link between Parkinson disease and Gaucher diseaseIdit 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...
- Familial-associated mutations differentially disrupt the solubility, localization, binding and ubiquitination properties of parkinSathya R Sriram
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Hum Mol Genet 14:2571-86. 2005Mutations in parkin are largely associated with autosomal recessive juvenile parkinsonism...
- Relative sensitivity of parkin and other cysteine-containing enzymes to stress-induced solubility alterationsEsther 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. 2007Loss 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...
- Association between early-onset Parkinson's disease and mutations in the parkin geneC B Lücking
INSERM Unité 289, Hopital de la Salpetriere, Paris
N Engl J Med 342:1560-7. 2000Mutations 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.
- Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin-protein ligase activityY Imai
Laboratory for Motor System Neurodegeneration, RIKEN Brain Science Institute BSI, Saitama 351 0198, Japan
J Biol Chem 275:35661-4. 2000Autosomal recessive juvenile parkinsonism (AR-JP) is caused by mutations in the parkin gene...
- Parkin and CASK/LIN-2 associate via a PDZ-mediated interaction and are co-localized in lipid rafts and postsynaptic densities in brainLara Fallon
Centre for Neuronal Survival, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada
J Biol Chem 277:486-91. 2002Mutations in the gene encoding parkin cause an autosomal recessive juvenile-onset form of Parkinson's disease...
- Parkin selectively alters the intrinsic threshold for mitochondrial cytochrome c releaseAlison K Berger
Neurology, Brigham and Women s Hospital, Boston, MA 02115, USA
Hum Mol Genet 18:4317-28. 2009Autosomal-recessive mutations in the Parkin gene are the second most common cause of familial Parkinson's disease (PD)...
- Features of the parkin/ariadne-like ubiquitin ligase, HHARI, that regulate its interaction with the ubiquitin-conjugating enzyme, Ubch7H 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...
- Parkin protects human dopaminergic neuroblastoma cells against dopamine-induced apoptosisHoubo 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...
- Dopamine covalently modifies and functionally inactivates parkinMatthew 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. 2005Inherited 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...
- Biochemical analysis of Parkinson's disease-causing variants of Parkin, an E3 ubiquitin-protein ligase with monoubiquitylation capacityCornelia Hampe
Neurologie et Thérapeutique Expérimentale, INSERM U679 Université Pierre and Marie Curie, Paris, France
Hum Mol Genet 15:2059-75. 2006Mutations 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...
- Transcriptional repression of p53 by parkin and impairment by mutations associated with autosomal recessive juvenile Parkinson's diseaseCristine 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. 2009Mutations 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...
- Influence of heterozygosity for parkin mutation on onset age in familial Parkinson disease: the GenePD studyMei Sun
Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA
Arch Neurol 63:826-32. 2006The PARK2 gene at 6q26 encodes parkin, whose inactivation is implicated in an early-onset autosomal recessive form of Parkinson disease (PD).
- Leucine-Rich Repeat Kinase 2 interacts with Parkin, DJ-1 and PINK-1 in a Drosophila melanogaster model of Parkinson's diseaseKaterina 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.
- Parkin functions as an E2-dependent ubiquitin- protein ligase and promotes the degradation of the synaptic vesicle-associated protein, CDCrel-1Y 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 ..
- Parkin mutations and susceptibility alleles in late-onset Parkinson's diseaseSofia 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. 2003b>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...
- Parkin mediates neuroprotection through activation of IkappaB kinase/nuclear factor-kappaB signalingIris H Henn
Department of Biochemistry, Adolf Butenandt Institute, D 80336 Munich, Germany
J Neurosci 27:1868-78. 2007Mutations 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...
- Parkin-mediated monoubiquitination of the PDZ protein PICK1 regulates the activity of acid-sensing ion channelsMonica 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. 2007Mutations 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...
- Disease-causing mutations in parkin impair mitochondrial ubiquitination, aggregation, and HDAC6-dependent mitophagyJoo Yong Lee
Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA
J Cell Biol 189:671-9. 2010Mutations in parkin, a ubiquitin ligase, cause early-onset familial Parkinson's disease (AR-JP). How parkin suppresses parkinsonism remains unknown...
- p62/SQSTM1 is required for Parkin-induced mitochondrial clustering but not mitophagy; VDAC1 is dispensable for bothDerek 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 ..
- Rare heterozygous parkin variants in French early-onset Parkinson disease patients and controlsS Lesage
J Med Genet 45:43-6. 2008Mutations in the parkin gene cause autosomal recessive early-onset parkinsonism. The effect of single heterozygous mutations in parkin is still unclear...
- Parkin analysis in early onset Parkinson's diseaseFrancesca Sironi
Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy
Parkinsonism Relat Disord 14:326-33. 2008We 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...
- Role of parkin mutations in 111 community-based patients with early-onset parkinsonismMartin Kann
Department of Neurology, Medical University of Lubeck, Lubeck, Germany
Ann Neurol 51:621-5. 2002Early-onset parkinsonism is frequently reported in connection with mutations in the parkin gene...
- Bilateral subthalamic stimulation in Parkin and PINK1 parkinsonismE Moro
Movement Disorder Centre, Toronto Western Hospital, University of Toronto, Ontario, Canada
Neurology 70:1186-91. 2008....
- Parkin mutations and phenotypic features in Czech patients with early-onset Parkinson's diseaseOndrej Fiala
Department of Neurology, 1st Medical Faculty and General Teaching Hospital, Charles University, Prague, Czech Republic
Neuro Endocrinol Lett 31:187-92. 2010Mutations in several genes such as parkin can be detected in up to 20% of patients with early-onset Parkinson's disease (EOPD)...
- Solution structure of the E3 ligase HOIL-1 Ubl domainSteven A Beasley
Department of Biochemistry, University of Western Ontario, London, Ontario N6A 5C1, Canada
Protein Sci 21:1085-92. 2012The 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...
- Does parkin play a role in the peripheral nervous system? A family reportGiovanni Abbruzzese
Department of Neuroscience, Ophthalmology and Genetics, Section of Neurology, University of Genova, Italy
Mov Disord 19:978-81. 2004Two genes were identified for autosomal recessive forms of early onset Parkinson's disease: parkin and DJ-1...
- Identification of far upstream element-binding protein-1 as an authentic Parkin substrateHan 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...
- Parkin mutations in a patient with hemiparkinsonism-hemiatrophy: a clinical-genetic and PET studyP 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 ..
- 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. 2006Mutations in the parkin gene are a common cause of autosomal recessive, juvenile or early onset parkinsonism (PARK2)...
- Caspase-1 and caspase-8 cleave and inactivate cellular parkinSoren Kahns
Department of Molecular Biology, University of Aarhus, DK 8000 Aarhus C, Denmark
J Biol Chem 278:23376-80. 2003Lesions 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...
- Parkin interacts with LIM Kinase 1 and reduces its cofilin-phosphorylation activity via ubiquitinationMeng K Lim
Department of Molecular Biology, Keio University School of Medicine, 35 Shinanomachi, Tokyo, Japan
Exp Cell Res 313:2858-74. 2007Mutations 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)...
- Differential interaction of the E3 ligase parkin with the proteasomal subunit S5a and the endocytic protein Eps15Susan S Safadi
Department of Biochemistry, The University of Western Ontario, London, Ontario N6A 5C1, Canada
J Biol Chem 285:1424-34. 2010b>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...
- Parkin directly modulates 26S proteasome activityJi 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...
Research Grants105 found, 100 shown here
- The Roles of a-Synuclein and Parkin in Parkinson DiseaseMichael Schlossmacher; Fiscal Year: 2005..The PARK2 gene encodes parkin, an E3 ubiquitin ligase...
- Yi Sun; Fiscal Year: 2016..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. ..
- Inflammatory Proteases, Ubiquitin Proteasome System, and Myocyte DeathAbdelkarim Sabri; Fiscal Year: 2012....
- Richard K Bruick; Fiscal Year: 2014..To that end, this proposal describes the characterization of a candidate sensor and regulator of mammalian iron homeostasis, FBXL5. ..
- REGULATION OF DEFENSE SIGNALING IN TOMATOGregg A Howe; Fiscal Year: 2012....
- Gregory B Martin; Fiscal Year: 2014..The knowledge gained will contribute to strategies to lessen the impact of bacterial diseases of importance to both agriculture and human health. ..
- Structural Biology of U-box E3 Ubiquitin LigasesWalter 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. ..
- Michael N Boddy; Fiscal Year: 2016..Additionally, a detailed understanding of STUbL function should yield general implications for responses to genotoxic stress. ..
- Partitioning of Misfolded Membrane Proteins Between Different Degradatory FatesSCOTT 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. ..
- Nedd4-family ubiquitination networks that regulate T cell functionPAULA 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. ..
- Mechanisms of protein degradation and transcriptional regulation by ubiquitin modChristopher 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. ..
- ARUN KUMAR RISHI; Fiscal Year: 2016..abstract_text> ..
- Mechanism of Gli3 processing in Hedgehog signalingBaolin 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. ..
- Regulators and mediators of TRIM5 functionJacek 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. ..
- STEROID CONTROL OF EPITHELIAL CELL-CELL INTERACTIONSGary 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. ..
- Claudio A P Joazeiro; Fiscal Year: 2016..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. ..
- Zhen Qiang Pan; Fiscal Year: 2014....
- MODULATION OF NF-kB ACTIVATION BY A NOVEL MITOCHONDRIAL E3 UBIQUITIN LIGASEClaudio 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. ..
- 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...
- Cellular &Inflammatory Pathways in Ashtma &Allergic Diseases: From IgE to CellsLAWRENCE 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. ..
- REGULATION AND FUNCTION OF STE20-RELATED PROTEIN KINASESMelanie 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. ..
- Role of Natural Killer Lytic-Associated Molecule (NKLAM) in Natural Killer FunctiJacki 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. ..
- Hermann Steller; Fiscal Year: 2016..Therefore, this project will have profound implications for both basic science and medicine. ..
- Programmed Cell Death and Disease Resistance in ArabidopsisRoger 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. ..
- Peter M Snyder; Fiscal Year: 2016..This may have important implications for our understanding and treatment of diseases including hypertension and cystic fibrosis. ..
- Yi Sun; Fiscal Year: 2016....
- Matthew P DeLisa; Fiscal Year: 2014....
- Structural studies of cullin-based ubiquitin ligasesNing Zheng; Fiscal Year: 2013....
- TIMOTHY AN THY CHAN; Fiscal Year: 2015Project Summary/Abstract Title: The role of the Parkinson's disease gene PARK2 in GBM oncogenesis and genomic instability Glioblastoma (GBM) is a primary malignancy of the central nervous system that is nearly universally fatal...
- Yue Xiong; Fiscal Year: 2016..Finally, we propose to determine broadly the function of CUL4B in the regulation of chromatin modification and gene expression. ..
- Shao Cong Sun; Fiscal Year: 2016....
- TAREK A ABBAS; Fiscal Year: 2014..The results will advance our understanding of how to exploit the regulated process of protein ubiquitylation and proteolysis for cancer intervention purposes. ..
- E3 Ubiquitin Ligase Functions in Enveloped Virus BuddingANDREW 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. ..
- Alteration of host protein stability by LegionellaMichael 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. ..
- DON MICHAEL WOJCHOWSKI; Fiscal Year: 2016..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. ..
- Melissa A Kacena; Fiscal Year: 2015..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. ..
- Quantitative Analysis of RING E3 Ubiquitin LigasesCHARLES 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. ..
- Sudha K Shenoy; Fiscal Year: 2014..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. ..
- Biology of nuclear receptor rev-erb alpha in circadian rhythm and metabolismLei Yin; Fiscal Year: 2009..In addition, this work may shed the new light on identifying new therapeutic targets for treating insulin resistance and diabetes. ..
- Biology of nuclear receptor rev-erb alpha in circadian rhythm and metabolismLei 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. ..
- Wenqing Xu; Fiscal Year: 2015..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. ..
- Judith A Steen; Fiscal Year: 2014..abstract_text> ..
- Jun Ichi Abe; Fiscal Year: 2014..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. ..
- Cyrus Vaziri; Fiscal Year: 2016..g. Rad18 or its activating kinases) whose inhibition enhances the efficacy of existing cancer therapies. ..
- Gary L Firestone; Fiscal Year: 2015..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. ..
- L2DTL Function in Maintaining Genomic Stability during Drosophila DevelopmentCATHERINE SILVER KEY; Fiscal Year: 2010..Experiment results should support the hypothesis that L2DTL is essential for preventing re-replication in all cell contexts. ..
- Wei Gu; Fiscal Year: 2016..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. ..
- Anna Moszczynska; Fiscal Year: 2016..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 ..
- Randolph Y Hampton; Fiscal Year: 2014..Our studies will define those functions and eventually the ways to harness or quell them for basic and biomedical benefit. ..
- Kenneth R Hallows; Fiscal Year: 2015....
- The function and regulation of the cullin family E3 ubiquitin ligasesZhen Qiang Pan; Fiscal Year: 2012....
- Xinnian Dong; Fiscal Year: 2016....
- Mechanism, regulation and function of PP2A ubiquitinationBrian E Wadzinski; Fiscal Year: 2010..abstract_text> ..
- Ming Hui Zou; Fiscal Year: 2015....
- Hiroyuki Inuzuka; Fiscal Year: 2015..We expect this will provide evidence toward the rationale for using mTOR pharmacological intervention in personalized medicine for age-related diseases. ..
- Posttranslational processing of tau: function & dysfunc.Gail Johnson; Fiscal Year: 2009..abstract_text> ..
- Michael B Kastan; Fiscal Year: 2016....
- David J Pintel; Fiscal Year: 2015..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. ..
- Tegument ICP0 and HSV EntryAnthony V Nicola; Fiscal Year: 2010..Greater understanding of the virus entry process may help to develop novel approaches to prevent herpes infections. ..
- Differential regulation of cardiomyocyte survival and hypertrophyPeter 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. ..
- Khadija Rafiq; Fiscal Year: 2016....
- Osteopontin regulates ubiquitin-proteasome degradation of STAT1Paul C Kuo; Fiscal Year: 2012..Characterization of this regulatory pathway may identify potential regulatory targets for therapy in septic shock. ..
- Coordinated regulation of MAP kinase signaling by ubiquitinationJILLIAN 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. ..
- Iannis Aifantis; Fiscal Year: 2016..Finally, we study both in vitro and in vivo the effect of Fbw7 mutations on gamma-secretase inhibitor treatment of T-ALL. ..
- Spinocerebellar Ataxia Type 2 Gene and Gene ProductStefan 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...
- Mitchell Kronenberg; Fiscal Year: 2014..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. ..
- Substrates and Binding Partners in the PINK1/Parkin PathwayDerek P Narendra; Fiscal Year: 2011..Loss of function mutations in PINK1 and Parkin cause familial parkinsonism (3, 4)...
- Chou Zen Giam; Fiscal Year: 2014..The study will provide molecular insights that can lead to the development of treatment strategies for human cancer ..
- Jordan A Kreidberg; Fiscal Year: 2014..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. ..
- ANDREW GEORGE MUNTEAN; Fiscal Year: 2014..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. ..
- David Kuhrt; Fiscal Year: 2015..This trainin plan is designed to advance impacting first author papers and expertise as a new independent investigator. ..
- Hypoxia and Anticancer Drug ActionGarth Powis; Fiscal Year: 2013..abstract_text> ..
- B-RAF Regulation of the Cell Cycle in MelanomaAndrew 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. ..
- CATHERINE KOTO; Fiscal Year: 2014....
- CLARISSA LEIGH WAITES; Fiscal Year: 2016..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. ..
- Zhiguo Zhang; Fiscal Year: 2015....
- Matthew P Anderson; Fiscal Year: 2016..The novel molecular insights and genetic tools will facilitate development of treatments for these life-long behavioral disabilities. ..
- JENNIFER LYNN STRIPAY; Fiscal Year: 2015..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. ..
- Wenyi Wei; Fiscal Year: 2016..Instead, our studies will inform the use of Cdk2, Skp2 and Akt inhibitors for targeted therapy to achieve optimal treatment efficacy in the clinic. ..
- Matthew D Weitzman; Fiscal Year: 2016..Knowledge of HSV-1 neuronal latency will suggest novel targets for developing antivirals against this significant human pathogen. ..
- Identification of the protein homeostasis network that controls the quality contrCHRISTINE MARIE LIVINGSTON; Fiscal Year: 2013....
- Christina Tenenhaus Dann; Fiscal Year: 2016....
- AUNDRIETTA DE VAN DUNCAN; Fiscal Year: 2015..This information can be value in the potential use of TRIM24 as a diagnostic marker and therapeutic target. ..
- RACHEL HESLER; Fiscal Year: 2015..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. ..
- Tien Hsu; Fiscal Year: 2015..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. ..
- Cytochrome c Degradation: A Mechanism to Restrict Apoptosis in Postmitotic CellsMohanish Deshmukh; Fiscal Year: 2013....
- Chunhong Yan; Fiscal Year: 2015....
- Jan M van Deursen; Fiscal Year: 2016....
- Virginia Smith Shapiro; Fiscal Year: 2016....
- Gary L Johnson; Fiscal Year: 2015..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. ..
- Novel Regulators of Bone FormationLAURIE 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. ..
- The HydroxylprolylproteomeFrank S Lee; Fiscal Year: 2013..abstract_text> ..
- Shi Yong Sun; Fiscal Year: 2015..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. ..
- Cell-autonomous mechanisms of Ube3a function in the neocortexMATTHEW 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. ..
- The Seventh International Mdm2 WorkshopJames 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. ..
- Chou Zen Giam; Fiscal Year: 2014..The study will provide molecular insights that can lead to the development of treatment strategies for human cancer. ..
- Genetic Control of Axial Patterning in Drosophila EyeAmit 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. ..
- E2 selectivity and activation by CHIPSARAH 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. ..
- Role of Parkin in Regulating Manganese ToxicityJEROME 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 ..
- TRAF6 E3 LIGASE FUNCTION IN OSTEOCLASTOGENESISBryant 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 ..
- Salmonella SopA is a functional mimicry of eukaryotic E3 protein ubiquitin ligaseDaoguo Zhou; Fiscal Year: 2010..Results from this study will help us understand how Salmonella induces intestinal inflammation in humans. ..