ubiquitin

Summary

Summary: A highly conserved 76-amino acid peptide universally found in eukaryotic cells that functions as a marker for intracellular PROTEIN TRANSPORT and degradation. Ubiquitin becomes activated through a series of complicated steps and forms an isopeptide bond to lysine residues of specific proteins within the cell. These "ubiquitinated" proteins can be recognized and degraded by proteosomes or be transported to specific compartments within the cell.

Top Publications

  1. ncbi p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy
    Serhiy Pankiv
    Biochemistry Department, Institute of Medical Biology, University of Tromsø, 9037 Tromsø, Norway
    J Biol Chem 282:24131-45. 2007
  2. pmc p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death
    Geir Bjørkøy
    Biochemistry Department, Institute of Medical Biology, University of Tromsø, 9037 Tromsø, Norway
    J Cell Biol 171:603-14. 2005
  3. ncbi Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis
    Manuela Neumann
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Science 314:130-3. 2006
  4. ncbi Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice
    Taichi Hara
    Department of Bioregulation and Metabolism, Tokyo Metropolitan Institute of Medical Science, Tokyo 113 8613, Japan
    Nature 441:885-9. 2006
  5. ncbi RING domain E3 ubiquitin ligases
    Raymond J Deshaies
    Howard Hughes Medical Institute and Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    Annu Rev Biochem 78:399-434. 2009
  6. ncbi Loss of autophagy in the central nervous system causes neurodegeneration in mice
    Masaaki Komatsu
    Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo ku, Tokyo 113 8613, Japan
    Nature 441:880-4. 2006
  7. ncbi The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction
    Michael H Glickman
    Faculty of Biology and the Institute for Catalysis Science and Technology, Haifa, Israel
    Physiol Rev 82:373-428. 2002
  8. pmc Systematic and quantitative assessment of the ubiquitin-modified proteome
    Woong Kim
    Department of Cell Biology, Harvard Medical School, Boston, MA, USA
    Mol Cell 44:325-40. 2011
  9. pmc Autism genome-wide copy number variation reveals ubiquitin and neuronal genes
    Joseph T Glessner
    Center for Applied Genomics, Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
    Nature 459:569-73. 2009
  10. pmc Defining the human deubiquitinating enzyme interaction landscape
    Mathew E Sowa
    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Cell 138:389-403. 2009

Detail Information

Publications343 found, 100 shown here

  1. ncbi p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy
    Serhiy Pankiv
    Biochemistry Department, Institute of Medical Biology, University of Tromsø, 9037 Tromsø, Norway
    J Biol Chem 282:24131-45. 2007
    ..In fact, p62 bodies and these structures are indistinguishable. Taken together, our results clearly suggest that p62 is required both for the formation and the degradation of polyubiquitin-containing bodies by autophagy...
  2. pmc p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death
    Geir Bjørkøy
    Biochemistry Department, Institute of Medical Biology, University of Tromsø, 9037 Tromsø, Norway
    J Cell Biol 171:603-14. 2005
    ..We suggest that p62 may, via LC3, be involved in linking polyubiquitinated protein aggregates to the autophagy machinery...
  3. ncbi Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis
    Manuela Neumann
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Science 314:130-3. 2006
    b>Ubiquitin-positive, tau- and alpha-synuclein-negative inclusions are hallmarks of frontotemporal lobar degeneration with ubiquitin-positive inclusions and amyotrophic lateral sclerosis...
  4. ncbi Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice
    Taichi Hara
    Department of Bioregulation and Metabolism, Tokyo Metropolitan Institute of Medical Science, Tokyo 113 8613, Japan
    Nature 441:885-9. 2006
    ....
  5. ncbi RING domain E3 ubiquitin ligases
    Raymond J Deshaies
    Howard Hughes Medical Institute and Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    Annu Rev Biochem 78:399-434. 2009
    E3 ligases confer specificity to ubiquitination by recognizing target substrates and mediating transfer of ubiquitin from an E2 ubiquitin-conjugating enzyme to substrate...
  6. ncbi Loss of autophagy in the central nervous system causes neurodegeneration in mice
    Masaaki Komatsu
    Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo ku, Tokyo 113 8613, Japan
    Nature 441:880-4. 2006
    ..In addition to the ubiquitin-proteasome system, emerging evidence points to the importance of autophagy--the bulk protein degradation pathway ..
  7. ncbi The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction
    Michael H Glickman
    Faculty of Biology and the Institute for Catalysis Science and Technology, Haifa, Israel
    Physiol Rev 82:373-428. 2002
    ..The discovery of the complex cascade of the ubiquitin pathway revolutionized the field...
  8. pmc Systematic and quantitative assessment of the ubiquitin-modified proteome
    Woong Kim
    Department of Cell Biology, Harvard Medical School, Boston, MA, USA
    Mol Cell 44:325-40. 2011
    ..To globally characterize the human ubiquitin-modified proteome (ubiquitinome), we utilized a monoclonal antibody that recognizes diglycine (diGly)-containing ..
  9. pmc Autism genome-wide copy number variation reveals ubiquitin and neuronal genes
    Joseph T Glessner
    Center for Applied Genomics, Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
    Nature 459:569-73. 2009
    ..5 x 10(-3)). Furthermore, CNVs within or surrounding genes involved in the ubiquitin pathways, including UBE3A, PARK2, RFWD2 and FBXO40, were affected by CNVs not observed in controls (P = 3...
  10. pmc Defining the human deubiquitinating enzyme interaction landscape
    Mathew E Sowa
    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Cell 138:389-403. 2009
    Deubiquitinating enzymes (Dubs) function to remove covalently attached ubiquitin from proteins, thereby controlling substrate activity and/or abundance. For most Dubs, their functions, targets, and regulation are poorly understood...
  11. pmc Regulation and cellular roles of ubiquitin-specific deubiquitinating enzymes
    Francisca E Reyes-Turcu
    Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Annu Rev Biochem 78:363-97. 2009
    Deubiquitinating enzymes (DUBs) are proteases that process ubiquitin or ubiquitin-like gene products, reverse the modification of proteins by a single ubiquitin(-like) protein, and remodel polyubiquitin(-like) chains on target proteins...
  12. ncbi TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis
    Tetsuaki Arai
    Department of Psychogeriatrics, Tokyo Institute of Psychiatry, Setagaya Ku, Tokyo 156 8585, Japan
    Biochem Biophys Res Commun 351:602-11. 2006
    b>Ubiquitin-positive tau-negative neuronal cytoplasmic inclusions and dystrophic neurites are common pathological features in frontotemporal lobar degeneration (FTLD) with or without symptoms of motor neuron disease and in amyotrophic ..
  13. pmc Structure of a RING E3 ligase and ubiquitin-loaded E2 primed for catalysis
    Anna Plechanovova
    Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
    Nature 489:115-20. 2012
    b>Ubiquitin modification is mediated by a large family of specificity determining ubiquitin E3 ligases...
  14. 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
    Parkin, an E3 ubiquitin ligase implicated in Parkinson's disease, promotes degradation of dysfunctional mitochondria by autophagy...
  15. ncbi Ubiquitin-binding proteins: decoders of ubiquitin-mediated cellular functions
    Koraljka Husnjak
    Institute of Biochemistry II, School of Medicine, Goethe University, 60590 Frankfurt am Main, Germany
    Annu Rev Biochem 81:291-322. 2012
    b>Ubiquitin acts as a versatile cellular signal that controls a wide range of biological processes including protein degradation, DNA repair, endocytosis, autophagy, transcription, immunity, and inflammation...
  16. pmc Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice
    Masaaki Komatsu
    Department of Molecular Oncology, Tokyo Metropolitan Institute of Medical Science, Bunkyo ku, Tokyo 113 8613, Japan
    J Cell Biol 169:425-34. 2005
    ..such as appearance of concentric membranous structure and deformed mitochondria, and accumulation of ubiquitin-positive aggregates...
  17. pmc UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids
    Dawn M Wenzel
    Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA
    Nature 474:105-8. 2011
    Although the functional interaction between ubiquitin-conjugating enzymes (E2s) and ubiquitin ligases (E3s) is essential in ubiquitin (Ub) signalling, the criteria that define an active E2-E3 pair are not well established...
  18. ncbi RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins
    Carsten Doil
    Institute of Cancer Biology and Centre for Genotoxic Stress Research, Danish Cancer Society, Copenhagen, Denmark
    Cell 136:435-46. 2009
    ..RNF8 is necessary to trigger the DSB-associated ubiquitylations, it is not sufficient to sustain conjugated ubiquitin in this compartment...
  19. pmc One step at a time: endoplasmic reticulum-associated degradation
    Shruthi S Vembar
    Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
    Nat Rev Mol Cell Biol 9:944-57. 2008
    ..factors recognize and target substrates for retrotranslocation to the cytoplasm, where they are degraded by the ubiquitin-proteasome machinery...
  20. ncbi Emerging functions of the VCP/p97 AAA-ATPase in the ubiquitin system
    Hemmo Meyer
    Centre for Medical Biotechnology, Faculty of Biology, University of Duisburg Essen, 45117 Essen, Germany
    Nat Cell Biol 14:117-23. 2012
    The ATP-driven chaperone valosin-containing protein (VCP)/p97 governs critical steps in ubiquitin-dependent protein quality control and intracellular signalling pathways...
  21. ncbi A role for ubiquitin in selective autophagy
    Vladimir Kirkin
    Institute of Biochemistry II and Cluster of Excellence Macromolecular Complexes, Goethe University, Theodor Stern Kai 7, Frankfurt, Germany
    Mol Cell 34:259-69. 2009
    ..Identification of autophagy receptors, such as p62/SQSTM1 and NBR1, which simultaneously bind both ubiquitin and autophagy-specific ubiquitin-like modifiers, LC3/GABARAP, has provided a molecular link between ..
  22. ncbi Protein modification by SUMO
    Erica S Johnson
    Department of Biochemistry and Molecular Pharmacology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    Annu Rev Biochem 73:355-82. 2004
    Small ubiquitin-related modifier (SUMO) family proteins function by becoming covalently attached to other proteins as post-translational modifications...
  23. ncbi HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS
    Udai Bhan Pandey
    Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Nature 447:859-63. 2007
    ..Cellular mechanisms for degrading misfolded protein include the ubiquitin-proteasome system (UPS), the main non-lysosomal degradative pathway for ubiquitinated proteins, and autophagy, a ..
  24. ncbi Role of histone H2A ubiquitination in Polycomb silencing
    Hengbin Wang
    Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7295, USA
    Nature 431:873-8. 2004
    ..Here we report the purification and functional characterization of an E3 ubiquitin ligase complex that is specific for histone H2A...
  25. ncbi The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress
    Yoshiharu Kawaguchi
    Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA
    Cell 115:727-38. 2003
    ..These findings identify HDAC6 as a crucial player in the cellular management of misfolded protein-induced stress...
  26. ncbi The roles of intracellular protein-degradation pathways in neurodegeneration
    David C Rubinsztein
    Department of Medical Genetics, Cambridge Institute for Medical Research, Addenbrooke s Hospital, Hills Road, Cambridge CB2 2XY
    Nature 443:780-6. 2006
    ..The degradation pathways acting on such aggregate-prone cytosolic proteins include the ubiquitin-proteasome system and macroautophagy...
  27. pmc Recognition and processing of ubiquitin-protein conjugates by the proteasome
    Daniel Finley
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Annu Rev Biochem 78:477-513. 2009
    The proteasome is an intricate molecular machine, which serves to degrade proteins following their conjugation to ubiquitin. Substrates dock onto the proteasome at its 19-subunit regulatory particle via a diverse set of ubiquitin ..
  28. 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
    Parkin is an E3-ubiquitin ligase belonging to the RBR (RING-InBetweenRING-RING family), and is involved in the neurodegenerative disorder Parkinson's disease...
  29. ncbi RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation
    Michael H Tatham
    Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK
    Nat Cell Biol 10:538-46. 2008
    ..This disease can be treated effectively with arsenic, which induces PML modification by small ubiquitin-like modifiers (SUMO) and proteasomal degradation...
  30. ncbi Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex
    Ning Zheng
    Cellular Biochemistry and Biophysics Program, Memorial Sloan Kettering Cancer Center, New York 10021, USA
    Nature 416:703-9. 2002
    SCF complexes are the largest family of E3 ubiquitin-protein ligases and mediate the ubiquitination of diverse regulatory and signalling proteins...
  31. ncbi Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21
    Marc Cruts
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, Universiteitsplein 1, BE 2610 Antwerpen, Belgium
    Nature 442:920-4. 2006
    Frontotemporal dementia (FTD) with ubiquitin-immunoreactive neuronal inclusions (both cytoplasmic and nuclear) of unknown nature has been linked to a chromosome 17q21 region (FTDU-17) containing MAPT (microtubule-associated protein tau)...
  32. ncbi Regulation of DNA damage responses by ubiquitin and SUMO
    Stephen P Jackson
    The Gurdon Institute and the Department of Biochemistry, University of Cambridge, Cambridge, UK
    Mol Cell 49:795-807. 2013
    Ubiquitylation and sumoylation, the covalent attachment of the polypeptides ubiquitin and SUMO, respectively, to target proteins, are pervasive mechanisms for controlling cellular functions...
  33. pmc BIRC7-E2 ubiquitin conjugate structure reveals the mechanism of ubiquitin transfer by a RING dimer
    Hao Dou
    Beatson Institute for Cancer Research, Glasgow, UK
    Nat Struct Mol Biol 19:876-83. 2012
    Certain RING ubiquitin ligases (E3s) dimerize to facilitate ubiquitin (Ub) transfer from ubiquitin-conjugating enzyme (E2) to substrate, but structural evidence on how this process promotes Ub transfer is lacking...
  34. pmc The E3 ligase HOIP specifies linear ubiquitin chain assembly through its RING-IBR-RING domain and the unique LDD extension
    Judith J Smit
    Division of Biochemistry, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    EMBO J 31:3833-44. 2012
    Activation of the NF-κB pathway requires the formation of Met1-linked 'linear' ubiquitin chains on NEMO, which is catalysed by the Linear Ubiquitin Chain Assembly Complex (LUBAC) E3 consisting of HOIP, HOIL-1L and Sharpin...
  35. pmc Structure of an E3:E2~Ub complex reveals an allosteric mechanism shared among RING/U-box ligases
    Jonathan N Pruneda
    Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
    Mol Cell 47:933-42. 2012
    Despite the widespread importance of RING/U-box E3 ubiquitin ligases in ubiquitin (Ub) signaling, the mechanism by which this class of enzymes facilitates Ub transfer remains enigmatic...
  36. ncbi De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling
    Ingrid E Wertz
    Department of Molecular Oncology, School of Medicine, University of California, Davis, Davis, California 95616, USA
    Nature 430:694-9. 2004
    ..Here we show that A20 downregulates NF-kappaB signalling through the cooperative activity of its two ubiquitin-editing domains...
  37. ncbi The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses
    David L Boone
    Department of Medicine, University of California at San Francisco, San Francisco, California 94143 0451, USA
    Nat Immunol 5:1052-60. 2004
    ..A20 accomplished this biochemically by directly removing ubiquitin moieties from the signaling molecule TRAF6...
  38. ncbi Protein degradation and protection against misfolded or damaged proteins
    Alfred L Goldberg
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 426:895-9. 2003
    ..A full understanding of the pathogenesis of the protein-folding diseases will require greater knowledge of how misfolded proteins are recognized and selectively degraded...
  39. ncbi Principles of ubiquitin and SUMO modifications in DNA repair
    Steven Bergink
    Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany
    Nature 458:461-7. 2009
    With the discovery in the late 1980s that the DNA-repair gene RAD6 encodes a ubiquitin-conjugating enzyme, it became clear that protein modification by ubiquitin conjugation has a much broader significance than had previously been ..
  40. pmc Protein quality control in the ER: balancing the ubiquitin checkbook
    Jasper H L Claessen
    Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA
    Trends Cell Biol 22:22-32. 2012
    ..b>Ubiquitin conjugation is essential for both extraction and proteolysis...
  41. ncbi A role for NBR1 in autophagosomal degradation of ubiquitinated substrates
    Vladimir Kirkin
    Institute of Biochemistry II, Goethe University, Frankfurt Main, Germany
    Mol Cell 33:505-16. 2009
    ..Here we show that NBR1 (neighbor of BRCA1 gene 1) is an autophagy receptor containing LC3- and ubiquitin (Ub)-binding domains...
  42. ncbi Atg8, a ubiquitin-like protein required for autophagosome formation, mediates membrane tethering and hemifusion
    Hitoshi Nakatogawa
    Department of Cell Biology, National Institute for Basic Biology, Okazaki 444 8585, Japan
    Cell 130:165-78. 2007
    ..Atg8 is a ubiquitin-like protein required for this process in Saccharomyces cerevisiae that can be conjugated to the lipid ..
  43. pmc Autophagy inhibition compromises degradation of ubiquitin-proteasome pathway substrates
    Viktor I Korolchuk
    Department of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, Addenbrooke s Hospital, Cambridge, UK
    Mol Cell 33:517-27. 2009
    The two main routes that cells use for degrading intracellular proteins are the ubiquitin-proteasome and autophagy-lysosome pathways, which have been thought to have largely distinct clients...
  44. ncbi Nonproteolytic functions of ubiquitin in cell signaling
    Zhijian J Chen
    Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390 9148, USA
    Mol Cell 33:275-86. 2009
    The small protein ubiquitin is a central regulator of a cell's life and death. Ubiquitin is best known for targeting protein destruction by the 26S proteasome...
  45. ncbi The ubiquitous role of ubiquitin in the DNA damage response
    Abdallah Al-Hakim
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, M5G 1X5, ON, Canada
    DNA Repair (Amst) 9:1229-40. 2010
    ..In this review, we discuss how DNA repair and checkpoint pathways utilize the diversity offered by the ubiquitin conjugation system to modulate the response to genotoxic lesions in space and time...
  46. pmc Identification of the FANCI protein, a monoubiquitinated FANCD2 paralog required for DNA repair
    Agata Smogorzewska
    Department of Genetics, Howard Hughes Medical Institute, Center for Genetics and Genomics, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Cell 129:289-301. 2007
    ..Several FA proteins form a ubiquitin ligase that controls monoubiquitination of the FANCD2 protein in an ATR-dependent manner...
  47. ncbi Polycomb group proteins Ring1A/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation
    Mariana de Napoles
    Developmental Epigenetics Group, MRC Clinical Sciences Centre, ICFM, Hammersmith Hospital, DuCane Road, London W12 ONN, United Kingdom
    Dev Cell 7:663-76. 2004
    ..These observations link H2A ubiquitylation, X inactivation, and PRC1 PcG function, suggesting an unanticipated and novel mechanism for chromatin-mediated heritable gene silencing...
  48. ncbi Ubiquitin ligases: cell-cycle control and cancer
    Keiichi I Nakayama
    Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Fukuoka 812 8582, Japan
    Nat Rev Cancer 6:369-81. 2006
    ..cell cycle is the activation of cyclin-dependent kinases (CDKs), the activities of which are controlled by the ubiquitin-mediated proteolysis of key regulators such as cyclins and CDK inhibitors...
  49. ncbi Function and regulation of cullin-RING ubiquitin ligases
    Matthew D Petroski
    Division of Biology and Howard Hughes Medical Institute, California Institute of Technology, 1200 East California Boulevard, Pasadena, California 91125, USA
    Nat Rev Mol Cell Biol 6:9-20. 2005
    Cullin-RING complexes comprise the largest known class of ubiquitin ligases...
  50. ncbi Ubiquitin-binding domains in Y-family polymerases regulate translesion synthesis
    Marzena Bienko
    Institute for Biochemistry II, Goethe University Medical School, Theodor Stern Kai 7, 60590 Frankfurt, Germany
    Science 310:1821-4. 2005
    ..Here we describe the identification of two ubiquitin (Ub)-binding domains (UBM and UBZ), which are evolutionarily conserved in all Y-family TLS polymerases (pols)...
  51. pmc The RING-CH ligase K5 antagonizes restriction of KSHV and HIV-1 particle release by mediating ubiquitin-dependent endosomal degradation of tetherin
    Claire Pardieu
    MRC Centre for Medical Molecular Virology, University College London, London, United Kingdom
    PLoS Pathog 6:e1000843. 2010
    ..KSHV) is sensitive to tetherin restriction and its activity is counteracted by the KSHV encoded RING-CH E3 ubiquitin ligase K5...
  52. ncbi The TBK1 adaptor and autophagy receptor NDP52 restricts the proliferation of ubiquitin-coated bacteria
    Teresa L M Thurston
    Medical Research Council Laboratory of Molecular Biology, Division of Protein and Nucleic Acid Chemistry, Cambridge, UK
    Nat Immunol 10:1215-21. 2009
    ..Here we show that NDP52, not previously known to contribute to innate immunity, recognizes ubiquitin-coated Salmonella enterica in human cells and, by binding the adaptor proteins Nap1 and Sintbad, recruits TBK1...
  53. pmc HDAC6 controls autophagosome maturation essential for ubiquitin-selective quality-control autophagy
    Joo Yong Lee
    Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA
    EMBO J 29:969-80. 2010
    ..Here, we identify the ubiquitin-binding deacetylase, histone deacetylase-6 (HDAC6), as a central component of basal autophagy that targets ..
  54. ncbi Protein aggregation and neurodegenerative disease
    Christopher A Ross
    Division of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Ross Research Building, Room 618, 720 Rutland Avenue, Baltimore, Maryland 21205, USA
    Nat Med 10:S10-7. 2004
    ..There is now increased understanding of the pathways involved in protein aggregation, and some recent clues have emerged as to the molecular mechanisms of cellular toxicity. These are leading to approaches toward rational therapeutics...
  55. ncbi Mule/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the polyubiquitination of Mcl-1 and regulates apoptosis
    Qing Zhong
    Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 75390, USA
    Cell 121:1085-95. 2005
    ..The degradation of Mcl-1 can be blocked by proteasome inhibitors, suggesting a role for the ubiquitin proteasome pathway in apoptosis. Here, we demonstrate that Mcl-1 is ubiquinated at five lysines...
  56. ncbi A genomic and functional inventory of deubiquitinating enzymes
    Sebastian M B Nijman
    Division of Molecular Carcinogenesis and Center for Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Cell 123:773-86. 2005
    Posttranslational modification of proteins by the small molecule ubiquitin is a key regulatory event, and the enzymes catalyzing these modifications have been the focus of many studies...
  57. ncbi Involvement of linear polyubiquitylation of NEMO in NF-kappaB activation
    Fuminori Tokunaga
    Department of Biophysics and Biochemistry, Graduate School of Medicine and Cell Biology and Metabolism Group, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565 0871, Japan
    Nat Cell Biol 11:123-32. 2009
    ..The ubiquitin pathway is crucial in regulating the NF-kappaB pathway...
  58. pmc Building ubiquitin chains: E2 enzymes at work
    Yihong Ye
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland 20892, USA
    Nat Rev Mol Cell Biol 10:755-64. 2009
    The modification of proteins with ubiquitin chains can change their localization, activity and/or stability...
  59. pmc During muscle atrophy, thick, but not thin, filament components are degraded by MuRF1-dependent ubiquitylation
    Shenhav Cohen
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    J Cell Biol 185:1083-95. 2009
    Loss of myofibrillar proteins is a hallmark of atrophying muscle. Expression of muscle RING-finger 1 (MuRF1), a ubiquitin ligase, is markedly induced during atrophy, and MuRF1 deletion attenuates muscle wasting...
  60. pmc Linking of autophagy to ubiquitin-proteasome system is important for the regulation of endoplasmic reticulum stress and cell viability
    Wen Xing Ding
    Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15231, USA
    Am J Pathol 171:513-24. 2007
    Two major protein degradation systems exist in cells, the ubiquitin proteasome system and the autophagy machinery. Here, we investigated the functional relationship of the two systems and the underlying mechanisms...
  61. pmc SUMO-targeted ubiquitin E3 ligase RNF4 is required for the response of human cells to DNA damage
    Yili Yin
    Wellcome Trust Centre for Gene Regulation and Expression, Dundee, United Kingdom
    Genes Dev 26:1196-208. 2012
    Here we demonstrate that RNF4, a highly conserved small ubiquitin-like modifier (SUMO)-targeted ubiquitin E3 ligase, plays a critical role in the response of mammalian cells to DNA damage...
  62. pmc 53BP1 is a reader of the DNA-damage-induced H2A Lys 15 ubiquitin mark
    Amelie Fradet-Turcotte
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada
    Nature 499:50-4. 2013
    ..To accomplish its function in DNA repair, 53BP1 accumulates at DSB sites downstream of the RNF168 ubiquitin ligase...
  63. ncbi The role of ubiquitin in NF-kappaB regulatory pathways
    Brian Skaug
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9148, USA
    Annu Rev Biochem 78:769-96. 2009
    ..Particular emphasis is given to proteasome-independent functions of ubiquitin, specifically its role in the activation of protein kinase complexes and in coordination of cell survival and ..
  64. ncbi Ubiquitin: same molecule, different degradation pathways
    Michael J Clague
    Institute of Translational Medicine, University of Liverpool, UK
    Cell 143:682-5. 2010
    b>Ubiquitin is a common demoninator in the targeting of substrates to all three major protein degradation pathways in mammalian cells: the proteasome, the lysosome, and the autophagosome...
  65. ncbi The anaphase promoting complex/cyclosome: a machine designed to destroy
    Jan Michael Peters
    Research Institute of Molecular Pathology, Dr Bohr Gasse 7, A 1030 Vienna, Austria
    Nat Rev Mol Cell Biol 7:644-56. 2006
    The anaphase promoting complex/cyclosome (APC/C) is a ubiquitin ligase that has essential functions in and outside the eukaryotic cell cycle...
  66. ncbi Ubiquitin-binding domains - from structures to functions
    Ivan Dikic
    Institute of Biochemistry II and Cluster of Excellence Macromolecular Complexes, Goethe University Frankfurt, Germany
    Nat Rev Mol Cell Biol 10:659-71. 2009
    b>Ubiquitin-binding domains (UBDs) are modular elements that bind non-covalently to the protein modifier ubiquitin...
  67. ncbi Selective autophagy: ubiquitin-mediated recognition and beyond
    Claudine Kraft
    Institute of Biochemistry, ETH Zurich, Schafmattstrasse 18, CH 8093 Zurich, Switzerland
    Nat Cell Biol 12:836-41. 2010
    Eukaryotic cells use autophagy and the ubiquitin-proteasome system as their major protein degradation pathways...
  68. pmc Ubiquitin signals autophagic degradation of cytosolic proteins and peroxisomes
    Peter Kijun Kim
    Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 105:20567-74. 2008
    ..This targeting requires the ubiquitin-binding protein, p62, and is blocked by the Class III phosphatidylinositol 3-kinase (PI3K) inhibitor, 3-..
  69. pmc Ubiquitin-dependent regulation of COPII coat size and function
    Lingyan Jin
    Department of Molecular and Cell Biology, University of California at Berkeley, California 94720, USA
    Nature 482:495-500. 2012
    ..Here, we identified the ubiquitin ligase CUL3-KLHL12 as a regulator of COPII coat formation...
  70. ncbi Linear ubiquitination prevents inflammation and regulates immune signalling
    Bjorn Gerlach
    Tumour Immunology Unit, Department of Medicine, Imperial College London, W12 0NN London, UK
    Nature 471:591-6. 2011
    ..Recently linear ubiquitin chains assembled by a complex containing HOIL-1 and HOIP (also known as RBCK1 and RNF31, respectively) were ..
  71. ncbi Will the ubiquitin system furnish as many drug targets as protein kinases?
    Philip Cohen
    Sir James Black Centre, Dundee, Scotland, UK
    Cell 143:686-93. 2010
    ..In contrast, drug discovery programs that target components of the ubiquitin system have lagged behind...
  72. pmc Sequestosome 1/p62 is a polyubiquitin chain binding protein involved in ubiquitin proteasome degradation
    M Lamar Seibenhener
    Program in Cell and Molecular Biosciences, Department of Biological Sciences, Auburn University, AL 36849, USA
    Mol Cell Biol 24:8055-68. 2004
    Herein, we demonstrate that the ubiquitin-associated (UBA) domain of sequestosome 1/p62 displays a preference for binding K63-polyubiquitinated substrates...
  73. pmc Cdc48/p97 mediates UV-dependent turnover of RNA Pol II
    Rati Verma
    California Institute of Technology, Pasadena, CA 91125, USA
    Mol Cell 41:82-92. 2011
    Cdc48/p97 is an essential ATPase whose role in targeting substrates to the ubiquitin-proteasome system (UPS) remains unclear. Existing models posit that Cdc48 acts upstream of UPS receptors...
  74. ncbi HDAC6 and microtubules are required for autophagic degradation of aggregated huntingtin
    Atsushi Iwata
    Department of Biological Sciences, Bio X Program, Stanford University, Stanford, California 94305 5430, USA
    J Biol Chem 280:40282-92. 2005
    ..The ubiquitin-proteasome system protects cells against proteotoxicity by degrading soluble monomeric misfolded aggregation-..
  75. ncbi Ubiquitylation in innate and adaptive immunity
    Vijay G Bhoj
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    Nature 458:430-7. 2009
    ..Recent work has shown that several ubiquitin ligases help to prevent the immune system from attacking self tissues...
  76. ncbi The emerging complexity of protein ubiquitination
    David Komander
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge, UK
    Biochem Soc Trans 37:937-53. 2009
    ..However, the ubiquitin system is vastly more complex compared with phosphorylation...
  77. ncbi The differential modulation of USP activity by internal regulatory domains, interactors and eight ubiquitin chain types
    Alex C Faesen
    Division of Biochemistry and Center for Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Chem Biol 18:1550-61. 2011
    b>Ubiquitin-specific proteases (USPs) are papain-like isopeptidases with variable inter- and intramolecular regulatory domains...
  78. ncbi Mature ribosomes are selectively degraded upon starvation by an autophagy pathway requiring the Ubp3p/Bre5p ubiquitin protease
    Claudine Kraft
    Institute of Biochemistry, HPM, ETH Honggerberg, 8093 Zurich, Switzerland
    Nat Cell Biol 10:602-10. 2008
    Eukaryotic cells use autophagy and the ubiquitin-proteasome system (UPS) as their major protein degradation pathways...
  79. ncbi S-nitrosylated protein-disulphide isomerase links protein misfolding to neurodegeneration
    Takashi Uehara
    Center for Neuroscience and Aging, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
    Nature 441:513-7. 2006
    ..Thus, PDI prevents neurotoxicity associated with ER stress and protein misfolding, but NO blocks this protective effect in neurodegenerative disorders through the S-nitrosylation of PDI...
  80. ncbi Cellular functions of the DUBs
    Michael J Clague
    Physiological Laboratory, Institute of Translational Medicine, University of Liverpool, Crown Street, L69 3BX Liverpool, UK
    J Cell Sci 125:277-86. 2012
    ..The dynamic nature of ubiquitylation events is important for governing protein stability, maintaining ubiquitin homeostasis and controlling ubiquitin-dependent signalling pathways...
  81. pmc The Atg8 and Atg12 ubiquitin-like conjugation systems in macroautophagy. 'Protein modifications: beyond the usual suspects' review series
    Jiefei Geng
    Life Sciences Institute and Department of Molecular, Cellular and Developmental Biology, University of Michigan, Michigan 48109 2216, USA
    EMBO Rep 9:859-64. 2008
    ..Among the approximately 30 autophagy-related (Atg) genes identified so far, there are two ubiquitin-like proteins, Atg12 and Atg8...
  82. ncbi UV-induced ubiquitylation of XPC protein mediated by UV-DDB-ubiquitin ligase complex
    Kaoru Sugasawa
    Cellular Physiology Laboratory, RIKEN Discovery Research Institute, Japan Science and Technology Agency, Wako, Saitama 351 0198, Japan
    Cell 121:387-400. 2005
    ..and UV-DDB were demonstrated to interact physically, and both are polyubiquitylated by the recombinant UV-DDB-ubiquitin ligase complex...
  83. ncbi Proteolysis: from the lysosome to ubiquitin and the proteasome
    Aaron Ciechanover
    Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Efron Street, Bat Galim, Haifa 31096, Israel
    Nat Rev Mol Cell Biol 6:79-87. 2005
    ..The discovery of the ubiquitin-proteasome system resolved this enigma.
  84. ncbi SHARPIN is a component of the NF-κB-activating linear ubiquitin chain assembly complex
    Fuminori Tokunaga
    Department of Biophysics and Biochemistry, Graduate School of Medicine, Osaka University, Suita, Osaka 565 0871, Japan
    Nature 471:633-6. 2011
    ..SHARPIN shows significant similarity to HOIL-1L (also known as RBCK1), a component of linear ubiquitin chain assembly complex (LUBAC), which induces NF-κB activation through conjugation of linear polyubiquitin ..
  85. pmc Conformational selection and induced fit mechanism underlie specificity in noncovalent interactions with ubiquitin
    Tomasz Wlodarski
    Laboratory of Bioinformatics and Bioengineering, Interdisciplinary Centre for Mathematical and Computational Modeling, University of Warsaw, Zwirki i Wigury 93 02 089, Warsaw, Poland
    Proc Natl Acad Sci U S A 106:19346-51. 2009
    ..Here, we perform an extensive structural analysis of a large set of bound and unbound ubiquitin conformers and study the level of residual induced fit after conformational selection in the binding process...
  86. ncbi The tumour suppressor CYLD negatively regulates NF-kappaB signalling by deubiquitination
    Andrew Kovalenko
    Department of Biological Chemistry, The Weizmann Institute of Science, 76100 Rehovot, Israel
    Nature 424:801-5. 2003
    ..Truncations of CYLD found in cylindromatosis result in reduced enzymatic activity, indicating a link between impaired deubiquitination of CYLD substrates and human pathophysiology...
  87. ncbi CYLD is a deubiquitinating enzyme that negatively regulates NF-kappaB activation by TNFR family members
    Eirini Trompouki
    Institute of Immunology, Biomedical Sciences Research Center Alexander Fleming, 34 Alexander Fleming Street, Vari 16672, Greece
    Nature 424:793-6. 2003
    ..These results indicate that CYLD is a negative regulator of the cytokine-mediated activation of NF-kappaB that is required for appropriate cellular homeostasis of skin appendages...
  88. pmc SHARPIN forms a linear ubiquitin ligase complex regulating NF-κB activity and apoptosis
    Fumiyo Ikeda
    Frankfurt Institute for Molecular Life Sciences and Institute of Biochemistry II, Goethe University School of Medicine, Theodor Stern Kai 7, D 60590 Frankfurt, Main, Germany
    Nature 471:637-41. 2011
    SHARPIN is a ubiquitin-binding and ubiquitin-like-domain-containing protein which, when mutated in mice, results in immune system disorders and multi-organ inflammation...
  89. ncbi A proteomics approach to understanding protein ubiquitination
    Junmin Peng
    Department of Cell Biology, 240 Longwood Avenue, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Biotechnol 21:921-6. 2003
    ..We report here a proteomics approach to enrich, recover, and identify ubiquitin conjugates from Saccharomyces cerevisiae lysate...
  90. ncbi The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage
    Regina Groisman
    Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Cell 113:357-67. 2003
    ..Both complexes contain cullin 4A and Roc1 and display ubiquitin ligase activity...
  91. pmc Skp2 inhibits FOXO1 in tumor suppression through ubiquitin-mediated degradation
    Haojie Huang
    Department of Biochemistry, and Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    Proc Natl Acad Sci U S A 102:1649-54. 2005
    ..However, the ubiquitin ligase necessary for the ubiquitination of the FOXO factors and the relevance of this regulation to ..
  92. ncbi Physiological functions of the HECT family of ubiquitin ligases
    Daniela Rotin
    Program in Cell Biology, The Hospital for Sick Children, Ontario, Canada
    Nat Rev Mol Cell Biol 10:398-409. 2009
    The ubiquitylation of proteins is carried out by E1, E2 and E3 (ubiquitin ligase) enzymes, and targets them for degradation or for other cellular fates...
  93. pmc Ubiquitination of E3 ligases: self-regulation of the ubiquitin system via proteolytic and non-proteolytic mechanisms
    P De Bie
    Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Haifa, Israel
    Cell Death Differ 18:1393-402. 2011
    b>Ubiquitin modification of many cellular proteins targets them for proteasomal degradation, but in addition can also serve non-proteolytic functions...
  94. pmc The spatial and temporal organization of ubiquitin networks
    Caroline Grabbe
    Department of Molecular Biology, Umea University, Umea, Sweden
    Nat Rev Mol Cell Biol 12:295-307. 2011
    In the past decade, the diversity of signals generated by the ubiquitin system has emerged as a dominant regulator of biological processes and propagation of information in the eukaryotic cell...
  95. ncbi Constructing and decoding unconventional ubiquitin chains
    Christian Behrends
    Institute of Biochemistry II, Goethe University School of Medicine, Frankfurt, Germany
    Nat Struct Mol Biol 18:520-8. 2011
    One of the most notable discoveries in the ubiquitin system during the past decade is the extensive use of diverse chain linkages to control signaling networks...
  96. pmc OS-9 and GRP94 deliver mutant alpha1-antitrypsin to the Hrd1-SEL1L ubiquitin ligase complex for ERAD
    John C Christianson
    Department of Biological Sciences and Bio X Program, Stanford University, Lorry Lokey Bldg, 337 Campus Drive, Stanford, CA 94305, USA
    Nat Cell Biol 10:272-82. 2008
    Terminally misfolded or unassembled proteins in the early secretory pathway are degraded by a ubiquitin- and proteasome-dependent process known as ER-associated degradation (ERAD)...
  97. pmc A bacterial E3 ubiquitin ligase IpaH9.8 targets NEMO/IKKgamma to dampen the host NF-kappaB-mediated inflammatory response
    Hiroshi Ashida
    Department of Microbiology and Immunology, University of Tokyo, 4 6 1, Shirokanedai, Minato ku, Tokyo 108 8639, Japan
    Nat Cell Biol 12:66-73; sup pp 1-9. 2010
    ..IpaH9.8 interacts with NEMO/IKKgamma and ABIN-1, a ubiquitin-binding adaptor protein, promoting ABIN-1-dependent polyubiquitylation of NEMO...
  98. ncbi Mono- versus polyubiquitination: differential control of p53 fate by Mdm2
    Muyang Li
    Institute for Cancer Genetics and Department of Pathology, College of Physicians and Surgeons, Columbia University, 1150 St Nicholas Avenue, New York, NY 10032, USA
    Science 302:1972-5. 2003
    ..A p53-ubiquitin fusion protein that mimics monoubiquitinated p53 was found to accumulate in the cytoplasm in an Mdm2-independent ..
  99. ncbi Targeting the ubiquitin system in cancer therapy
    Daniela Hoeller
    Division of Medical Biochemistry, Innsbruck Medical University, Biocenter, Fritz Pregl Strasse 3, 6020 Innsbruck, Austria
    Nature 458:438-44. 2009
    The ubiquitin system is a network of proteins dedicated to the ubiquitylation of cellular targets and the subsequent control of numerous cellular functions...
  100. ncbi Recruitment of the linear ubiquitin chain assembly complex stabilizes the TNF-R1 signaling complex and is required for TNF-mediated gene induction
    Tobias L Haas
    Division of Apoptosis Regulation, German Cancer Research Center DKFZ, 69120 Heidelberg, Germany
    Mol Cell 36:831-44. 2009
    ..Together, they were shown to form a linear ubiquitin chain assembly complex (LUBAC) and to ubiquitylate NEMO...
  101. ncbi Molecular pathways of neurodegeneration in Parkinson's disease
    Ted M Dawson
    Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Science 302:819-22. 2003
    ..Dysfunction of parkin (a ubiquitin E3 ligase) and DJ-1 could contribute to these deficits...

Research Grants72

  1. Role of SAMe on UBC9 and sumolyation in liver cancer and alcoholic liver injury
    Maria Lauda Tomasi; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Posttranslational modifications mediated by ubiquitin-like proteins regulate a variety of cellular pathways...
  2. Cellular &Inflammatory Pathways in Ashtma &Allergic Diseases: From IgE to Cells
    LAWRENCE BARRY SCHWARTZ; Fiscal Year: 2012
    ..IgEs differentially affect mast cell activation in Project 3, and how Treg cells are regulated by Itch, an E3 ubiquitin ligase, in Project 4...
  3. Mechanisms of action of ghrelin in muscle and adipose tissue in cancer-related ca
    Jose M Garcia; Fiscal Year: 2013
    ..and cisplatin-induced cachexia, ghrelin will prevent muscle wasting by downregulating proteolysis through the ubiquitin-proteasome pathway...
  4. REGULATION AND FUNCTION OF STE20-RELATED PROTEIN KINASES
    Melanie H Cobb; Fiscal Year: 2012
    ..The serum- and glucocorticoid-inducible protein kinase SGK1 phosphorylates the E3 ubiquitin ligase neural precursor cell expressed, developmentally down regulated 4-2 (Nedd4-2)...
  5. Induction and maintenance of regulatory T cells
    Mitchell Kronenberg; Fiscal Year: 2013
    ..In Project 1, led by Dr. Liu, we will investigate how an E3 ubiquitin ligase, Cbl-b, stimulates Foxp3 induction, via a pathway that leads to increased activity of the transcription ..
  6. Role and Regulation of INrf2
    ANIL KUMAR JAISWAL; Fiscal Year: 2013
    ..INrf2 functions as an adaptor that interacts with Nrf2 and brings closer to ubiquitin ligase Cul3-Rbx1 for ubiquitination and degrading of Nrf2...
  7. Cell Cycle Regulation and Adult T Cell Leukemia
    Chou Zen Giam; Fiscal Year: 2013
    ..We have shown that Tax can activate the anaphase promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase that controls metaphase to anaphase transition and mitotic exit...
  8. Extracellular ubiquitin: role in myocyte apoptosis and myocardial remodeling
    Krishna Singh; Fiscal Year: 2010
    ..Using 2-dimensional gel electrophoresis followed by MALDI TOF and MS/MS, we identified ubiquitin in the conditioned media of ARVMs treated with ?-AR agonist, isoproterenol...
  9. In Vivo Function of TRAF6 As a Target of K63-Linked Polyubiquitination
    DEAN BALLARD; Fiscal Year: 2010
    ..TNFR-associated factor 6 (TRAF6), a ubiquitin (Ub)-protein ligase (E3), underpins many of the TLR-dependent immune responses to pathogen-associated molecular ..
  10. Intermediary Metabolism, Histone Acetylation, and Transcriptional Regulation
    Ales Vancura; Fiscal Year: 2013
    ..in glucose transport and metabolism caused by the failure to degrade transcriptional repressor Mth1 by the ubiquitin-proteasome pathway...
  11. IRON REGULATION OF GENE EXPRESSION
    ELIZABETH ANN LEIBOLD; Fiscal Year: 2013
    ..novel pathways and proteins regulating IRP2 function: iron-dependent proteolysis by an iron-regulated FBXL5 ubiquitin ligase and iron-independent regulation of RNA-binding activity by cyclin-dependent kinase 1 (CDK1) ..
  12. Nutrition and Anabolic Interventions in Cancer Cachexia
    Melinda Sheffield-Moore; Fiscal Year: 2013
    ..necrosis factor-? (TNF-?) enhance nuclear factor-?B (NF-?B), which in turn activates muscle proteolysis via the ubiquitin-proteasome system...
  13. Molecular Pathogenesis of MDS and CMML
    Jaroslaw P Maciejewski; Fiscal Year: 2013
    ..By sequencing the c-Cbl gene, an E3 ubiquitin ligase in this chromosomal region, a mutation involving a critical part of this gene was identified...
  14. Molecular Pathological Mechanism & Potential Therapeutics of Lafora Disease
    YAN NONE LIU; Fiscal Year: 2010
    ..they are inefficiently degraded by proteasome and are retained intracellularly as detergent-resistant ubiquitin-positive aggregates around nuclei...
  15. Role of Vimentin in Pathogenesis of CNS Inflammation
    Sheng He Huang; Fiscal Year: 2013
    ..Vim- mediated modulation of the ubiquitin proteasome system (UPS) is essential for NF-kB activation...
  16. Mechanisms of Splicing Regulation During Environmental Stress in Yeast
    Jaclyn C Greimann; Fiscal Year: 2012
    ..genes fall into only a few classes such as ribosomal protein genes, genes involved in sporulation and ubiquitin-like conjugation enzymes (Grate and Ares, 2002), suggesting a possible function of splicing in these pathways...
  17. Insulin Signaling and Metabolic Effects through CLK2 Kinase
    Pere Puigserver; Fiscal Year: 2013
    ..analysis of how insulin controls Clk2 kinase activity focusing on regulation of Clk2 protein degradation through ubiquitin ligases...
  18. MECHANISMS OF DENDRITE MORPHOGENESIS BY THE ANAPHASE-PROMOTING COMPLEX
    ALBERT HONG JAE KIM; Fiscal Year: 2013
    ..The candidate previously discovered that strikingly, major mitotic ubiquitin ligase Cdc20-Anaphase- Promoting Complex (Cdc20-APC) is required for dendrite morphogenesis in post-mitotic ..
  19. Sphingosine 1-phosphate receptors in vascular homeostasis and pathology
    TIMOTHY TUN HLA; Fiscal Year: 2012
    ..that selective subcellular targeting of S1P1R, namely, recycling between endosomes and plasma membrane or ubiquitin-based targeting to degradative organelle is an important aspect of regulation and decipher the molecular ..
  20. Prevalence and Impact of Frailty among Dialysis Patients
    Kirsten L Johansen; Fiscal Year: 2013
    ..to determine whether markers of oxidative stress are also associated with expression of proteins involved in the ubiquitin proteasome system, the major pathway of muscle catabolism...
  21. 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...
  22. Host Defense Mechanisms in Polyaromatic Hydrogen Carcinogenesis
    Craig A Elmets; Fiscal Year: 2013
    ..To test our hypothesis, we have prepared a genetic-immunization vector containing a ubiquitin-mutant ras fusion minigene sequence which provides superior proteosome targeting of the encoded protein...
  23. GILZ Regulation of ENaC
    David Pearce; Fiscal Year: 2012
    ..GILZIPs) include SGK1 (a phosphatidyl inositol-3-kinase-dependent kinase, which stimulates ENaC), Nedd4-2 (a ubiquitin ligase, which inhibits ENaC), and Raf-1 (the master regulator of the Raf-MEK-ERK signaling module, which has ..
  24. Genetic Control of Axial Patterning in Drosophila Eye
    Amit Singh; Fiscal Year: 2010
    ..L function in retinal cell fate determination and differentiation, and (iii) function of L and Cullin-4, an E3 ubiquitin ligase, in the control of ventral eye cell survival...
  25. Post-translational regulation of MLL in leukemogenesis
    ANDREW GEORGE MUNTEAN; Fiscal Year: 2013
    ..Current research identified ASB2 and an associated E3 ubiquitin ligase complex binds to the PHD fingers of MLL and promotes proteosomal dependent degradation...
  26. Post-translational regulation of MLL in leukemogenesis
    ANDREW GEORGE MUNTEAN; Fiscal Year: 2012
    ..Current research identified ASB2 and an associated E3 ubiquitin ligase complex binds to the PHD fingers of MLL and promotes proteosomal dependent degradation...
  27. HEPATIC DEGRADATION OF CYTOCHROME P450 ENZYMES
    Maria Almira Correia; Fiscal Year: 2013
    ..human liver and intestinal P450, and the EtOH-metabolizing CYP2E1 incurs ubiquitination by gp78 and CHIP E3 ubiquitin (Ub)-ligases and the 26S proteasome (UPD) which leads to their accelerated cellular disposal...
  28. The Role of hPso4 in DNA Repair and Chemotherapy Resistance
    Montaser Shaheen; Fiscal Year: 2013
    ..Since hPso4 contains U-box that displays ubiquitin E3 ligase activity, we will investigate the role of this ubiquitination in DNA repair and Histone modifications...
  29. Prevention of acute GvHD by inhibition of cdk2
    Vassiliki A Boussiotis; Fiscal Year: 2012
    ..In conjunction with cyclin E, cdk2 phosphorylates the cell cycle inhibitor p27kip1 resulting in ubiquitin-targeted degradation...
  30. Cell death regulation in proteotoxic therapy
    Wei Xing Zong; Fiscal Year: 2013
    ..This caspase-8 activation is mediated by its association with a ubiquitin-binding protein SQSTM1/p62 and an autophagy-related protein microtubule-associated protein light chain 3 (LC3)...
  31. Mechanisms of cancer initiation by TRIM32
    Molly F Kulesz-Martin; Fiscal Year: 2012
    PROJECT SUMMARY Trim32 is an E3-ubiquitin ligase and a member of a family of scaffold proteins involved in both cancer and human development...
  32. Role of sumoylation in alcoholic liver disease
    Maria Lauda Tomasi; Fiscal Year: 2013
    ..Sumoylation is often increased under oxidative stress. We recently reported that ubiquitin conjugating enzyme 9 (Ubc9), the sole E2 enzyme of sumoylation, is induced in intragastric ethanol- infusion (EI)..
  33. Negative regulation of NF-kB and inflammation by TAX1BP1
    Edward W Harhaj; Fiscal Year: 2012
    ..A20 is a ubiquitin-editing enzyme that plays an essential role in the termination of NF-kB responses triggered by TNF and LPS by ..
  34. Molecular and Cellular Mechanisms of IL-17 Signaling
    Xiaoxia Li; Fiscal Year: 2013
    ..We recently reported that Act1 is a novel bona fide U-box E3 ubiquitin ligase, whose activity is essential for IL-17-mediated signaling and inflammatory gene expression...
  35. MECHANISMS OF LIVER INJURY BY HEPATITIS C AND ALCOHOL
    Steven A Weinman; Fiscal Year: 2013
    ..These PTMs result from altered activity of upstream kinases, acetyl transferases, deacetylases, ubiquitin conjugating enzymes and deubiquitinases...
  36. Mechanisms of Ubiquitin Trafficking in Neurons
    Michael C Wooten; Fiscal Year: 2013
    ..role in autophagy the elimination of damaged mitochondria is impaired, which together with appearance of ubiquitin aggregates results in oxidative stress...
  37. C/EBP, atrogin-1, and muscle wasting
    Per Olof Hasselgren; Fiscal Year: 2009
    ..Myofibrillar proteolysis in muscle wasting is to a great extent regulated by the ubiquitin-proteasome pathway, in particular the expression and activity of the ubiquitin ligases atrogin-1 and MuRF1...
  38. Analysis of NKLAM: A Novel Gene Associated With Cellular Cytotoxicity
    Jacki Kornbluth; Fiscal Year: 2013
    ..Finally, a critical finding is that NKLAM functions as an E3 ubiquitin ligase. Ubiquitination is a key mechanism for regulating immune responses...
  39. The Role of Cks Proteins in Mammalian Meiosis
    Charles H Spruck; Fiscal Year: 2010
    ..M phase regulatory processes including: 1) activation of MPF kinase activity;2) activation of the multi-subunit ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C);3) proteolysis of cyclin B1;and 4) transcriptional ..
  40. Characterizaton of Motility Factor Receptor
    Avraham Raz; Fiscal Year: 2012
    ..that performs an additional function in the endoplasmic reticulum (ER) with an intrinsic RING finger-dependent ubiquitin protein ligase (E3) activity...
  41. 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...
  42. Dissecting the Function and Regulation of Stress-Induced SUMOylation
    ROBERT CHARLES AUGUSTINE; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): In eukaryotes, stress rapidly triggers the conjugation of small ubiquitin-related modifier (SUMO) to intracellular target proteins to alter their activity and mount a defense response...
  43. PROGESTIN AND GROWTH FACTOR CROSS-TALK IN BREAST CANCER
    CAROL ANN LANGE; Fiscal Year: 2010
    ..Paradoxically, these events are also required for nuclear export and rapid downregulation of liganded PRs by the ubiquitin- proteasome pathway...
  44. Role of Natural Killer Lytic-Associated Molecule (NKLAM) in Natural Killer Functi
    Jacki Kornbluth; Fiscal Year: 2010
    ..NKLAM is an E3 ubiquitin ligase, an enzyme involved in the process of protein ubiquitination...
  45. Training/Research Center-Bone Marrow Failure Syndromes
    Jaroslaw P Maciejewski; Fiscal Year: 2013
    ..Sequencing of this region demonstrated mutations in c-Cbl, an E3 ubiquitin ligase...
  46. Retroviral Subversion of ERAD and Intrinsic Immunity
    JAQUELIN PAGE DUDLEY; Fiscal Year: 2013
    ..The ER-associated degradation (ERAD) process identifies misfolded proteins, leading to addition of ubiquitin chains using E1, E2, and E3 enzymes...
  47. Mechanistic validation of SCF E3 ligase as a cancer and radiosensitizing target
    Yi Sun; Fiscal Year: 2013
    ..Our long-range goal is to discover a novel class of anticancer drugs that selectively target one type of E3 ubiquitin ligase, which is activated in human cancer...
  48. A Spontaneous Mouse Model of Motor Neuron Disease
    Kevin L Seburn; Fiscal Year: 2011
    ..examination of motor neuron cell bodies in the spinal cord ventral horn reveals pathology including eosin-rich, ubiquitin-positive inclusions...
  49. Mechanisms of viral proteases in coronavirus replication and pathogenesis
    Andrew D Mesecar; Fiscal Year: 2013
    ..proteases and their binding partners;and 4) Determine if mutation of the PLpro or PLP2 domain alters evasion of ubiquitin- or ISG15-dependent innate immune responses...
  50. HTLV-I Tax activates the anaphase promoting complex
    Chou Zen Giam; Fiscal Year: 2013
    ..We have shown that the Tax can activate the anaphase promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase that controls metaphase to anaphase transition and mitotic exit...
  51. Inflammatory Proteases, Ubiquitin Proteasome System, and Myocyte Death
    Abdelkarim Sabri; Fiscal Year: 2012
    ..One of the primary effectors of monitoring and degrading proteins is the Ubiquitin Proteasome System (UPS)...
  52. A novel axis regulates adipocyte plasticity
    Sean Hartig; Fiscal Year: 2013
    ..I discovered the small ubiquitin-related modifier (SUMO) E2-conjugation enzyme Ubc9 and its cognate microRNA (miR-30a) as a novel signaling loop ..
  53. CYTOSKELETAL REGULATION OF VESICLE TRANSPORT IN LIVER
    MARK A MC NIVEN; Fiscal Year: 2013
    ..Most recently, we have found that this complex can sort cargo through interactions with ubiquitin-associated proteins and is regulated by non- receptor tyrosine kinases...
  54. Testosterone Replacement Therapy in Advanced Chronic Kidney Disease
    Ralph Rabkin; Fiscal Year: 2009
    ..through androgen receptor upregulation, changes in the balance between IGF-1 and myostatin, changes in the ubiquitin-proteasome and calpain proteolytic systems, and suppression of inflammatory cytokines. Our specific aims are: 1...
  55. Mechanisms Involved in Age-Related Loss of Muscle Mass and Growth Response
    SUE CAROL BODINE; Fiscal Year: 2012
    ..2) Determine whether protein degradation pathways (ubiquitin proteasome system, calpain, lysosomal proteases) are activated to a greater extent in aged rats following ..
  56. Role of p62 in Protein Aggregation and Neurodegeneration in ALS
    Haining Zhu; Fiscal Year: 2009
    ..in this proposal) is a multifunctional protein involved in both of the two major protein degradation mechanisms: ubiquitin-proteasome system (UPS) and autophagy-lysosome pathway...
  57. Cyclin E Regulation in Normal and Neoplastic Hematopoiesis
    ALEXANDER C MINELLA; Fiscal Year: 2013
    ..The Fbw7 ubiquitin ligase is a major regulator of cyclin E activity and also controls the abundance of other important oncogenic ..
  58. Regulation of Osteoblast Function by Megakaryocytes: Key Signaling Proteins
    Melissa A Kacena; Fiscal Year: 2013
    ..the expression of the cell cycle arrest protein Retinoblastoma (Rb), and murine double minute-2 (Mdm2), an E3 ubiquitin ligase that regulates proteosome mediated degradation, are transiently decreased...
  59. Molecular probes for a vOTU from CCHFV using a fluorogenic peptide
    SCOTT DUSAN PEGAN; Fiscal Year: 2013
    ..of the Interferon type 1 immune response through cleavage of post- translational modifying proteins ubiquitin (Ub) and Ub-like interferon-simulated gene 15 (ISG15)...
  60. Rapid ischemic tolerance: Synaptic re-organization and reduced excitotoxicity
    Robert Meller; Fiscal Year: 2012
    ..Our prior studies have shown that rapid ischemic tolerance is mediated by selective protein degradation via the ubiquitin-proteasome system...
  61. Modulating calcineurin signaling pathways in muscle
    Beverly A Rothermel; Fiscal Year: 2012
    ..Specific Aim 2: To define interactions of RCAN1 isoforms with the ubiquitin/proteasome system and to test whether these contribute isoform-specific functions in the setting of ..
  62. BRCA1 and progesterone receptors in breast cancer
    Eva Y Lee; Fiscal Year: 2013
    ..whether PR ubiquitination is primed by GSK-3? phosphorylation and investigating the biological effects of ubiquitin-deficient as well as phosphorylation deficient PR on cell proliferation and refractory to BRCA1 regulation...
  63. NUCLEAR HORMONE ACTION--ROLE OF UBIQUITIN PATHWAYS
    Zafar Nawaz; Fiscal Year: 2003
    ..Recently, our laboratory and other have cloned ubiquitin-proteasome and ubiquitin-like (NEDD8, neural precursor cell-expressed developmentally down-regulated) pathway ..
  64. Quantitative Analysis of RING E3 Ubiquitin Ligases
    CHARLES M BRENNER; Fiscal Year: 2010
    RING E3 ubiquitin ligases are specific binding proteins that mediate the reaction of a ubiquitinated ubiquitin conjugating enzyme (E2-Ub) with a target protein to transfer ubiquitin from the active-site Cys of the E2 to a Lys side chain ..
  65. The meiotic role of dtopors in male Drosophila
    JOHN TOMKIEL; Fiscal Year: 2007
    unreadable] DESCRIPTION (provided by applicant): The tumor suppressor Topors is an E3-type ubiquitin and SUMO ligase that binds to a number of important cell cycle regulatory proteins, including p53, topoisomerase I, and DJ-1...
  66. TRAF6 E3 LIGASE FUNCTION IN OSTEOCLASTOGENESIS
    Bryant G Darnay; Fiscal Year: 2010
    ..the N-terminal RING domain of TRAF6 is required for its ability to signal, most likely by functioning as an E3 ubiquitin ligase, which together with the ubiquitin conjugating enzyme complex Ubc13/Uev1A catalyzes the synthesis of a ..
  67. Roles of ubiquitin protein ligases in endocytosis
    Linda Hicke; Fiscal Year: 2005
    The ubiquitination of many cell surface regulatory proteins is critical for their downregulation because ubiquitin signals control internalization and sorting of proteins in the endocytic pathway...
  68. STRUCTURE AND FUNCTION OF SV40 NON-VIRION PROTEINS
    David Livingston; Fiscal Year: 2007
    ..TAD-C domain of hypoxia -inducing factor and thereby act as anti-tumor agents; 3) to determine whether the E3B4 ubiquitin ligase function of p300/CBP represents a useful anti-cancer therapeutic target in MDM2 overexpressing human ..
  69. The Role of Ubiquitination on TBK1 Function
    Roosevelt Boursiquot; Fiscal Year: 2010
    ..During this process, the ubiquitin machinery covalently links either ubiquitin monomers or polymeric chains to a lysine residue on the peptide of ..
  70. Capture of Ubiquitin Conjugation and Deconjugation Enzyme Substrates
    Robert Cohen; Fiscal Year: 2010
    ..Nowhere has this problem been more evident than with ubiquitin conjugation (E3 ubiquitin ligase) and deubiquitination (DUB) enzymes...
  71. Luciferase Screen for MDM2 E3 Ligase Inhibitors
    Brent Stockwell; Fiscal Year: 2007
    ..The E3 ligases are involved in regulating other proteins by covalent ligation to the 76 amino acid protein ubiquitin. This post-translational modification can result in altered conformation, altered activity, or degradation of ..
  72. Regulation of Cellular Growth and Division by Ubiquitin-Mediated Proteolysis
    JENNIFER BENANTI; Fiscal Year: 2009
    The cell division cycle is orchestrated by the timed synthesis and subsequent ubiquitin-mediated proteolysis of key regulatory proteins...