UBC

Summary

Gene Symbol: UBC
Description: ubiquitin C
Alias: HMG20, polyubiquitin-C
Species: human

Top Publications

  1. pmc Activation of autophagy by inflammatory signals limits IL-1β production by targeting ubiquitinated inflammasomes for destruction
    Chong Shan Shi
    B Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, Maryland, USA
    Nat Immunol 13:255-63. 2012
  2. 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
  3. doi PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1
    Sven Geisler
    Laboratory of Functional Neurogenetics, Otfried Muller Strasse 27, 72076 Tubingen, Germany
    Nat Cell Biol 12:119-31. 2010
  4. 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
  5. doi A Cullin3-KLHL20 Ubiquitin ligase-dependent pathway targets PML to potentiate HIF-1 signaling and prostate cancer progression
    Wei Chien Yuan
    Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
    Cancer Cell 20:214-28. 2011
  6. pmc PINK1 is activated by mitochondrial membrane potential depolarization and stimulates Parkin E3 ligase activity by phosphorylating Serine 65
    Chandana Kondapalli
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
    Open Biol 2:120080. 2012
  7. pmc Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2
    Akira Kobayashi
    Center for Tsukuba Advanced Research Alliance, Institute of Basic Medical Sciences, and JST ERATO Environmental Response Project, University of Tsukuba, Tsukuba 305 8575, Japan
    Mol Cell Biol 24:7130-9. 2004
  8. pmc The E3 ligase TRAF6 regulates Akt ubiquitination and activation
    Wei Lei Yang
    Department of Molecular and Cellular Oncology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Science 325:1134-8. 2009
  9. 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
  10. doi The emerging complexity of protein ubiquitination
    David Komander
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge, UK
    Biochem Soc Trans 37:937-53. 2009

Research Grants

  1. ATP-Ubiquitin Dependent Proteolysis
    Arthur L Haas; Fiscal Year: 2011
  2. Yousef Abu-Amer; Fiscal Year: 2016
  3. Ali Syed Arbab; Fiscal Year: 2014
  4. Cynthia A Lemere; Fiscal Year: 2014
  5. Analysis of ubiquitination enzymes in C. elegans
    Lynn Boyd; Fiscal Year: 2009
  6. Transgenic rat overexpressing miR-15/16 cluster:functional implications in develo
    Junming Yue; Fiscal Year: 2010
  7. UBIQUITIN DEFICIENCY IN AGING AND NEURODEGENERATION
    Ron Kopito; Fiscal Year: 2006
  8. Adenosine, Toll-Like Receptors and Angiogenesis
    Samuel Joseph Leibovich; Fiscal Year: 2011
  9. Cerebellar Microcircuits: Organization &Development
    Marco Martina; Fiscal Year: 2012
  10. Carolina Borges-Merjane; Fiscal Year: 2014

Detail Information

Publications426 found, 100 shown here

  1. pmc Activation of autophagy by inflammatory signals limits IL-1β production by targeting ubiquitinated inflammasomes for destruction
    Chong Shan Shi
    B Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, Maryland, USA
    Nat Immunol 13:255-63. 2012
    ..Our data indicate that autophagy accompanies inflammasome activation to temper inflammation by eliminating active inflammasomes...
  2. 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
    ..We also provide an example of a protein containing separate ubiquitin ligase and DUB domains, both of which participate in mediating a distinct regulatory effect...
  3. doi PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1
    Sven Geisler
    Laboratory of Functional Neurogenetics, Otfried Muller Strasse 27, 72076 Tubingen, Germany
    Nat Cell Biol 12:119-31. 2010
    ..Thus, our data provide functional links between PINK1, Parkin and the selective autophagy of mitochondria, which is implicated in the pathogenesis of Parkinson's disease...
  4. 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
    ..Our results indicate that Ub-binding domains of Y-family polymerases play crucial regulatory roles in TLS...
  5. doi A Cullin3-KLHL20 Ubiquitin ligase-dependent pathway targets PML to potentiate HIF-1 signaling and prostate cancer progression
    Wei Chien Yuan
    Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
    Cancer Cell 20:214-28. 2011
    ..Our study indicates that the KLHL20-mediated PML degradation and HIF-1α autoregulation play key roles in tumor progression...
  6. pmc PINK1 is activated by mitochondrial membrane potential depolarization and stimulates Parkin E3 ligase activity by phosphorylating Serine 65
    Chandana Kondapalli
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
    Open Biol 2:120080. 2012
    ..Our findings also suggest that small molecule activators of Parkin that mimic the effect of PINK1 phosphorylation may confer therapeutic benefit for PD...
  7. pmc Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2
    Akira Kobayashi
    Center for Tsukuba Advanced Research Alliance, Institute of Basic Medical Sciences, and JST ERATO Environmental Response Project, University of Tsukuba, Tsukuba 305 8575, Japan
    Mol Cell Biol 24:7130-9. 2004
    ..To our knowledge, Nrf2 and Keap1 are the first reported mammalian substrate and adaptor, respectively, of the Cul3-based E3 ligase system...
  8. pmc The E3 ligase TRAF6 regulates Akt ubiquitination and activation
    Wei Lei Yang
    Department of Molecular and Cellular Oncology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Science 325:1134-8. 2009
    ..Thus, Akt ubiquitination is an important step for oncogenic Akt activation...
  9. 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
    ..Thus, Mule is a unique BH3-containing E3 ubiquitin ligase apical to Bcl-2 family proteins during DNA damage-induced apoptosis...
  10. doi The emerging complexity of protein ubiquitination
    David Komander
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge, UK
    Biochem Soc Trans 37:937-53. 2009
    ..For example, ubiquitination may have important allosteric roles in protein regulation that are currently not appreciated...
  11. ncbi Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53
    R Honda
    School of Life Science, Tokyo University of Pharmacy and Life Science, Japan
    FEBS Lett 420:25-7. 1997
    ..These data suggest that the MDM2 protein, which is induced by p53, functions as a ubiquitin ligase, E3, in human papillomavirus-uninfected cells which do not have E6 protein...
  12. 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...
  13. doi T-cell differentiation factor CBF-β regulates HIV-1 Vif-mediated evasion of host restriction
    Wenyan Zhang
    First Hospital of Jilin University, Institute of Virology and AIDS Research, Changchun, Jilin Province 130021, China
    Nature 481:376-9. 2011
    ..Considering the importance of the interaction between Vif and CBF-β, disrupting this interaction represents an attractive pharmacological intervention against HIV-1...
  14. ncbi TAB2 and TAB3 activate the NF-kappaB pathway through binding to polyubiquitin chains
    Atsuhiro Kanayama
    Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    Mol Cell 15:535-48. 2004
    ..These results indicate that polyubiquitin binding domains represent a new class of signaling domains that regulate protein kinase activity through a nonproteolytic mechanism...
  15. ncbi Activation of IKK by TNFalpha requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO
    Chee Kwee Ea
    Howard Hughes Medical Institute, Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    Mol Cell 22:245-57. 2006
    ..These results reveal the biochemical mechanism underlying the essential signaling function of NEMO and provide direct evidence that signal-induced site-specific ubiquitination of RIP1 is required for IKK activation...
  16. pmc Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex
    Donna D Zhang
    Department of Biochemistry, University of Missouri Columbia, M121 Medical Sciences Building, Columbia, MO 65212, USA
    Mol Cell Biol 24:10941-53. 2004
    ....
  17. ncbi Suppressor of cytokine signaling 1 negatively regulates Toll-like receptor signaling by mediating Mal degradation
    Ashley Mansell
    Centre for Functional Genomics and Human Disease, Monash Institute of Medical Research, Monash University, Melbourne, Victoria, Australia
    Nat Immunol 7:148-55. 2006
    ..The transient activation of Mal and subsequent SOCS-1-mediated degradation is a rapid and selective means of limiting primary innate immune response...
  18. 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
    ..The critical function of this deubiquitinating enzyme in the restriction of TLR signals emphasizes the importance of the regulation of ubiquitin conjugation in innate immune cells...
  19. pmc PINK1 drives Parkin self-association and HECT-like E3 activity upstream of mitochondrial binding
    Michael Lazarou
    Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 200:163-72. 2013
    ..Self-association occurred independent of ubiquitination activity through the RING-between-RING domain, providing mechanistic insight into how PINK1 activates Parkin...
  20. pmc Structure of the human Parkin ligase domain in an autoinhibited state
    Tobias Wauer
    Division of Protein and Nucleic Acid Chemistry, Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
    EMBO J 32:2099-112. 2013
    ..Opening of intra-domain interfaces activates Parkin, and enables Ub-based suicide probes to modify Cys431. The structure further reveals a putative phospho-peptide docking site in the UPD, and explains many PD-causing mutations. ..
  21. ncbi Loss of the cylindromatosis tumour suppressor inhibits apoptosis by activating NF-kappaB
    Thijn R Brummelkamp
    Division of Molecular Carcinogenesis and Center for Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Nature 424:797-801. 2003
    ..We show that this effect can be relieved by aspirin derivatives that inhibit NF-kappaB activity, which suggests a therapeutic intervention strategy to restore growth control in patients suffering from familial cylindromatosis...
  22. ncbi Ubiquitin ligase activity and tyrosine phosphorylation underlie suppression of growth factor signaling by c-Cbl/Sli-1
    G Levkowitz
    Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel
    Mol Cell 4:1029-40. 1999
    ..Our study identifies Cbl proteins as components of the ubiquitin ligation machinery and implies that they similarly suppress many other signaling pathways...
  23. ncbi Inhibition of MDM2-mediated p53 ubiquitination and degradation by ribosomal protein L5
    Mu Shui Dai
    Department of Biochemistry and Molecular Biology, School of Medicine, Oregon Health and Science University, Portland, Oregon 97201, USA
    J Biol Chem 279:44475-82. 2004
    ..We propose that the MDM2-L5-L11-L23 complex functions to inhibit MDM2-mediated p53 ubiquitination and thus activates p53...
  24. pmc A critical role of RICK/RIP2 polyubiquitination in Nod-induced NF-kappaB activation
    Mizuho Hasegawa
    Department of Pathology, The University of Michigan Medical School, Ann Arbor, MI 48109, USA
    EMBO J 27:373-83. 2008
    ..Thus, RICK polyubiquitination links TAK1 to IKK complexes, a critical step in Nod1/Nod2-mediated NF-kappaB activation...
  25. pmc Ubiquitin ligase Nedd4L targets activated Smad2/3 to limit TGF-beta signaling
    Sheng Gao
    Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Mol Cell 36:457-68. 2009
    ..Previously identified as a regulator of renal sodium channels, Nedd4L is shown here to play a broader role as a general modulator of Smad turnover during TGF-beta signal transduction...
  26. doi Focal-adhesion targeting links caveolin-1 to a Rac1-degradation pathway
    Micha Nethe
    Department of Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands
    J Cell Sci 123:1948-58. 2010
    ..These data extend the canonical model of Rac1 inactivation and uncover Cav1-regulated polyubiquitylation as an additional mechanism to control Rac1 signalling...
  27. pmc Oxidized DJ-1 interacts with the mitochondrial protein BCL-XL
    Haigang Ren
    Laboratory of Molecular Neuropathology, Key Laboratory of Brain Functions and Diseases and School of Life Sciences, University of Science and Technology of China, Chinese Academy of Sciences, Hefei, Anhui 230027, People s Republic of China and
    J Biol Chem 286:35308-17. 2011
    ..These data suggest that DJ-1 protects cells against UVB-induced cell death dependent on its oxidation and its association with mitochondrial Bcl-X(L)...
  28. ncbi Structure of ubiquitin refined at 1.8 A resolution
    S Vijay-Kumar
    J Mol Biol 194:531-44. 1987
    ..The molecule features a number of unusual secondary structural features, including a parallel G1 beta-bulge, two reverse Asx turns, and a symmetrical hydrogen-bonding region that involves the two helices and two of the reverse turns...
  29. doi 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
    ..These results demonstrate that poly-SUMO chains can act as discrete signals from mono-SUMOylation, in this case targeting a poly-SUMOylated substrate for ubiquitin-mediated proteolysis...
  30. doi Ubiquitination of alpha 5 beta 1 integrin controls fibroblast migration through lysosomal degradation of fibronectin-integrin complexes
    Viola Hélène Lobert
    Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, 0316 Oslo, Norway
    Dev Cell 19:148-59. 2010
    ..Fibronectin and alpha 5 beta 1 integrin therefore are trafficked to lysosomes in a similar way to growth factors and their receptors...
  31. pmc The ubiquitin-editing enzyme A20 restricts nucleotide-binding oligomerization domain containing 2-triggered signals
    Osamu Hitotsumatsu
    UCSF Colitis Center, Gastroenterology Division, Department of Medicine, Program in Biomedical Sciences, University of California at San Francisco, San Francisco, CA 94143 0538, USA
    Immunity 28:381-90. 2008
    ..These findings indicate that A20 directly restricts NOD2 induced signals in vitro and in vivo, and provide new insights into how these signals are physiologically restricted...
  32. ncbi CHIP and Hsp70 regulate tau ubiquitination, degradation and aggregation
    Leonard Petrucelli
    Mayo Clinic, Jacksonville, FL 32224, USA
    Hum Mol Genet 13:703-14. 2004
    ..Hsp70/CHIP may therefore play an important role in the pathogenesis of tauopathies and also represents a potential therapeutic target...
  33. doi 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
    ..Finally, we demonstrate that sustained stability of the TNF-RSC requires LUBAC's enzymatic activity, thereby adding a third form of ubiquitin linkage to the triggering of TNF signaling by the TNF-RSC...
  34. pmc A ubiquitin-binding protein, FAAP20, links RNF8-mediated ubiquitination to the Fanconi anemia DNA repair network
    Zhijiang Yan
    Laboratory of Genetics, National Institute of Aging, National Institutes of Health, Baltimore, MD 21224, USA
    Mol Cell 47:61-75. 2012
    ..Thus, the RNF8-FAAP20 ubiquitin cascade is critical for recruiting FA core complex to ICLs and for normal function of the FA network...
  35. pmc Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress
    Donna D Zhang
    Department of Biochemistry, University of Missouri Columbia, Columbia, MO 65212, USA
    Mol Cell Biol 23:8137-51. 2003
    ..We propose that Keap1 is a component of a novel E3 ubiquitin ligase complex that is specifically targeted for inhibition by both chemopreventive agents and oxidative stress...
  36. pmc Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite development
    Hiroshi Kawabe
    Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Gottingen, Germany
    Neuron 65:358-72. 2010
    ..We conclude that a Nedd4-1/Rap2A/TNIK signaling pathway regulates neurite growth and arborization in mammalian neurons...
  37. pmc Itch E3 ubiquitin ligase regulates large tumor suppressor 1 stability [corrected]
    King Ching Ho
    Department of Pathology and Molecular Medicine, Queen s University, Kingston, ON, Canada K7L 3N6
    Proc Natl Acad Sci U S A 108:4870-5. 2011
    ..Taking these data together, our study identifies E3 ubiquitin ligase Itch as a unique negative regulator of LATS1 and presents a possibility of targeting LATS1/Itch interaction as a therapeutic strategy in cancer...
  38. ncbi Multiple monoubiquitination of RTKs is sufficient for their endocytosis and degradation
    Kaisa Haglund
    Ludwig Institute for Cancer Research, Husargatan 3, SE 75 124 Uppsala, Sweden
    Nat Cell Biol 5:461-6. 2003
    ..Thus, monoubiquitination is the principal signal responsible for the movement of RTKs from the plasma membrane to the lysosome...
  39. ncbi Crystal structure of the ubiquitin binding domains of rabex-5 reveals two modes of interaction with ubiquitin
    Lorenza Penengo
    IFOM, the FIRC Institute for Molecular Oncology Foundation, Via Adamello 16, 20139 Milan, Italy
    Cell 124:1183-95. 2006
    ..The two binding surfaces allow Ub to interact simultaneously with different UBDs, thus opening new perspectives in Ub-mediated signaling...
  40. pmc An unbiased screen identifies DEP-1 tumor suppressor as a phosphatase controlling EGFR endocytosis
    Gabi Tarcic
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel
    Curr Biol 19:1788-98. 2009
    ..Because hyperphosphorylation of EGFR is involved in oncogenic pathways, we performed an unbiased screen of small interfering RNA (siRNA) oligonucleotides targeting all human tyrosine phosphatases...
  41. pmc Wolfram syndrome 1 gene negatively regulates ER stress signaling in rodent and human cells
    Sonya G Fonseca
    Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA 01605 2324, USA
    J Clin Invest 120:744-55. 2010
    ..These results reveal a role for WFS1 in the negative regulation of ER stress signaling and in the pathogenesis of diseases involving chronic, unresolvable ER stress, such as pancreatic beta cell death in diabetes...
  42. pmc Lys11-linked ubiquitin chains adopt compact conformations and are preferentially hydrolyzed by the deubiquitinase Cezanne
    Anja Bremm
    Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
    Nat Struct Mol Biol 17:939-47. 2010
    ..Our data highlight the intrinsic specificity of the ubiquitin system that extends to Lys11-linked chains and emphasize that differentially linked polyubiquitin chains must be regarded as independent post-translational modifications...
  43. pmc Disrupted-in-schizophrenia 1 (DISC1) plays essential roles in mitochondria in collaboration with Mitofilin
    Young Un Park
    Division of Molecular and Life Science, Department of Life Science, Biotechnology Research Center, Pohang University of Science and Technology, Pohang 790 784, Korea
    Proc Natl Acad Sci U S A 107:17785-90. 2010
    ..According to these results, we propose that DISC1 plays essential roles for mitochondrial function in collaboration with a mitochondrial interacting partner, Mitofilin...
  44. ncbi Smurf1 interacts with transforming growth factor-beta type I receptor through Smad7 and induces receptor degradation
    T Ebisawa
    Department of Biochemistry, The Cancer Institute of the Japanese Foundation for Cancer Research, and Research for the Future Program, the Japan Society for the Promotion of Science, 1 37 1 Kami Ikebukuro, Toshima ku, Tokyo 170 8455, Japan
    J Biol Chem 276:12477-80. 2001
    ..These results thus reveal a novel function of Smad7, i.e. induction of degradation of TbetaR-I through recruitment of an E3 ligase to the receptor...
  45. pmc A ubiquitin ligase complex assembles linear polyubiquitin chains
    Takayoshi Kirisako
    Department of Molecular Cell Biology, Graduate School of Medicine, Osaka City University, Osaka, Japan
    EMBO J 25:4877-87. 2006
    ..Moreover, the complex regulates the stability of Ub-GFP (a GFP fusion protein with an N-terminal ubiquitin). The linear polyubiquitin chain generated post-translationally may function as a new modulator of proteins...
  46. ncbi DUBA: a deubiquitinase that regulates type I interferon production
    Nobuhiko Kayagaki
    Department of Physiological Chemistry, Genentech, South San Francisco, CA 94080, USA
    Science 318:1628-32. 2007
    ..A discrete ubiquitin interaction motif within DUBA was required for efficient deubiquitination of TRAF3 and optimal suppression of IFN-I. Our data identify DUBA as a negative regulator of innate immune responses...
  47. pmc Nedd4 mediates agonist-dependent ubiquitination, lysosomal targeting, and degradation of the beta2-adrenergic receptor
    Sudha K Shenoy
    Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 283:22166-76. 2008
    ..Collectively, our findings indicate that the degradative fate of the beta(2)AR in the lysosomal compartments is dependent upon beta-arrestin2-mediated recruitment of Nedd4 to the activated receptor and Nedd4-catalyzed ubiquitination...
  48. doi The E3 ligase Itch negatively regulates inflammatory signaling pathways by controlling the function of the ubiquitin-editing enzyme A20
    Noula Shembade
    Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami, Miller School of Medicine, Miami, Florida 33136, USA
    Nat Immunol 9:254-62. 2008
    ..Thus, our studies show a previously unappreciated complexity of A20 substrate recognition and inactivation whereby TAX1BP1 and Itch function as essential subunits of an A20 ubiquitin-editing complex...
  49. pmc The deubiquitinating enzyme ataxin-3, a polyglutamine disease protein, edits Lys63 linkages in mixed linkage ubiquitin chains
    Brett J Winborn
    Department of Neurology, University of Michigan, Ann Arbor, Michigan 48108, USA
    J Biol Chem 283:26436-43. 2008
    ..These findings establish ataxin-3 as a novel DUB that edits topologically complex chains...
  50. doi Specific recognition of linear ubiquitin chains by NEMO is important for NF-kappaB activation
    Simin Rahighi
    Structural Biology Research Center, Photon Factory, Institute of Materials Structure Science, High Energy Accelerator Research Organization KEK, Tsukuba, Ibaraki, Japan
    Cell 136:1098-109. 2009
    ....
  51. pmc Herpes simplex virus type 1 immediate-early protein ICP0 and is isolated RING finger domain act as ubiquitin E3 ligases in vitro
    Chris Boutell
    Medical Research Council Virology Unit, Glasgow G11 5JR, Scotland, United Kingdom
    J Virol 76:841-50. 2002
    ..We conclude that ICP0 has the potential to act as an E3 ubiquitin ligase during viral infection and to target specific cellular proteins for destruction by the 26S proteasome...
  52. ncbi RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO
    Carsten Hoege
    Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18a, 82152 Martinsried, Germany
    Nature 419:135-41. 2002
    ..We demonstrate that these modifications differentially affect resistance to DNA damage, and that damage-induced PCNA ubiquitination is elementary for DNA repair and occurs at the same conserved residue in yeast and humans...
  53. 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
    ..Altogether, our results support the hypothesis that p62 may act as a critical ubiquitin chain-targeting factor that shuttles substrates for proteasomal degradation...
  54. pmc The ubiquitin-protein ligase Itch regulates p73 stability
    Mario Rossi
    Department of Biology, University of Rome Tor Vergata, Rome, Italy
    EMBO J 24:836-48. 2005
    ..In conclusion, we have identified a key mechanism in the control of p73 protein levels both in normal as well as in stress conditions...
  55. doi Structural basis for specific cleavage of Lys 63-linked polyubiquitin chains
    Yusuke Sato
    Structural Biology Laboratory, Life Science Division, Synchrotron Radiation Research Organization and Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113 0032, Japan
    Nature 455:358-62. 2008
    ..This is the first reported structure of a DUB in complex with an isopeptide-linked ubiquitin chain, which reveals the mechanism for Lys 63-linkage-specific deubiquitination by AMSH family members...
  56. doi The deubiquitinating enzyme USP26 is a regulator of androgen receptor signaling
    Annette M G Dirac
    The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX Netherlands
    Mol Cancer Res 8:844-54. 2010
    ..Our data suggest that USP26 assembles with AR and other cofactors in subnuclear foci, and serves to counteract hormone-induced AR ubiquitination, thereby contributing to the regulation of AR transcriptional activity...
  57. pmc A ubiquitin-like domain recruits an oligomeric chaperone to a retrotranslocation complex in endoplasmic reticulum-associated degradation
    Yue Xu
    Laboratory of Molecular Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 288:18068-76. 2013
    ..We propose that simultaneous association with multiple ERAD factors helps to anchor a disordered chaperone oligomer to the site of retrotranslocation to prevent protein aggregation in ERAD. ..
  58. pmc HIV-1 viral infectivity factor interacts with TP53 to induce G2 cell cycle arrest and positively regulate viral replication
    Taisuke Izumi
    Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Sakyo ku, Kyoto 606 8507, Japan
    Proc Natl Acad Sci U S A 107:20798-803. 2010
    ..This report demonstrates the molecular mechanisms and the biological significance of Vif-mediated G2 cell cycle arrest for HIV-1 infection...
  59. pmc Cullin-4A·DNA damage-binding protein 1 E3 ligase complex targets tumor suppressor RASSF1A for degradation during mitosis
    Lingyan Jiang
    Department of Pharmacology, State University of New York, Upstate Medical University, Syracuse, New York 13210, USA
    J Biol Chem 286:6971-8. 2011
    ..Thus, our present study demonstrates that the CUL4A·DDB1 E3 complex is important for regulation of RASSF1A during mitosis, and it may contribute to inactivation of RASSF1A and promoting cell cycle progression...
  60. pmc NLRP4 negatively regulates type I interferon signaling by targeting the kinase TBK1 for degradation via the ubiquitin ligase DTX4
    Jun Cui
    The Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA
    Nat Immunol 13:387-95. 2012
    ..Our results identify a previously unrecognized role for NLRP4 in the regulation of type I interferon signaling and provide molecular insight into the mechanisms by which NLRP4-DTX4 targets TBK1 for degradation...
  61. pmc von Hippel-Lindau protein binds hyperphosphorylated large subunit of RNA polymerase II through a proline hydroxylation motif and targets it for ubiquitination
    Anna V Kuznetsova
    Department of Molecular and Cellular Physiology, Children s Hospital Research Foundation, University of Cincinnati College of Medicine, Cincinnati, OH 45267 0576, USA
    Proc Natl Acad Sci U S A 100:2706-11. 2003
    ..This interaction is regulated by UV radiation...
  62. ncbi Balancing BMP signaling through integrated inputs into the Smad1 linker
    Gopal Sapkota
    Cancer Biology and Genetics Program, Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Mol Cell 25:441-54. 2007
    ..The interplay between linker phosphorylation, Smurf-dependent ubiquitination, and nucleoporin exclusion enables regulation of BMP action by diverse signals and biological contexts...
  63. pmc Parkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex promoting unfolded protein degradation
    Hui Xiong
    Burnham Institute for Medical Research, 10901 N Torrey Pines Road, La Jolla, CA 92037, USA
    J Clin Invest 119:650-60. 2009
    ....
  64. pmc HIV-1 Vpr loads uracil DNA glycosylase-2 onto DCAF1, a substrate recognition subunit of a cullin 4A-ring E3 ubiquitin ligase for proteasome-dependent degradation
    Jinwoo Ahn
    Department of Structural Biology, University of Pittsburgh School of Medicine and Cancer Institute, Pittsburgh, Pennsylvania 15260, USA
    J Biol Chem 285:37333-41. 2010
    ..Taken together, our results show that the CRL4(DCAF1) E3 ubiquitin ligase can be subverted by Vpr to target UNG2 for degradation...
  65. ncbi The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes
    Lijun Sun
    Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    Mol Cell 14:289-301. 2004
    ..These results reveal an oligomerization --> ubiquitination --> phosphorylation cascade that culminates in NF-kappaB activation in T lymphocytes...
  66. pmc BTB protein Keap1 targets antioxidant transcription factor Nrf2 for ubiquitination by the Cullin 3-Roc1 ligase
    Manabu Furukawa
    Lineberger Comprehensive Cancer Center, Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7295, USA
    Mol Cell Biol 25:162-71. 2005
    ..These results may reconcile previously observed cytoplasmic sequestration of NRF2 by KEAP1 and suggest a possible regulatory step between KEAP1-NRF2 binding and NRF2 degradation...
  67. pmc Molecular discrimination of structurally equivalent Lys 63-linked and linear polyubiquitin chains
    David Komander
    Division of Protein and Nucleic Acid Chemistry, Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK
    EMBO Rep 10:466-73. 2009
    ..Our results highlight remarkable specificity determinants within the ubiquitin system...
  68. pmc USP10 regulates p53 localization and stability by deubiquitinating p53
    Jian Yuan
    Division of Oncology Research, Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA
    Cell 140:384-96. 2010
    ..These findings reveal USP10 to be a novel regulator of p53, providing an alternative mechanism of p53 inhibition in cancers with wild-type p53...
  69. doi 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
    ..USPs can hydrolyze all linkages and show modest Ub-chain preferences, although some show a lack of activity toward linear di-Ub. This comprehensive kinetic analysis highlights the variability within the USP family...
  70. pmc Fanconi anemia (FA) binding protein FAAP20 stabilizes FA complementation group A (FANCA) and participates in interstrand cross-link repair
    Justin Wai Chung Leung
    Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 109:4491-6. 2012
    ..Taking these data together, our study indicates that FAAP20 is an important player involved in the FA pathway...
  71. ncbi The F-box protein Skp2 participates in c-Myc proteosomal degradation and acts as a cofactor for c-Myc-regulated transcription
    Natalie von der Lehr
    Department of Plant Biology and Forest Genetics, Swedish University of Agricultural Sciences, 750 07 Uppsala, Sweden
    Mol Cell 11:1189-200. 2003
    ..The results suggest that Skp2 is a transcriptional cofactor for c-Myc and indicates a close relationship between transcription activation and transcription factor ubiquitination...
  72. ncbi Negative regulation of transforming growth factor-beta (TGF-beta) signaling by WW domain-containing protein 1 (WWP1)
    Akiyoshi Komuro
    Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 0033, Japan
    Oncogene 23:6914-23. 2004
    ..Importantly, WWP1 and Smurfs were expressed in distinct patterns in human tissues and carcinoma cell lines, suggesting unique pathophysiological roles of WWP1 and Smurfs...
  73. ncbi Sequential quality-control checkpoints triage misfolded cystic fibrosis transmembrane conductance regulator
    J Michael Younger
    Department of Cell and Developmental Biology, UNC Chapel Hill School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA
    Cell 126:571-82. 2006
    ..Thus, the RMA1 and CHIP E3 ubiquitin ligases act sequentially in ER membrane and cytosol to monitor the folding status of CFTR and CFTR Delta F508...
  74. pmc The human T-cell leukemia virus type 1 Tax oncoprotein requires the ubiquitin-conjugating enzyme Ubc13 for NF-kappaB activation
    Noula Shembade
    Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami, Miller School of Medicine, 1550 NW 10 Avenue, Miami, FL 33136, USA
    J Virol 81:13735-42. 2007
    ..Collectively, our results reveal that Ubc13 is essential for Tax ubiquitination, its interaction with NEMO, and Tax-mediated NF-kappaB activation...
  75. pmc Efficient protection and isolation of ubiquitylated proteins using tandem ubiquitin-binding entities
    Roland Hjerpe
    Proteomics Unit, CIC bioGUNE, CIBERehd, Bizkaia Technology Park, Building 801A, Derio 48160, Spain
    EMBO Rep 10:1250-8. 2009
    ....
  76. pmc Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2
    Sergio E Alvarez
    Department of Biochemistry and Molecular Biology and the Massey Cancer Center, Virginia Commonwealth University School of Medicine, 1101 E Marshall Street, Richmond, Virginia 23298, USA
    Nature 465:1084-8. 2010
    ..These results also highlight the key role of SphK1 and its product S1P in TNF-alpha signalling and the canonical NF-kappaB activation pathway important in inflammatory, antiapoptotic and immune processes...
  77. pmc Parkin mono-ubiquitinates Bcl-2 and regulates autophagy
    Dong Chen
    Laboratory of Molecular Neuropathology, School of Life Sciences, University of Science and Technology of China, Chinese Academy of Sciences, Hefei, Anhui 230027, China
    J Biol Chem 285:38214-23. 2010
    ..Moreover, overexpression of parkin enhances the interactions between Bcl-2 and Beclin 1. Our results provide evidence that parkin mono-ubiquitinates Bcl-2 and regulates autophagy via Bcl-2...
  78. pmc The mechanism of linkage-specific ubiquitin chain elongation by a single-subunit E2
    Katherine E Wickliffe
    Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
    Cell 144:769-81. 2011
    ..Our studies suggest that monomeric E2s promote linkage-specific ubiquitin chain formation through substrate-assisted catalysis...
  79. pmc Reconstitution of the RIG-I pathway reveals a signaling role of unanchored polyubiquitin chains in innate immunity
    Wenwen Zeng
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9148, USA
    Cell 141:315-30. 2010
    ..Our results delineate the mechanism of RIG-I activation, identify CARD domains as a ubiquitin sensor, and demonstrate that unanchored K63-polyubiquitin chains are signaling molecules in antiviral innate immunity...
  80. pmc Serine-threonine ubiquitination mediates downregulation of BST-2/tetherin and relief of restricted virion release by HIV-1 Vpu
    Andrey A Tokarev
    Department of Medicine University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0679, USA
    J Virol 85:51-63. 2011
    ..Serine-threonine ubiquitination of BST-2 is likely part of the mechanism by which Vpu counteracts innate defenses...
  81. ncbi Bcl10 activates the NF-kappaB pathway through ubiquitination of NEMO
    Honglin Zhou
    Department of Molecular Oncology, Genentech Inc 1 DNA Way, South San Francisco, California 94080, USA
    Nature 427:167-71. 2004
    ..Thus, the adaptor protein Bcl10 promotes activation of NF-kappaB transcription factors through paracaspase- and UBC13-dependent ubiquitination of NEMO...
  82. pmc A critical role for FBXW8 and MAPK in cyclin D1 degradation and cancer cell proliferation
    Hiroshi Okabe
    Department of Pathology, School of Medicine, University of California San Francisco, San Francisco, California, United States of America UCSF Comprehensive Cancer Center, School of Medicine, University of California San Francisco, San Francisco, California, United States of America
    PLoS ONE 1:e128. 2006
    ..Thus, FBXW8 plays an essential role in cancer cell proliferation through proteolysis of cyclin D1. It may present new opportunities to develop therapies targeting destruction of cyclin D1 or its regulator E3 ligase selectively...
  83. ncbi Autoinhibition of the HECT-type ubiquitin ligase Smurf2 through its C2 domain
    Silke Wiesner
    Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada
    Cell 130:651-62. 2007
    ..Thus, interactions between C2 and HECT domains autoinhibit a subset of HECT-type E3s to protect them and their substrates from futile degradation in cells...
  84. ncbi ARF-BP1/Mule is a critical mediator of the ARF tumor suppressor
    Delin Chen
    Institute for Cancer Genetics, Department of Pathology, College of Physicians and Surgeons, Columbia University, 1150 St Nicholas Avenue, New York, New York 10032
    Cell 121:1071-83. 2005
    ..As such, ARF-BP1 may serve as a potential target for therapeutic intervention in tumors regardless of p53 status...
  85. ncbi Crystal structure of a UBP-family deubiquitinating enzyme in isolation and in complex with ubiquitin aldehyde
    Min Hu
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
    Cell 111:1041-54. 2002
    ..Binding by ubiquitin aldehyde induces a drastic conformational change in the active site that realigns the catalytic triad residues for catalysis...
  86. doi TRIM21 is essential to sustain IFN regulatory factor 3 activation during antiviral response
    Kai Yang
    Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    J Immunol 182:3782-92. 2009
    ....
  87. doi hCINAP is a novel regulator of ribosomal protein-HDM2-p53 pathway by controlling NEDDylation of ribosomal protein S14
    J Zhang
    1 State Key Lab of Protein and Plant Gene Research, Beijing, China 2 Department of Biochemistry and Molecular Biology, School of Life Sciences, Peking University, Beijing, China
    Oncogene 33:246-54. 2014
    ..These findings suggest that hCINAP is an important regulator of RP-HDM2-p53 pathway and a potential anticancer drug target. ..
  88. pmc Deubiquitination of NF-κB by Ubiquitin-Specific Protease-7 promotes transcription
    Amy Colleran
    Department of Biochemistry, University College Cork, Cork, Ireland
    Proc Natl Acad Sci U S A 110:618-23. 2013
    ..These findings reveal a unique mechanism controlling NF-κB activity and demonstrate that the deubiquitination of NF-κB by USP7 is critical for target gene transcription...
  89. doi Sumoylation of specificity protein 1 augments its degradation by changing the localization and increasing the specificity protein 1 proteolytic process
    Yi Ting Wang
    Institute of Basic Medical Sciences, National Cheng Kung University, Tainan 701, Taiwan
    J Mol Biol 380:869-85. 2008
    ..This interaction increased the efficiency of Sp1 proteolytic processing and ubiquitination and then resulted in Sp1 degradation. Therefore, sumoylation of Sp1 is attenuated during tumorigenesis in order to increase Sp1 stability...
  90. pmc The tumour suppressor CYLD is a negative regulator of RIG-I-mediated antiviral response
    Constantin S Friedman
    Immunology Institute, Mount Sinai School of Medicine, Box 1630, One Gustave L Levy Place, New York, New York 10029, USA
    EMBO Rep 9:930-6. 2008
    ..These findings show that CYLD is a negative regulator of RIG-I-mediated innate antiviral response...
  91. pmc Ubiquitin ligase Cbl-b is a negative regulator for insulin-like growth factor 1 signaling during muscle atrophy caused by unloading
    Reiko Nakao
    Department of Nutritional Physiology, Institute of Health Biosciences, University of Tokushima Graduate School, Kuramoto Cho, Tokushima, Japan
    Mol Cell Biol 29:4798-811. 2009
    ..The inhibition of Cbl-b-mediated ubiquitination may be a new therapeutic strategy for unloading-mediated muscle atrophy...
  92. pmc Phosphorylation and polyubiquitination of transforming growth factor beta-activated kinase 1 are necessary for activation of NF-kappaB by the Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor
    Virginie Bottero
    Department of Microbiology and Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA
    J Virol 85:1980-93. 2011
    ..Finally, inhibition of TAK1 by celastrol inhibited vGPCR-induced NF-κB activation, indicating this natural compound could be used as a potential therapeutic drug against KSHV malignancies involving vGPCR...
  93. doi Methylation by protein arginine methyltransferase 1 increases stability of Axin, a negative regulator of Wnt signaling
    B Cha
    Department of Life Science, The University of Seoul, Dongdaemun Gu, Seoul, Republic of Korea
    Oncogene 30:2379-89. 2011
    ..In summary, we show that the methylation of Axin occurred in vivo and controlled the stability of Axin. Therefore, methylation of Axin by PRMT1 may serve as a finely tuned regulation mechanism for Wnt/β-catenin signaling...
  94. doi Cellular inhibitors of apoptosis proteins cIAP1 and cIAP2 are required for efficient caspase-1 activation by the inflammasome
    Katherine Labbe
    Department of Microbiology and Immunology, McGill University, Montreal, Quebec H3G 0B1, Canada
    Immunity 35:897-907. 2011
    ..Our results describe a role for the cIAPs in innate immunity and further demonstrate the evolutionary conservation between cell death and inflammation mechanisms...
  95. pmc A novel role for XIAP in copper homeostasis through regulation of MURR1
    Ezra Burstein
    Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA
    EMBO J 23:244-54. 2004
    ..These findings represent the first described phenotypic alteration in Xiap-deficient mice and demonstrate that XIAP can function through MURR1 to regulate copper homeostasis...
  96. ncbi SUMO modification of Huntingtin and Huntington's disease pathology
    Joan S Steffan
    Department of Psychiatry and Human Behavior, Gillespie 2121, University of California, Irvine, CA 92697, USA
    Science 304:100-4. 2004
    ..Lysine mutations that prevent both SUMOylation and ubiquitination of Httex1p reduce HD pathology, indicating that the contribution of SUMOylation to HD pathology extends beyond preventing Htt ubiquitination and degradation...
  97. pmc The von Hippel-Lindau tumor suppressor protein and Egl-9-Type proline hydroxylases regulate the large subunit of RNA polymerase II in response to oxidative stress
    Olga Mikhaylova
    Department of Molecular Oncogenesis, Genome Research Institute, University of Cincinnati, Cincinnati, OH 45237 0505, USA
    Mol Cell Biol 28:2701-17. 2008
    ..These data indicate that through this novel pathway involving P1465 hydroxylation and Ser5 phosphorylation of Rbp1, pVHL may regulate tumor growth...
  98. pmc Phosphorylation by the c-Abl protein tyrosine kinase inhibits parkin's ubiquitination and protective function
    Han Seok Ko
    Neuroregeneration Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 107:16691-6. 2010
    ..Moreover, inhibition of c-Abl may be a neuroprotective approach in the treatment of PD...
  99. ncbi The deubiquitinating enzyme USP1 regulates the Fanconi anemia pathway
    Sebastian M B Nijman
    Division of Molecular Carcinogenesis and Center for Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Mol Cell 17:331-9. 2005
    ..We propose that USP1 deubiquitinates FANCD2 when cells exit S phase or recommence cycling after a DNA damage insult and may play a critical role in the FA pathway by recycling FANCD2...
  100. ncbi Ataxin-3 binds VCP/p97 and regulates retrotranslocation of ERAD substrates
    Xiaoyan Zhong
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6084, USA
    Hum Mol Genet 15:2409-20. 2006
    ..These data suggest that a normal function of AT3 is to regulate flow through the ERAD pathway by modulating VCP-dependent extraction of proteins from the ER...
  101. pmc The E3 ubiquitin ligase Itch controls the protein stability of p63
    Mario Rossi
    Medical Research Council, Toxicology Unit, Leicester University, Leicester LE1 9HN, United Kingdom
    Proc Natl Acad Sci U S A 103:12753-8. 2006
    ..These data suggest that Itch has a fundamental role in the mechanism that controls endogenous p63 protein levels and therefore contributes to regulation of p63 in physiological conditions...

Research Grants76

  1. ATP-Ubiquitin Dependent Proteolysis
    Arthur L Haas; Fiscal Year: 2011
    ..proteins and will examine the role of the carboxyl terminal 2-grasp domain as a specificity filter for cognate E2/Ubc recognition, the role of 2-grasp domain versus Ubc12 amino-terminal peptide binding in transition state ..
  2. Yousef Abu-Amer; Fiscal Year: 2016
    ..that a variety of upstream signals augment ubiquitination-based signaling network dominated by TAK1/TABs/RIP/NEMO/UBC complex. Thus, we propose to investigate the following specific aims: 1...
  3. Ali Syed Arbab; Fiscal Year: 2014
    ..athymic mouse will be replaced by bone marrow cells collected from bone marrow of transgenic mouse (C57BL/6-Tg(UBC-GFP)30Scha/J) that express GFP protein under the control of human ubiquitin C promoter...
  4. Cynthia A Lemere; Fiscal Year: 2014
    ..We will generate C3fl/fl;UBC-Cre-ERT2+/- mice by crossing the C3fl/fl mice from Aim 1 to ubiquitin-promoter driven Cre-Estrogen receptor 2 mice, ..
  5. Analysis of ubiquitination enzymes in C. elegans
    Lynn Boyd; Fiscal Year: 2009
    ..Previous studies into the ubiquitin pathway in C. elegans identified more than 20 ubiquitin conjugating enzymes (Ubc) and greater than a hundred ubiquitin ligases (E3)...
  6. Transgenic rat overexpressing miR-15/16 cluster:functional implications in develo
    Junming Yue; Fiscal Year: 2010
    ..diseases, the investigator proposes to generate two transgenic rat models: one is a ubiquitous transgenic rat (UBC-miR-15/16) that expresses miR-15/16 in all tissues using a human ubiquitin C promoter (UBC) in a lentiviral vector;..
  7. UBIQUITIN DEFICIENCY IN AGING AND NEURODEGENERATION
    Ron Kopito; Fiscal Year: 2006
    ..Mice harboring deletions of the two polyubiquitin genes, UbB and UbC will be bred and intercrossed to produce lines containing progressively severe ubiquitin deficiencies...
  8. Adenosine, Toll-Like Receptors and Angiogenesis
    Samuel Joseph Leibovich; Fiscal Year: 2011
    ..A2ARs deleted in both endothelial and hematopoietic cells, reconstitution with bone marrow from wild type mice (UbC-GFP mice) will be performed. 4. The role of the macrophage HIF11-I.1 isoform in wound healing: HIF11-I...
  9. Cerebellar Microcircuits: Organization &Development
    Marco Martina; Fiscal Year: 2012
    ..The UBC has typically only one dendrite that terminates with a brush of dendrioles;these establish a giant excitatory ..
  10. Carolina Borges-Merjane; Fiscal Year: 2014
    ..Aim 1 will determine the physiological postsynaptic response of GrCs to UBC mediated input These experiments will directly test for the first time the effect of UBCs input to GrCs using ..
  11. Distinguishing adipose stromal vs. stem cells by serial transplantation
    Bruce A Bunnell; Fiscal Year: 2013
    ..Aim 1 will employ the C57BL/6-Tg (UBC-GFP) 30cha/J mouse model as a source of easily trackable GFP+ adipose derived SVF cells or ASCs...
  12. Translational Science in Integrative Oncology: From Bedside, to Bench, to Best P
    Suzanna M Zick; Fiscal Year: 2013
    ..The 2 and 1/2-day meeting is co-hosted by the University of British Columbia (UBC) Faculty of Medicine's Division of Continuing Professional Development and the UBC School of Nursing...
  13. Kathleen E Malone; Fiscal Year: 2014
    ..Epidemiology (WECARE) II Study is a population-based study of 800 CBC cases and 800 unilateral breast cancer (UBC) controls currently being recruited and interviewed, along with having their breast cancer diagnosis and treatment ..
  14. Peter S Nelson; Fiscal Year: 2016
    ..institutions;3) the University of British Columbia and the Prostate Centre of Vancouver General Hospital (UBC);and 4) Oregon Health and Science University (OHSU)...
  15. Hua Yang; Fiscal Year: 2014
    ..Part of the descending information passes through a cell type, the unipolar brush cell (UBC), whose physiological role in the circuit is poorly understood...
  16. NOVEL FAS BINDING PROTEIN AND ITS ROLE IN DISEASE
    Raif Geha; Fiscal Year: 1999
    ..FAP shows strong homology to the recently cloned ubiquitin conjugating (UBC) enzyme UBC9 which controls yeast cell cycle progression from G2 to mitosis and regulates the degradation of S and ..
  17. REGULATION OF GROWTH ARREST IN HYPEROXIC NEONATAL LUNG
    Sharon McGrath Morrow; Fiscal Year: 2001
    ..Using subtractive hybridization a novel ubiquitin conjugating enzyme 2 (Ubc-2) was isolated and found to be markedly downregulated during hyperoxia...
  18. Cb1-b in T Cell Activation and Tolerance
    Yun Cai Liu; Fiscal Year: 2006
    ..that the RING finger of Cbl, a Cbl-b homologue, can recruit and activate ubiquitin (Ub) conjugation enzyme (Ubc), and that Cbl then facilitates Ub conjugation to the protein tyrosine kinases it associates with, may suggest that ..
  19. Mechanisms of myometrial healing and regeneration
    Catalin Buhimschi; Fiscal Year: 2006
    ..to: (1) investigate molecular and structural aspects of uterine wound healing in MRL/MpJ+/+; C57BL/6 ; C57BL/6-Tg(UBC-GFP)30Scha and B6...
  20. STRUCTURE/FUNCTION OF UBIQUITIN CONJUGATING ENZYMES
    Vincent Chau; Fiscal Year: 1999
    ..of protein ubiquitination is conferred by a family of related proteins known as ubiquitin conjugating-enzymes (Ubc)...
  21. Reconstitution of T cell immunity after UCB transplantation: The role of Treg
    Vassiliki Boussiotis; Fiscal Year: 2009
    ..Early studies with single UCB transplants have demonstrated reduced GvHD in unrelated UBC transplant recipients compared to unrelated BMT recipients...
  22. FUNCTION OF AN INTERFERON INDUCED UBIQUITIN HOMOLOG
    Arthur Haas; Fiscal Year: 2003
    ..bear remarkable yet cryptic sequence similarity to the conserved catalytic domain of ubiquitin conjugating enzymes (Ubc). The present proposal comprises three specific aims...
  23. MECHANISM OF HPV E6 MEDIATED UBIQUITINATION OF P53
    Peter Howley; Fiscal Year: 1999
    ..characterize the E6 associated protein; (ii) to determine additional proteins associated with E6-AP and with the E6/E6-AP complex; and (iii) to clone and characterize the mammalian UBC's involved in the E6 mediated degradation of p53.
  24. DEGRADATION OF E12/E47 IN SMOOTH MUSCLE CELLS
    Gordon Huggins; Fiscal Year: 2002
    ..They are expressed in VSMC. The applicant cloned a novel ubiquitin conjugating enzyme, UBC-E2A, directed against the E12 and E47...
  25. CBL IN T CELL ACTIVATION
    Yun Cai Liu; Fiscal Year: 2006
    ..through the interaction of Cbl protein binding domains and through the RING finger-dependent recruitment of Ubc E2s; Second, Cbl negatively regulates intracellular signal transduction in thymocytes and peripheral T cells via ..
  26. Colon Cancer Inhibition by a Class of PPARgamma Agonists
    Stephen Safe; Fiscal Year: 2009
    ..The proposed studies will provide mechanistic insights on PPARy-dependent inhibition of colon cancer and identify compounds for future clinical studies. ..
  27. Renal Cell Injury in Diabetes
    Karen Block; Fiscal Year: 2008
    ..Elucidating these events may allow future modulation of the enzymatic complex(es) to prevent oxidative stress implicated in cellular injury in diabetes. [unreadable] [unreadable]..
  28. Post Translation Regulation in Mycobacteria
    Luiz Bermudez; Fiscal Year: 2008
    ..In case we confirm our hypothesis, future work will address the role of Ion in M. tuberculosis [unreadable] [unreadable] [unreadable]..
  29. REGULATION OF GENE EXPRESSION BY OXYGEN
    MARIA CZYZYK KRZESKA; Fiscal Year: 2005
    ..An understanding of the physiological role of pVhl in regulation of gene expression during hypoxia will provide much needed information on how O2-sensitive cells respond and adapt to hypoxia. ..
  30. Inhibition of Pancreatic Cancer by New PPARgamma Agonis*
    Stephen Safe; Fiscal Year: 2008
    ..PPAR? -active C-substituted DIMs that inhibit pancreatic cancer cell growth in vitro and in vivo, and these will serve as lead compounds for development of new drugs for clinical treatment of this devastating disease ..
  31. Role of KLF6 in the DNA damage response and apoptosis
    Michaela Banck; Fiscal Year: 2008
    ..unreadable] The proposal is aimed at preparing the applicant in the responsible conduct of research with a disease focus on basic investigations in gastrointestinal malignancies [unreadable] [unreadable]..
  32. Role of HHcy in diabetic vascular disease
    Hong Wang; Fiscal Year: 2010
    ..If we can identify the key events in Hcy-induced atherosclerosis in diabetes, genetic or biochemical approaches to block these steps could lead to new therapeutic approaches ..
  33. "Studies to examine Centrin's role in DNA repair"
    Kiran Madura; Fiscal Year: 2010
    ..However, the function of Rad4 is not well understood, and its characterization is the focus of this application. ..
  34. Therapeutic Intervention for Tauopathies
    Chad Dickey; Fiscal Year: 2007
    ..Those compounds with the greatest promise based on in vitro analyses will then be used in animal models for tauopathy that are exclusive to the Mayo Clinic. [unreadable] [unreadable]..
  35. MYCOBACTERIAL ENVIRONMENT WITHIN MACROPHAGES
    Luiz Bermudez; Fiscal Year: 2003
    ..We believe that the proposed studies will generate important information about the phagosome environment and the mycobacterial response to it. ..
  36. Uterine Vascular Adaptation to Pregnancy
    Lubo Zhang; Fiscal Year: 2005
    ..Such an understanding has obvious clinical implications because the maladaptation of uterine circulation to pregnancy is associated with fetal developmental abnormalities and maternal cardiovascular disorders. ..
  37. MEKK2/3-MEK5 Interaction/Activation/ERK5 Pathway(RMI)
    BRUCE CUEVAS; Fiscal Year: 2005
    ....
  38. Cocaine and Apoptosis in the Developing Heart
    Lubo Zhang; Fiscal Year: 2004
    ..Such an understanding has obvious clinical implications because the increasing information has pointed to an important role of apoptosis in cardiovascular diseases. ..
  39. INITIAL STEPS IN RAAV TRANSDUCTION
    Matthew Weitzman; Fiscal Year: 2003
    ..Studying the functions of E4orf6 and its cellular targets will suggest simple ways to increase the efficiency of rAAV vectors. ..
  40. AAV and the DNA Damage Machinery
    Matthew D Weitzman; Fiscal Year: 2010
    ..Therefore, in addition to providing insights into the fundamental process of recognition of damaged DNA, these studies will also have implications for genetic approaches to combat disease. ..
  41. Mechanisms of Arterial Wall-Mediated Atherogenesis
    Neil Freedman; Fiscal Year: 2008
    ..In so doing, this project should build a foundation for identifying multiple arterial wall gene products that may serve as therapeutic targets for atherosclerosis. ..
  42. REGULATION OF SECRETION FROM HUMAN BASOPHILS
    Donald MacGlashan; Fiscal Year: 2009
    ..A population of subjects will be examined for this relationship. ..
  43. STRUCTURE/FUNCTION OF HIV1 CAPSID/CYCLOPHILIN COMPLEX
    Wesley Sundquist; Fiscal Year: 2001
    ..Finally, genetic analysis of mutants of CA in an HIV provirus will be used to test models that arise from the CA and CA-cyclophilin structures. ..
  44. Desensitization of Vascular Receptor Tyrosine Kinases
    Neil Freedman; Fiscal Year: 2009
    ..Therapeutic implications for cardiovascular diseases may derive from determining how GRKs regulate RPTK signaling, and which RPTKs are subject to GRK-mediated regulation. ..
  45. ALKYL PCDFS--INHIBITION OF MAMMARY CANCER
    Stephen Safe; Fiscal Year: 2001
    ..Thus the proposed studies will define a new mechanism-based class of antiestrogens that can be used alone or in combination with tamoxifen for treatment of breast and endometrial cancer. ..
  46. ACTIVE CONTROL OF WORKPLACE NOISE EXPOSURE
    Murray Hodgson; Fiscal Year: 2002
    ..The results of the research will be generalized to produce guidelines allowing the feasibility of reducing noise exposure using ANC, and the expected associated noise reductions and costs, to be evaluated in other workplaces. ..
  47. Biochemical Characterization of Parkin
    Kiran Madura; Fiscal Year: 2003
    ..iv). Our long-term objective is to characterize the ubiquitination of a-Syn and other physiological substrates by Parkin. ..
  48. Structure/Function Studies of Quinone Reductase 2
    Zhongtao Zhang; Fiscal Year: 2009
    ....
  49. LIPOCORTINS (ANNEXINS) AND METAL-INDUCED MUTAGENESIS
    Fusao Hirata; Fiscal Year: 2003
    ..Our proposed research will provide further insights to understanding of the molecular mechanisms of carcinogenesis, genetic instability and pathological diseases associated with the formation of mutations by heavy metals. ..
  50. Novel Function of PI 3-Kinase in Calcium Regulation
    Ching Shih Chen; Fiscal Year: 2004
    ..These studies will help understand how the PI(3,4,5)P3-binding protein mediates Ca2+ entry across the plasma membrane. ..
  51. Divalent Metal Transporter: Role in Manganese Toxicity
    JEROME ROTH; Fiscal Year: 2004
    ....
  52. Muscle-Specific Nutritional Adaptations to Catabolic States
    S Russ Price; Fiscal Year: 2010
    ..New information regarding the mechanisms of muscle atrophy may identify therapeutic targets to reduce morbidity and mortality of chronically ill patients and improve their quality of life. ..
  53. BACTERIAL MODULATION OF EPITHELIAL SIGNALING PATHWAYS
    Andrew Neish; Fiscal Year: 2003
    ..Finally, a novel electroporation based method to introduce purified proteins into intact model epithelia will be used to dissect the cellular responses to internalization of a variety of bacterial effector proteins. ..
  54. TOXICOLOGY OF ENVIRONMENT CONTAMINANTS
    Stephen Safe; Fiscal Year: 2007
    ..The proposed training program will continue to provide trainees with a challenging academic and research environment that will prepare them for future careers in academic, industry and government. ..
  55. Signaling Mechanisms Regulation Muscle Protein Turnover
    S Price; Fiscal Year: 2005
    ..Lastly, we will study adrenalectomized rats to determine if glucocorticoids can be linked to inhibition of SGK activity or activation of the MEK/ERK MAPK pathway in skeletal muscle. ..
  56. Apoptosis Regulation by Lipid Signals in Prostate Cancer
    Ching Shih Chen; Fiscal Year: 2005
    ..Identification of new anti-cancer agents whose mode of action is distinct from existing chemotherapeutic regimens will foster new therapeutic strategies. ..
  57. Novel Celecoxib Derivatives as Chemopreventive Agents
    Ching Shih Chen; Fiscal Year: 2005
    ..In parallel, we will examine the safety of chronic oral treatment with these compounds in non-carcinogen-treated tumor-free animals. ..
  58. Smad4 Stability by beta-TrCP1 in Pancreatic Cancer
    Mei Wan; Fiscal Year: 2005
    ..abstract_text> ..
  59. 2,3,7,8,--TCDD Effects on the Estrogenic Responses
    Stephen Safe; Fiscal Year: 2006
    ..The proposed Aims will address important mechanistic considerations on IDRE-independent inhibitory AhR-ERa crosstalk and pathways critical for inhibition of mammary tumor growth by SAhRMs. ..
  60. Epithelial Responses to Enteric Organisms
    Andrew Neish; Fiscal Year: 2005
    ..More significantly, these data will be invaluable in the recognition of these signatures in human diseases potentially associated with infection by known and unknown organisms. ..
  61. Coactivation of Estrogen Receptor alpha/Sp1
    Stephen Safe; Fiscal Year: 2006
    ..abstract_text> ..
  62. Gene Therapy, Neural Grafts & Parkinson's Disease
    DAVID YUREK; Fiscal Year: 2005
    ..These studies will also determine if combinations of viral vectors expressing different neurotrophic factors can be used to improve the therapeutic effects of dopamine grafts. ..
  63. DNA Replication and Genome Integrity
    Matthew Weitzman; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  64. RIP2 kinase's function in Innate Immunity
    Derek Abbott; Fiscal Year: 2007
    ..This grant application aims to define the preferred peptide phosphorylation sites of RIP2, to map the phosphorylation site of TRAF6 and to identify the physiologic significance of RIP2's phosphorylation of TRAF6. ..
  65. The role of hMLH1-hMRE11 in DNA mismatch repair
    Chengtao Her; Fiscal Year: 2007
    ..abstract_text> ..
  66. Aging, Atherosclerosis, and the Arterial Wall
    Neil Freedman; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  67. Regulation of Cell Function by Intermittent Hypoxia
    MARIA CZYZYK KRZESKA; Fiscal Year: 2007
    ..3) We will determine the role of proline hydroxylation in Rpb1 ubiquitination by VHL and measure the effects of IH and oxidative stress on proline hydroxylation in brain extracts from exposed animals, and in PC12 cells. ..
  68. CHIP: A Link between Parkin and Cell Death
    Leonard Petrucelli; Fiscal Year: 2007
    ..It is our focus to resolve the mechanisms by which CHIP regulates parkin cell biology in vivo, and how this may be applicable to the clinical/neuropathological spectrum of presentation in ARJP. ..
  69. Chaperone-mediated signaling in Alzheimer's disease
    Chad Dickey; Fiscal Year: 2007
    ..Specifically, we intend to focus on the removal of the proteins once they have already started to accumulate in an effort to reverse the progression of the disease rather than prevent it. [unreadable] [unreadable] [unreadable]..
  70. Targeting active adaptors to control endothelial damage
    Sheng Wei; Fiscal Year: 2008
    ..g. design of DAP10 and DAP12 antagonists, for therapeutic intervention to specifically control lymphocyte-mediated tissue damage. [unreadable] [unreadable]..
  71. Stem Cell Adaptability in Parkinson' Disease
    DAVID YUREK; Fiscal Year: 2009
    ..The variable of host age on ESC-derived dopamine neuron adaptability will be studied. ..
  72. Mechanisms of Growth Factor-Estrogen Receptor Crosstalk
    Stephen Safe; Fiscal Year: 2006
    ..abstract_text> ..
  73. Interactions of AAV with Cellular Factors
    Matthew Weitzman; Fiscal Year: 2006
    ..Understanding the role of cellular components in regulating AAV replication and integration will enhance our ability both to produce and utilize this promising vector system. ..
  74. Homocysteine-induced Endothelial Cell Growth Inhibition
    Hong Wang; Fiscal Year: 2008
    ..If we can identify the key events in Hcy-induced arteriosclerosis, genetic or biochemical approaches to block these steps could lead to therapeutic advantage. ..
  75. VPR-INDUCED ENDOTHELIAL CYTOSKELETAL/FUNCTIONAL CHANGES
    Ling Jun Zhao; Fiscal Year: 2002
    ..We anticipate that this project will generate novel knowledge about the mechanism of Vpr induced cytoskeletal/functional changes in endothelial cells that can benefit the designing of therapeutic strategies. ..