ubiquitin conjugating enzymes

Summary

Summary: A class of enzymes that form a thioester bond to UBIQUITIN with the assistance of UBIQUITIN-ACTIVATING ENZYMES. They transfer ubiquitin to the LYSINE of a substrate protein with the assistance of UBIQUITIN-PROTEIN LIGASES.

Top Publications

  1. ncbi Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain
    L Deng
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas 75390, USA
    Cell 103:351-61. 2000
  2. ncbi Structure of a c-Cbl-UbcH7 complex: RING domain function in ubiquitin-protein ligases
    N Zheng
    Cellular Biochemistry and Biophysics Program, Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Cell 102:533-9. 2000
  3. 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
  4. ncbi Mechanisms underlying ubiquitination
    C M Pickart
    School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, Maryland 21205, USA
    Annu Rev Biochem 70:503-33. 2001
  5. pmc The error-free component of the RAD6/RAD18 DNA damage tolerance pathway of budding yeast employs sister-strand recombination
    Hengshan Zhang
    Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
    Proc Natl Acad Sci U S A 102:15954-9. 2005
  6. ncbi Chaperoned ubiquitylation--crystal structures of the CHIP U box E3 ubiquitin ligase and a CHIP-Ubc13-Uev1a complex
    Minghao Zhang
    Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, United Kingdom
    Mol Cell 20:525-38. 2005
  7. pmc SUMO-1 modification activates the transcriptional response of p53
    M S Rodriguez
    School of Biomedical Science, BMS Building, University of St Andrews, St Andrews, Fife KY16 9ST
    EMBO J 18:6455-61. 1999
  8. ncbi A regulatory link between ER-associated protein degradation and the unfolded-protein response
    R Friedlander
    Max Delbruck Centrum fur Molekulare Medizin, Berlin, Germany
    Nat Cell Biol 2:379-84. 2000
  9. pmc Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex
    Lingyan Jin
    Department of Molecular and Cell Biology, 16 Barker Hall, University of California at Berkeley, Berkeley, CA 94720 3202, USA
    Cell 133:653-65. 2008
  10. pmc SUMO-targeted ubiquitin ligases in genome stability
    John Prudden
    Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    EMBO J 26:4089-101. 2007

Detail Information

Publications251 found, 100 shown here

  1. ncbi Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain
    L Deng
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas 75390, USA
    Cell 103:351-61. 2000
    ..These results unveil a new regulatory function for ubiquitin, in which IKK is activated through the assembly of K63-linked polyubiquitin chains...
  2. ncbi Structure of a c-Cbl-UbcH7 complex: RING domain function in ubiquitin-protein ligases
    N Zheng
    Cellular Biochemistry and Biophysics Program, Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Cell 102:533-9. 2000
    ....
  3. 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...
  4. ncbi Mechanisms underlying ubiquitination
    C M Pickart
    School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, Maryland 21205, USA
    Annu Rev Biochem 70:503-33. 2001
    ..The new findings shed light on many aspects of E3 structure, function, and mechanism, but also emphasize that key features of E3 catalysis remain to be elucidated...
  5. pmc The error-free component of the RAD6/RAD18 DNA damage tolerance pathway of budding yeast employs sister-strand recombination
    Hengshan Zhang
    Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
    Proc Natl Acad Sci U S A 102:15954-9. 2005
    ....
  6. ncbi Chaperoned ubiquitylation--crystal structures of the CHIP U box E3 ubiquitin ligase and a CHIP-Ubc13-Uev1a complex
    Minghao Zhang
    Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, United Kingdom
    Mol Cell 20:525-38. 2005
    ....
  7. pmc SUMO-1 modification activates the transcriptional response of p53
    M S Rodriguez
    School of Biomedical Science, BMS Building, University of St Andrews, St Andrews, Fife KY16 9ST
    EMBO J 18:6455-61. 1999
    ..The SUMO-1 modification pathway therefore acts as a potential regulator of the p53 response and may represent a novel target for the development of therapeutically useful modulators of the p53 response...
  8. ncbi A regulatory link between ER-associated protein degradation and the unfolded-protein response
    R Friedlander
    Max Delbruck Centrum fur Molekulare Medizin, Berlin, Germany
    Nat Cell Biol 2:379-84. 2000
    ..However, when stress is applied, the UPR is required to increase ERAD activity. We thus demonstrate, for the first time, a regulatory loop between ERAD and the UPR, which is essential for normal growth of yeast cells...
  9. pmc Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex
    Lingyan Jin
    Department of Molecular and Cell Biology, 16 Barker Hall, University of California at Berkeley, Berkeley, CA 94720 3202, USA
    Cell 133:653-65. 2008
    ..We propose that recognition of similar motifs in substrates and ubiquitin enables the APC/C to assemble ubiquitin chains with the specificity and efficiency required for tight cell-cycle control...
  10. pmc SUMO-targeted ubiquitin ligases in genome stability
    John Prudden
    Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    EMBO J 26:4089-101. 2007
    ..The DNA repair factor Rad60 and its human homolog NIP45, which contain SLDs, are candidate STUbL targets. Consistently, Rad60 and Slx8-Rfp mutants have similar DNA repair defects...
  11. ncbi A field guide to ubiquitylation
    S Fang
    Medical Biotechnology Center, University of Maryland Biotechnology Institute, 725 W Lombard Street, 21201, Baltimore, Maryland 21202, USA
    Cell Mol Life Sci 61:1546-61. 2004
    ..by interactions of substrates with specific ubiquitin protein ligases (E3s) in association with ubiquitin conjugating enzymes (E2s)...
  12. ncbi Molecular insights into polyubiquitin chain assembly: crystal structure of the Mms2/Ubc13 heterodimer
    A P VanDemark
    Department of Biophysics and Biophysical Chemistry, School of Medicine, Johns Hopkins University, Baltimore, MD, USA
    Cell 105:711-20. 2001
    ..Selective mutations in the channels suggest a molecular model for specificity in the assembly of Lys63-linked polyubiquitin signals...
  13. ncbi Hrd1p/Der3p is a membrane-anchored ubiquitin ligase required for ER-associated degradation
    N W Bays
    Section of Cell and Developmental Biology, Division of Biology, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093 0347, USA
    Nat Cell Biol 3:24-9. 2001
    ..In this capacity, Hrd1p has an apparent preference for misfolded proteins. We also show that Hrd1p functions as an E3 in vivo, using only Ubc7p or Ubc1p to specifically program the ubiquitination of ERAD substrates...
  14. ncbi Ubc9p is the conjugating enzyme for the ubiquitin-like protein Smt3p
    E S Johnson
    Laboratory of Cell Biology, Howard Hughes Medical Institute, Rockefeller University, New York, New York 10021, USA
    J Biol Chem 272:26799-802. 1997
    ..cerevisiae. These results suggest that, like ubiquitination, Smt3p conjugation may be a critical modification in cell cycle regulation...
  15. ncbi ER degradation of a misfolded luminal protein by the cytosolic ubiquitin-proteasome pathway
    M M Hiller
    Institut für Biochemie der Universität Stuttgart, Pfaffenwaldring 55, D 70569 Stuttgart, Germany
    Science 273:1725-8. 1996
    ..It is likely that CPY* entered the ER, was glycosylated, and was then transported back out of the ER lumen to the cytoplasmic side of the organelle, where it was conjugated with ubiquitin and degraded...
  16. ncbi SUMO-modified PCNA recruits Srs2 to prevent recombination during S phase
    Boris Pfander
    Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany
    Nature 436:428-33. 2005
    ..Our finding suggests a model in which SUMO-modified PCNA recruits Srs2 in S phase in order to prevent unwanted recombination events of replicating chromosomes...
  17. ncbi Ubch9 conjugates SUMO but not ubiquitin
    J M Desterro
    School of Biomedical Science, University of St Andrews, Fife, UK
    FEBS Lett 417:297-300. 1997
    b>Ubiquitin conjugating enzymes participate in the thioester cascade that leads to protein ubiquitination...
  18. ncbi Mms2-Ubc13 covalently bound to ubiquitin reveals the structural basis of linkage-specific polyubiquitin chain formation
    Michael J Eddins
    Department of Biophysics and Biophysical Chemistry and the Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Nat Struct Mol Biol 13:915-20. 2006
    ..The structure reveals the key role of Mms2 in allowing selective insertion of Lys63 into the Ubc13 active site and suggests a molecular model for polyubiquitin chain elongation...
  19. ncbi TAK1 is a ubiquitin-dependent kinase of MKK and IKK
    C Wang
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9148, USA
    Nature 412:346-51. 2001
    ..We also provide evidence that TRAF6 is conjugated by the K63 polyubiquitin chains. These results indicate that ubiquitination has an important regulatory role in stress response pathways, including those of IKK and JNK...
  20. pmc Rad18 guides poleta to replication stalling sites through physical interaction and PCNA monoubiquitination
    Kenji Watanabe
    Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan
    EMBO J 23:3886-96. 2004
    ..These results suggest that Rad18 is crucial for recruitment of poleta to the damaged site through protein-protein interaction and PCNA monoubiquitination...
  21. ncbi The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage
    Grant S Stewart
    Cancer Research UK, Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham, UK
    Cell 136:420-34. 2009
    ..These RNF168-dependent chromatin modifications orchestrate the accumulation of 53BP1 and BRCA1 to DNA lesions, and their loss is the likely cause of the cellular and developmental phenotypes associated with RIDDLE syndrome...
  22. pmc Orchestration of the DNA-damage response by the RNF8 ubiquitin ligase
    Nadine K Kolas
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto M5G1X5, Ontario, Canada
    Science 318:1637-40. 2007
    ..These results demonstrate how the DNA-damage response is orchestrated by ATM-dependent phosphorylation of MDC1 and RNF8-mediated ubiquitination...
  23. pmc DNA damage-dependent acetylation and ubiquitination of H2AX enhances chromatin dynamics
    Tsuyoshi Ikura
    Department of Biochemistry, Tohoku University Graduate School of Medicine, Seiryoumachi 2 1, Aobaku Sendai 980 8575, Japan
    Mol Cell Biol 27:7028-40. 2007
    ..We conclude that the sequential acetylation and ubiquitination of H2AX by TIP60-UBC13 promote enhanced histone dynamics, which in turn stimulate a DNA damage response...
  24. pmc Quantitative proteomics reveals the function of unconventional ubiquitin chains in proteasomal degradation
    Ping Xu
    Department of Human Genetics, Center for Neurodegenerative Diseases, Emory University, Atlanta, GA 30322, USA
    Cell 137:133-45. 2009
    ..Ubc6 primarily synthesizes K11-linked chains, and K11 linkages function in the ERAD pathway. Thus, unconventional polyubiquitin chains are critical for ubiquitin-proteasome system function...
  25. pmc TEB4 is a C4HC3 RING finger-containing ubiquitin ligase of the endoplasmic reticulum
    Gerco Hassink
    Department of Medical Microbiology, Leiden University Medical Center, P O Box 9600, 2300 RC Leiden, The Netherlands
    Biochem J 388:647-55. 2005
    ..These properties are reminiscent of E3 enzymes, which are involved in ER-associated protein degradation. TEB4 is an ER degradation substrate itself, promoting its own degradation in a RING finger- and proteasome-dependent manner...
  26. ncbi The SUMO conjugating enzyme Ubc9 is a regulator of GLUT4 turnover and targeting to the insulin-responsive storage compartment in 3T3-L1 adipocytes
    Li bin Liu
    Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Showa machi, Maebashi, Japan
    Diabetes 56:1977-85. 2007
    ..Thus, Ubc9 is a pivotal regulator of the insulin sensitivity of glucose transport in adipocytes...
  27. ncbi UBC13, a DNA-damage-inducible gene, is a member of the error-free postreplication repair pathway in Saccharomyces cerevisiae
    J Brusky
    Department of Microbiology and Immunology, University of Saskatchewan, Saskatoon, Canada
    Curr Genet 37:168-74. 2000
    ..The involvement of UBC13 in cellular tolerance to DNA-damage is further implicated by our finding that the UBC13 transcript level is increased up to 6-fold in response to DNA-damage...
  28. pmc The unique N terminus of the UbcH10 E2 enzyme controls the threshold for APC activation and enhances checkpoint regulation of the APC
    Matthew K Summers
    Department of Cellular Regulation, Genentech Inc, South San Francisco, CA 94080, USA
    Mol Cell 31:544-56. 2008
    ..Thus, UbcH10 combines a specific E2-E3 interface and regulation via its N-terminal extension to limit APC activity for substrate selection and checkpoint control...
  29. pmc Ubc13/Rnf8 ubiquitin ligases control foci formation of the Rap80/Abraxas/Brca1/Brcc36 complex in response to DNA damage
    Bin Wang
    Department of Genetics, Howard Hughes Medical Institute, Center for Genetics and Genomics, Brigham and Women s Hospital, Harvard University Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 104:20759-63. 2007
    ..This sequential E3 ubiquitin ligase recruitment constitutes a ubiquitin ligase cascade required for DNA repair and checkpoint signaling...
  30. 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...
  31. pmc Identification of a physiological E2 module for the human anaphase-promoting complex
    Adam Williamson
    Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
    Proc Natl Acad Sci U S A 106:18213-8. 2009
    ..We conclude that UbcH10 and Ube2S constitute a physiological E2-module for APC/C, the activity of which is required for spindle assembly and cell division...
  32. ncbi Structure of a Shigella effector reveals a new class of ubiquitin ligases
    Yongqun Zhu
    National Institute of Biological Sciences, 7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, China
    Nat Struct Mol Biol 15:1302-8. 2008
    ..Our analysis establishes a structurally and mechanistically distinct class of ubiquitin ligases found exclusively in pathogenic or symbiotic bacteria...
  33. ncbi A bacterial inhibitor of host programmed cell death defenses is an E3 ubiquitin ligase
    Radmila Janjusevic
    Laboratory of Structural Microbiology, Rockefeller University, New York, NY 10021, USA
    Science 311:222-6. 2006
    ..These results show that Pseudomonas syringae uses a mimic of host E3 ubiquitin ligases to inactivate plant defenses...
  34. pmc Members of the PIAS family act as SUMO ligases for c-Jun and p53 and repress p53 activity
    Darja Schmidt
    Max Planck Institute of Biochemistry, Department of Molecular Cell Biology, Am Klopferspitz 18a, D 82152 Martinsried, Germany
    Proc Natl Acad Sci U S A 99:2872-7. 2002
    ..Strikingly, PIAS proteins strongly repress the transcriptional activity of p53, suggesting that the PIAS-SUMO pathway plays a crucial role in the regulation of p53 and presumably other transcription factors...
  35. pmc Human SHPRH suppresses genomic instability through proliferating cell nuclear antigen polyubiquitination
    Akira Motegi
    Genome Instability Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 175:703-8. 2006
    ..Therefore, the yRad5/SHPRH-dependent pathway is a conserved and fundamental DNA repair mechanism that protects the genome from genotoxic stress...
  36. pmc A novel protein modification pathway related to the ubiquitin system
    D Liakopoulos
    ZMBH, Zentrum fur Molekulare Biologie der Universitat Heidelberg, Im Neuenheimer Feld 282, D 69120 Heidelberg, Germany
    EMBO J 17:2208-14. 1998
    ..This suggests that the RUB1 conjugation pathway is functionally affiliated to the ubiquitin-proteasome system and may play a regulatory role...
  37. ncbi Role of a ubiquitin-conjugating enzyme in degradation of S- and M-phase cyclins
    W Seufert
    Friedrich Miescher Laboratorium der Max Planck Gesellschaft, Tubingen, Germany
    Nature 373:78-81. 1995
    ..Thus distinct degradation signals or regulated interaction with the ubiquitin-protein ligase system may determine the cell-cycle specificity of cyclin proteolysis...
  38. pmc APC2 Cullin protein and APC11 RING protein comprise the minimal ubiquitin ligase module of the anaphase-promoting complex
    Z Tang
    Departments of Pharmacology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390 9041, USA
    Mol Biol Cell 12:3839-51. 2001
    ..Surprisingly, with Ubc4 as the E2 enzyme, Zn(2+) ions alone are sufficient to catalyze the ubiquitination of cyclin B1. Therefore, the Zn(2+) ions of the RING finger family of ubiquitin ligases may be directly involved in catalysis...
  39. ncbi Histone ubiquitination and chromatin remodeling in mouse spermatogenesis
    W M Baarends
    Department of Endocrinology and Reproduction, Erasmus University, Rotterdam, Rotterdam, 3000 DR, The Netherlands
    Dev Biol 207:322-33. 1999
    ..The postmeiotic uH2A immunoexpression in elongating spermatids indicates that nucleosome destabilization induced by histone ubiquitination may play a facilitating role during histone-to-protamine replacement...
  40. pmc A ubiquitin mutant with specific defects in DNA repair and multiubiquitination
    J Spence
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115
    Mol Cell Biol 15:1265-73. 1995
    ..The results of this study suggest that Lys-63 is used as a linkage site in the formation of novel multiubiquitin chain structures that play an important role in DNA repair...
  41. pmc DNA damage checkpoints are involved in postreplication repair
    Leslie Barbour
    Department of Microbiology and Immunology, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E5, Canada
    Genetics 174:1789-800. 2006
    ..These results suggest that a damage checkpoint is essential for tolerance mediated by both the error-free and error-prone branches of PRR...
  42. ncbi Transient global cerebral ischemia induces a massive increase in protein sumoylation
    Wei Yang
    Department of Anesthesiology, Multidisciplinary Neuroprotection Laboratories, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Cereb Blood Flow Metab 28:269-79. 2008
    ....
  43. pmc Ubiquitination and translocation of TRAF2 is required for activation of JNK but not of p38 or NF-kappaB
    Hasem Habelhah
    Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, NY, USA
    EMBO J 23:322-32. 2004
    ..Altogether, our findings highlight a novel mechanism of TRAF2-dependent activation of diverse signaling cascades that is impaired in Hodgkin-Reed-Sternberg cells...
  44. ncbi A role for Ubc9 in tumorigenesis
    Yin Yuan Mo
    Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA
    Oncogene 24:2677-83. 2005
    ..Together, these results suggest a role for Ubc9 in tumorigenesis at least partially through regulation of bcl-2 expression...
  45. pmc UbcH10 overexpression may represent a marker of anaplastic thyroid carcinomas
    P Pallante
    Dipartimento di Biologia e Patologia Cellulare e Molecolare c o Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Facoltà di Medicina e Chirurgia di Napoli, Universita degli Studi di Napoli Federico II, Italy
    Br J Cancer 93:464-71. 2005
    ..Taken together, these results would indicate that UbcH10 overexpression is involved in thyroid cell proliferation, and may represent a marker of thyroid anaplastic carcinomas...
  46. ncbi Transcriptional activity of peroxisome proliferator-activated receptor gamma is modulated by SUMO-1 modification
    Takayuki Ohshima
    Department of Viral Oncology, Institute for Virus Research, Kyoto University, Sakyo ku, Kyoto 606 8507, Japan
    J Biol Chem 279:29551-7. 2004
    ..These results suggest that the PPARgamma-dependent transactivation pathway seems to be modulated by SUMO-1 modification and may serve as a novel target for apoptosis-induction therapy in cancer cells...
  47. ncbi RAD6-RAD18-RAD5-pathway-dependent tolerance to chronic low-dose ultraviolet light
    Takashi Hishida
    Research Institute for Microbial Diseases, Osaka University, 3 1 Yamadaoka, Suita, Osaka 565 0871, Japan
    Nature 457:612-5. 2009
    ..Thus, the error-free PRR pathway is specifically important during chronic low-dose ultraviolet exposure to prevent counter-productive DNA checkpoint activation and allow cells to proliferate normally...
  48. ncbi Targeting Ubc9 for cancer therapy
    Yin Yuan Mo
    Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University, PO Box 19626, Springfield, IL 62794, USA
    Expert Opin Ther Targets 9:1203-16. 2005
    ....
  49. ncbi Essential role of E2-25K/Hip-2 in mediating amyloid-beta neurotoxicity
    Sungmin Song
    Department of Life Science, Kwangju Institute of Science and Technology, Kwangju 500 712, South Korea
    Mol Cell 12:553-63. 2003
    ..These results suggest that E2-25K/Hip-2 is a crucial factor in regulating Abeta neurotoxicity and could play a role in the pathogenesis of Alzheimer's disease...
  50. ncbi UbcH10 is overexpressed in malignant breast carcinomas
    Maria Teresa Berlingieri
    Dipartimento di Biologia e Patologia Cellulare e Molecolare c o Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Facoltà di Medicina e Chirurgia di Napoli, Universita degli Studi di Napoli Federico II, Via S Pansini 5, 80131 Naples, Italy
    Eur J Cancer 43:2729-35. 2007
    ..Therefore, these results suggest the perspective of a therapy of aggressive breast carcinomas based on the suppression of the UbcH10 function...
  51. ncbi Huntingtin is ubiquitinated and interacts with a specific ubiquitin-conjugating enzyme
    M A Kalchman
    Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4
    J Biol Chem 271:19385-94. 1996
    ..The huntingtin-E2-25K interaction is not obviously modulated by CAG length. We also demonstrate that huntingtin is ubiquitinated. These findings have implications for the regulated catabolism of the gene product for HD...
  52. pmc Der3p/Hrd1p is required for endoplasmic reticulum-associated degradation of misfolded lumenal and integral membrane proteins
    J Bordallo
    Institut fur Biochemie, Universitat Stuttgart, Germany
    Mol Biol Cell 9:209-22. 1998
    ..Der3p might serve as a component programming the translocon for retrograde transport of ER proteins, or it might be involved in recognition through its lumenal RING-H2 motif of proteins of the ER that are destined for degradation...
  53. ncbi E2-BRCA1 RING interactions dictate synthesis of mono- or specific polyubiquitin chain linkages
    Devin E Christensen
    Department of Biochemistry, University of Washington, Box 357350, Seattle, Washington 98195 7350, USA
    Nat Struct Mol Biol 14:941-8. 2007
    ..Thus, BRCA1 has the ability to direct the synthesis of specific polyubiquitin chain linkages, depending on the E2 bound to its RING...
  54. ncbi Identification of determinants in E2 ubiquitin-conjugating enzymes required for hect E3 ubiquitin-protein ligase interaction
    U Nuber
    Deutsches Krebsforschungszentrum, Angewandte Tumorvirologie, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany
    J Biol Chem 274:7576-82. 1999
    ..The conservation of this phenylalanine residue throughout evolution underlines the importance of the ability to interact with hect domain proteins for the cellular function of UBC4/UBC5 subfamily members...
  55. ncbi UbcH10 is the cancer-related E2 ubiquitin-conjugating enzyme
    Yoshiaki Okamoto
    Division of Biochemistry, Chiba Cancer Center Research Institute, Chiba 260 8717, Japan
    Cancer Res 63:4167-73. 2003
    ..Collectively, our present results provide the first evidence that UbcH10 is highly expressed in various human primary tumors and that UbcH10 has an ability to promote cell growth and malignant transformation...
  56. ncbi The nucleoporin RanBP2 has SUMO1 E3 ligase activity
    Andrea Pichler
    Max Planck Institute for Biochemistry, Am Klopferspitz 18a, 82152 Martinsried, Germany
    Cell 108:109-20. 2002
    ..Our findings place SUMOylation at the cytoplasmic filaments of the NPC and suggest that, at least for some substrates, modification and nuclear import are linked events...
  57. ncbi A proteolytic pathway that recognizes ubiquitin as a degradation signal
    E S Johnson
    Division of Biology, California Institute of Technology, Pasadena 91125, USA
    J Biol Chem 270:17442-56. 1995
    ....
  58. ncbi Ubiquitin-dependent proteolytic control of SUMO conjugates
    Kristina Uzunova
    Institute for Genetics, University of Cologne, Zulpicher Strasse 47, Cologne, Germany
    J Biol Chem 282:34167-75. 2007
    ..Simultaneous inhibition of both mechanisms leads to severe phenotypic defects...
  59. pmc Tsg101, a homologue of ubiquitin-conjugating (E2) enzymes, binds the L domain in HIV type 1 Pr55(Gag)
    L VerPlank
    Department of Molecular Genetics and Microbiology, State University of New York, Stony Brook, NY 11794 5222, USA
    Proc Natl Acad Sci U S A 98:7724-9. 2001
    ..The results link L-domain function in HIV to the Ub machinery and a specific component of the cellular trafficking apparatus...
  60. pmc RAD6-Mediated transcription-coupled H2B ubiquitylation directly stimulates H3K4 methylation in human cells
    Jaehoon Kim
    The Rockefeller University, New York, NY 10065, USA
    Cell 137:459-71. 2009
    ..These studies establish the natural H2B ubiquitylation factors in human cells and also detail the mechanistic basis for H2B ubiquitylation and function during transcription...
  61. ncbi A novel ubiquitination factor, E4, is involved in multiubiquitin chain assembly
    M Koegl
    Zentrum fur Molekulare Biologie, Universitat Heidelberg, Germany
    Cell 96:635-44. 1999
    ..In yeast, E4 activity is linked to cell survival under stress conditions, indicating that eukaryotes utilize E4-dependent proteolysis pathways for multiple cellular functions...
  62. pmc Different HECT domain ubiquitin ligases employ distinct mechanisms of polyubiquitin chain synthesis
    Min Wang
    Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
    EMBO J 24:4324-33. 2005
    ..A small region near the N-terminus of the conserved HECT domain helps to bring about this functional distinction. Thus, a given HECT domain can specify both the linkage of a polyubiquitin chain and the mechanism of its assembly...
  63. pmc The Rap80-BRCC36 de-ubiquitinating enzyme complex antagonizes RNF8-Ubc13-dependent ubiquitination events at DNA double strand breaks
    Genze Shao
    Department of Cancer Biology, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6160, USA
    Proc Natl Acad Sci U S A 106:3166-71. 2009
    ..These findings reveal a Rap80-BRCC36 dependent pathway that is required for appropriate DSB recruitment and repair responses...
  64. ncbi A conserved cysteine is essential for Pex4p-dependent ubiquitination of the peroxisomal import receptor Pex5p
    Chris Williams
    Department of Medical Biochemistry, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands
    J Biol Chem 282:22534-43. 2007
    ..Together, our results strongly suggest that Pex4p-dependent ubiquitination of Pex5p occurs on a cysteine residue...
  65. ncbi Structural basis for E2-mediated SUMO conjugation revealed by a complex between ubiquitin-conjugating enzyme Ubc9 and RanGAP1
    Victor Bernier-Villamor
    Biochemistry Department, Structural Biology Program, Weill Medical College of Cornell University, New York, NY 10021, USA
    Cell 108:345-56. 2002
    ..Structure-based mutagenesis and biochemical analysis of Ubc9 and RanGAP1 reveal distinct motifs required for substrate binding and SUMO modification of p53, IkappaBalpha, and RanGAP1...
  66. ncbi The Chfr mitotic checkpoint protein functions with Ubc13-Mms2 to form Lys63-linked polyubiquitin chains
    John Bothos
    The Wistar Institute, Philadelphia, PA 19104 4268, USA
    Oncogene 22:7101-7. 2003
    ..We propose that Chfr may have a role in signaling the presence of mitotic stress induced by microtubule poisons...
  67. ncbi The E2 ubiquitin-conjugating enzymes, AtUBC1 and AtUBC2, play redundant roles and are involved in activation of FLC expression and repression of flowering in Arabidopsis thaliana
    Lin Xu
    Institut de Biologie Moléculaire des plantes IBMP, Laboratoire Propre du CNRS UPR2357 conventionné avec l Université Louis Pasteur Strasbourg 1, 12 rue du Général Zimmer, 67084 Strasbourg Cedex, France
    Plant J 57:279-88. 2009
    ....
  68. ncbi A synergy control motif within the attenuator domain of CCAAT/enhancer-binding protein alpha inhibits transcriptional synergy through its PIASy-enhanced modification by SUMO-1 or SUMO-3
    Lalitha Subramanian
    Department of Pharmacology and Medical Scientist Training Program, University of Michigan Medical School, Ann Arbor, Michigan 48109 0632, USA
    J Biol Chem 278:9134-41. 2003
    ..Our results indicate that SUMO modification of SC motifs provides a means to rapidly control higher order interactions among transcription factors and suggests that SUMOylation may be a general mechanism to limit transcriptional synergy...
  69. ncbi Increased phosphorylation and dimethylation of XY body histones in the Hr6b-knockout mouse is associated with derepression of the X chromosome
    Willy M Baarends
    Department of Reproduction and Development, Erasmus MC University Medical Center, Rotterdam, The Netherlands
    J Cell Sci 120:1841-51. 2007
    ..We conclude that HR6B exerts control over different histone modifications in spermatocytes and spermatids, and that this function contributes to the postmeiotic maintenance of X chromosome silencing...
  70. ncbi Recognition of forked and single-stranded DNA structures by human RAD18 complexed with RAD6B protein triggers its recruitment to stalled replication forks
    Yuri Tsuji
    Cell Genetics, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan
    Genes Cells 13:343-54. 2008
    ..These results suggest that RAD18 complexed with RAD6B is recruited to stalled replication forks via interactions with forked DNA or long ssDNA structures, a process that is required for initiating PRR...
  71. pmc Insights into E3 ligase activity revealed by a SUMO-RanGAP1-Ubc9-Nup358 complex
    David Reverter
    Structural Biology Program, Sloan Kettering Institute, New York, New York 10021, USA
    Nature 435:687-92. 2005
    ....
  72. ncbi A UbcH5/ubiquitin noncovalent complex is required for processive BRCA1-directed ubiquitination
    Peter S Brzovic
    Department of Biochemistry, University of Washington, Seattle, 98195, USA
    Mol Cell 21:873-80. 2006
    ..Self-assembly has profound consequences for the processive formation of polyubiquitin (poly-Ub) chains in ubiquitination reactions directed by the breast and ovarian cancer tumor susceptibility protein BRCA1...
  73. pmc Ubc9 interacts with a nuclear localization signal and mediates nuclear localization of the paired-like homeobox protein Vsx-1 independent of SUMO-1 modification
    A L Kurtzman
    Department of Biochemistry and Cell Biology, State University of New York, Stony Brook, NY 11794, USA
    Proc Natl Acad Sci U S A 98:5602-7. 2001
    ..These results suggest that Ubc9 mediates the nuclear localization of Vsx-1, and possibly other proteins, through a nonenzymatic mechanism that is independent of SUMO-1 conjugation...
  74. ncbi SUMOylation regulates Rad18-mediated template switch
    Dana Branzei
    IFOM, the FIRC Institute for Molecular Oncology Foundation, IFOM IEO Campus, Via Adamello 16, 20139 Milan, Italy
    Nature 456:915-20. 2008
    ..Altogether, our results unmask a role for PCNA ubiquitylation and SUMOylation pathways in promoting transient damage-induced replication-coupled recombination events involving sister chromatids at replication forks...
  75. pmc Covalent modification of the androgen receptor by small ubiquitin-like modifier 1 (SUMO-1)
    H Poukka
    Department of Physiology, Institute of Biomedicine, and Department of Clinical Chemistry, University of Helsinki, FIN 00014, Helsinki, Finland
    Proc Natl Acad Sci U S A 97:14145-50. 2000
    ..Taken together, our data suggest that reversible sumoylation is a mechanism for regulation of steroid receptor function...
  76. ncbi Monoubiquitination of human histone H2B: the factors involved and their roles in HOX gene regulation
    Bing Zhu
    Howard Hughes Medical Institute, Division of Nucleic Acids Enzymology, Department of Biochemistry, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 683 Hoes Lane, Piscataway, New Jersey 08854, USA
    Mol Cell 20:601-11. 2005
    ..In contrast, RNAi against the RNF20/40 complex or hPAF complex reduces H2B monoubiquitination, lowers methylation levels at H3 lysines 4 and 79, and represses HOX gene expression...
  77. ncbi The Bur1/Bur2 complex is required for histone H2B monoubiquitination by Rad6/Bre1 and histone methylation by COMPASS
    Adam Wood
    Department of Biochemistry, Saint Louis University School of Medicine, 1402 South Grand Boulevard, St Louis, Missouri 63104, USA
    Mol Cell 20:589-99. 2005
    ..Our results identify in vivo substrates for Bur1/Bur2, thus linking its role to transcriptional elongation and demonstrating a potential activation mechanism for histone H2B monoubiquitination by the Rad6/Bre1 complex...
  78. ncbi Ubc9 is a novel modulator of the induction properties of glucocorticoid receptors
    Sunil Kaul
    Steroid Hormones Section, NIDDK Laboratory of Molecular and Cellular Biology, National Institutes of Health, Bethesda, MD 20892, USA
    J Biol Chem 277:12541-9. 2002
    ..With high concentrations of Ubc9 and GR, Ubc9 binding to GR appears to be sufficient to permit Ubc9 to act independently of the GME...
  79. ncbi Sequential E2s drive polyubiquitin chain assembly on APC targets
    Monica C Rodrigo-Brenni
    Department of Physiology, University of California, San Francisco, CA 94158, USA
    Cell 130:127-39. 2007
    ..E2-25K, a human homolog of Ubc1, also promotes APC-dependent chain extension on preattached ubiquitins. We propose that sequential E2 proteins catalyze K48-linked polyubiquitination and thus proteasomal destruction of APC targets...
  80. pmc UBE2S elongates ubiquitin chains on APC/C substrates to promote mitotic exit
    Mathew J Garnett
    University of Cambridge, Department of Oncology and The Medical Research Council Cancer Cell Unit, Hutchison MRC Research Centre, Hills Road, Cambridge, CB2 OXZ, UK
    Nat Cell Biol 11:1363-9. 2009
    ..Thus, UBE2S functions with the APC/C in a two-step mechanism to control substrate ubiquitylation that is essential for mitotic exit after prolonged SAC activation, providing a new model for APC/C function in human cells...
  81. ncbi The SUMO pathway is essential for nuclear integrity and chromosome segregation in mice
    Karim Nacerddine
    Unité d Organisation Nucléaire et Oncogénèse, INSERM U 579, Institut Pasteur, 75724 Paris Cedex 15, France
    Dev Cell 9:769-79. 2005
    ..Together, these findings reveal a major role for Ubc9, and, by implication, for the SUMO pathway, in nuclear architecture and function, chromosome segregation, and embryonic viability in mammals...
  82. pmc Structure of the anaphase-promoting complex/cyclosome interacting with a mitotic checkpoint complex
    Franz Herzog
    Research Institute of Molecular Pathology, Dr Bohr Gasse 7, 1030 Vienna, Austria
    Science 323:1477-81. 2009
    ..These observations clarify the structural basis for the inhibition of APC/C by spindle checkpoint proteins...
  83. ncbi The processivity of multiubiquitination by the APC determines the order of substrate degradation
    Michael Rape
    Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
    Cell 124:89-103. 2006
    ..The processivity of multiubiquitination is strongly influenced by the D box within the substrate, suggesting that substrate ordering is established by a mechanism intrinsic to APC and its substrates and similar to kinetic proofreading...
  84. ncbi Two different classes of E2 ubiquitin-conjugating enzymes are required for the mono-ubiquitination of proteins and elongation by polyubiquitin chains with a specific topology
    Mark Windheim
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Biochem J 409:723-9. 2008
    ....
  85. ncbi Noncanonical MMS2-encoded ubiquitin-conjugating enzyme functions in assembly of novel polyubiquitin chains for DNA repair
    R M Hofmann
    Department of Biochemistry, School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA
    Cell 96:645-53. 1999
    ..These findings support a model in which an Mms2p/Ubc13p complex assembles novel polyubiquitin chains for signaling in DNA repair, and they suggest that UEV proteins may act to increase diversity and selectivity in ubiquitin conjugation...
  86. ncbi SAGE and antibody array analysis of melanoma-infiltrated lymph nodes: identification of Ubc9 as an important molecule in advanced-stage melanomas
    S J Moschos
    Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213 1863, USA
    Oncogene 26:4216-25. 2007
    ....
  87. ncbi Expression of ubiquitin-conjugating enzyme E2C/UbcH10 in astrocytic tumors
    Lei Jiang
    Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China
    Brain Res 1201:161-6. 2008
    ..63, p<0.001). These data suggest that overexpression of UbcH10 may serve as one important molecular mechanism that underlies the astrocytic carcinogenesis...
  88. pmc Synthesis of free and proliferating cell nuclear antigen-bound polyubiquitin chains by the RING E3 ubiquitin ligase Rad5
    Candice M Carlile
    Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA
    J Biol Chem 284:29326-34. 2009
    ..These findings indicate that Rad5-mediated recognition of monoUb-PCNA in vivo is likely to depend upon interactions with additional factors at stalled replication forks...
  89. ncbi Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast
    Zu Wen Sun
    Department of Biochemistry and Molecular Genetics, University of Virginia Health System, Charlottesville, Virginia 22908 0733, USA
    Nature 418:104-8. 2002
    ..We refer to this as 'trans-tail' regulation of histone modification, a stated prediction of the histone code hypothesis...
  90. ncbi Polymeric chains of SUMO-2 and SUMO-3 are conjugated to protein substrates by SAE1/SAE2 and Ubc9
    M H Tatham
    Institute of Biomolecular Sciences, University of St Andrews, North Haugh, St Andrews KY16 5ST, United Kingdom
    J Biol Chem 276:35368-74. 2001
    ..The ability to form polymeric chains is not shared by SUMO-1, and although all SUMO species use the same conjugation machinery, modification by SUMO-1 and SUMO-2/-3 may have distinct functional consequences...
  91. ncbi Control of spontaneous and damage-induced mutagenesis by SUMO and ubiquitin conjugation
    Philipp Stelter
    Max Planck Institute for Terrestrial Microbiology, Karl von Frisch Strasse, 35043 Marburg, Germany
    Nature 425:188-91. 2003
    ..Our findings assign a function to SUMO during S phase and demonstrate how ubiquitin and SUMO, by regulating the accuracy of replication and repair, contribute to overall genomic stability...
  92. pmc MicroRNA-mediated regulation of Ubc9 expression in cancer cells
    Fangting Wu
    Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, Illinois 62794, USA
    Clin Cancer Res 15:1550-7. 2009
    ..The aim of this study was to investigate the regulation of Ubc9 in cancer cells...
  93. ncbi The tyrosine kinase negative regulator c-Cbl as a RING-type, E2-dependent ubiquitin-protein ligase
    C A Joazeiro
    The Salk Institute, Molecular Biology and Virology Laboratory, La Jolla, CA 92037, USA
    Science 286:309-12. 1999
    ..These results reveal an SH2-containing protein that functions as a ubiquitin-protein ligase and thus provide a distinct mechanism for substrate targeting in the ubiquitin system...
  94. pmc Contributions of ubiquitin- and PCNA-binding domains to the activity of Polymerase eta in Saccharomyces cerevisiae
    Joanne L Parker
    Cancer Research UK, London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, EN6 3LD, United Kingdom
    Nucleic Acids Res 35:881-9. 2007
    ..Like its mammalian homolog, budding yeast Polymerase eta itself is ubiquitylated in a manner dependent on its ubiquitin-binding domain...
  95. pmc Anatomy of the E2 ligase fold: implications for enzymology and evolution of ubiquitin/Ub-like protein conjugation
    A Maxwell Burroughs
    National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA
    J Struct Biol 162:205-18. 2008
    ..These features are likely to form a critical mechanical element of the fold required for catalysis. The results presented here could aid in new experiments to understand E2 catalysis...
  96. ncbi Up-regulation of CIR1/CROC1 expression upon cell immortalization and in tumor-derived human cell lines
    L Ma
    Department of Pathology, McMaster University, Hamilton, Ontario, Canada
    Oncogene 17:1321-6. 1998
    ..These results are compatible with induction of CIR1/CROC1 being an early event in the acquisition of immortality and with a role for this gene in the immortal phenotype of tumor cells...
  97. ncbi Cloning of human ubiquitin-conjugating enzymes UbcH6 and UbcH7 (E2-F1) and characterization of their interaction with E6-AP and RSP5
    U Nuber
    Deutsches Krabsforschungszentrum, Angewandte Tumorvirologie, Heidelberg, Federal Republic of Germany
    J Biol Chem 271:2795-800. 1996
    ..In addition, UbcH5 but not UbcH6 or UbcH7 efficiently interacts with the heet protein RSP5. These results indicate that E6-AP can interact with at least two species of E2 and that different hect proteins may interact with different E2s...
  98. pmc Dysfunction of human Rad18 results in defective postreplication repair and hypersensitivity to multiple mutagens
    S Tateishi
    Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Kumamoto 862 0976, Japan
    Proc Natl Acad Sci U S A 97:7927-32. 2000
    ..Stable transformants with hRad18 mutated in this motif become sensitive to UV, methyl methanesulfonate, and mitomycin C, and are defective in the replication of UV-damaged DNA. Thus, hRAD18 is a functional homologue of RAD18...
  99. ncbi A novel role for N-glycans in the ERAD system
    Yukiko Yoshida
    Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, 3 18 22 Honkomagome, Bunkyo ku, Tokyo 113 8613
    J Biochem 134:183-90. 2003
    ..In this review, I describe recent advances in the molecular basis of the ERAD system, particularly those mediated by N-glycan recognition molecules...
  100. ncbi Structural and functional conservation of error-free DNA postreplication repair in Schizosaccharomyces pombe
    Morgan Brown
    Department of Microbiology and Immunology, University of Saskatchewan, Saskatoon, Canada
    DNA Repair (Amst) 1:869-80. 2002
    ..Hence, our data strongly support the hypothesis that the PRR function mediated by UBC13-MMS2 is conserved throughout eukaryotes...
  101. ncbi The UBA domain: a sequence motif present in multiple enzyme classes of the ubiquitination pathway
    K Hofmann
    Swiss Institute for Experimental Cancer Research, Epalinges s Lausanne, Switzerland
    Trends Biochem Sci 21:172-3. 1996

Research Grants52

  1. 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...
  2. Cullin mediated protein turnover in skeletal and cardiac muscles
    Stephan Lange; Fiscal Year: 2012
    ..and its subsequent ubiquitylation involves the concerted action of E3-ubiquitin ligases and E2-ubiquitin conjugating enzymes. Intriguingly, several components involved in the ubiquitylation of muscle proteins are localized ..
  3. Cullin mediated protein turnover in skeletal and cardiac muscles
    Stephan Lange; Fiscal Year: 2013
    ..and its subsequent ubiquitylation involves the concerted action of E3-ubiquitin ligases and E2-ubiquitin conjugating enzymes. Intriguingly, several components involved in the ubiquitylation of muscle proteins are localized ..
  4. Ubiquitination in erythropoiesis and the pathophysiology of anemia
    Mark D Fleming; Fiscal Year: 2013
    ....
  5. Structural Biology of U-box E3 Ubiquitin Ligases
    Walter J Chazin; Fiscal Year: 2013
    ..Despite the availability of structures of CHIP, E2 ubiquitin conjugating enzymes and heat shock proteins, the factors controlling the selection of ubiquitination sites on the ..
  6. Role of the SCF/Fbxo15 ubiquitin ligase in stem cells and cancer biology
    Michele Pagano; Fiscal Year: 2012
    ..e. ubiquitin conjugating enzymes and ubiquitin ligases) and protein degradation (i.e. the proteasome)...
  7. High throughput screening for modulators of UBC12
    MATTHEW PETROSKI; Fiscal Year: 2013
    ....
  8. MOLECULAR CONTROL OF CELL PROLIFERATION
    DAVID OWEN MORGAN; Fiscal Year: 2010
    ..These studies are also likely to illuminate general mechanisms of protein ubiquitination, a regulatory modification of importance throughout cell biology and human disease. ..
  9. 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)...
  10. Global Approaches to Protein Ubiquitylation
    Dieter A Wolf; Fiscal Year: 2010
    ..A more detailed understanding of the exact pathways and substrates controlled by ubiquitylation enzymes such as enabled by the studies proposed in this application will be required to harness the full potential of such efforts. ..
  11. Quantitative Analysis of RING E3 Ubiquitin Ligases
    CHARLES M BRENNER; Fiscal Year: 2010
    ..2003;Kirkpatrick et al., 2005a). Third, the E2 ubiquitin conjugating enzymes have different specificities and potentially form different sets of target protein and polyubiquitin ..
  12. MOLECULAR CONTROL OF CELL PROLIFERATION
    DAVID OWEN MORGAN; Fiscal Year: 2013
    ..These studies are also likely to illuminate general mechanisms of protein ubiquitination, a regulatory modification of major importance throughout cell biology and human disease. ..
  13. Analysis of CHIP, a ubiquitin ligase implicated in neurodegeneration
    KENNETH MATTHEW SCAGLIONE; Fiscal Year: 2010
    ..regulate the types of ubiquitin chain linkages formed by CHIP;tested candidates will include all known ubiquitin conjugating enzymes (E2s) as well as a panel of selected de ubiquitinating enzymes (DUBs) and Ubiquitin Interacting Motif-..
  14. Immune evasion by gamma 2 Herpesviruses
    KLAUS J FRUEH; Fiscal Year: 2010
    ..abstract_text> ..
  15. The role of UBE2V1 in HIV-1 restriction in primary monocytes
    Li Wu; Fiscal Year: 2013
    ..Ultimately, the knowledge learned from the proposed studies will enable design of novel approaches to block HIV-1 replication in target cells. ..
  16. Unconventional Interactions of Human Ubiquitin Conjugating Enzymes
    Peter S Brzovic; Fiscal Year: 2013
    ..The new knowledge we seek to obtain will have a significant impact our understanding of human E2 structure and function and greatly accelerate biological research involving ubiquitylation and ubiquitin signaling. ..
  17. NUCLEAR HORMONE ACTION--ROLE OF UBIQUITIN PATHWAYS
    Zafar Nawaz; Fiscal Year: 2003
    ..Of the NEDD8 pathway as a co-activator of NHRs and to characterize this role in nuclear hormone receptor co-activation. ..
  18. Identifying Ubiquitin E3 Substrates with Redesigned E3s
    Brian Kuhlman; Fiscal Year: 2005
    ..Favorable results will indicate that this new method should be an excellent approach for identifying substrates of other E3 ubiquitin ligases important to health and disease. ..
  19. ROLES OF UBIQUITIN CONJUGATING ENZYMES IN DNA REPAIR
    Zhiyuan Shen; Fiscal Year: 2001
    ....
  20. FASEB CONFERENCE ON UBIQUITIN AND PROTEIN DEGRADATION
    George Demartino; Fiscal Year: 2001
    ..The small size of the conference, and its location and format are designed to foster maximal interactions among the 175 participants. ..
  21. REGULATION OF GROWTH ARREST IN HYPEROXIC NEONATAL LUNG
    Sharon McGrath Morrow; Fiscal Year: 2001
    ..growth arrest secondary to hyperoxia in the neonatal lung is associated with the down regulation of ubiquitin conjugating enzymes necessary for the degradation of specific cyclin inhibitors...
  22. UBIQUITIN-MEDIATED CIRCUITRY IN GENOMIC INTEGRITY
    Yong Wan; Fiscal Year: 2006
    ..Genetic and biochemical studies in yeast and mammals have demonstrated that several ubiquitin conjugating enzymes and ubiquitin protein ligases including Ube2A, Ube2B, Ube2rE, Ube2N, BRCA1/BARD1, CDH1/APC are ..
  23. BIOCHEMISTRY OF UBIQUITIN-CONJUGATING ENZYMES
    Vincent Chau; Fiscal Year: 2004
    ..He expects that the biochemical analysis will provide important mechanistic insights and the prerequisite information for the evaluation of this pathway for potential therapeutic intervention. ..
  24. Degradation of ABC transporters in genetic liver disease
    Lin Wang; Fiscal Year: 2006
    ..III) Examine the ERAD-specific ubiquitin conjugating enzymes in the degradation of the BSEP mutants...
  25. STRUCTURE/FUNCTION OF UBIQUITIN CONJUGATING ENZYMES
    Vincent Chau; Fiscal Year: 1999
    ....
  26. FUNCTION OF AN INTERFERON INDUCED UBIQUITIN HOMOLOG
    Arthur Haas; Fiscal Year: 2003
    ..kDa polypeptides bear remarkable yet cryptic sequence similarity to the conserved catalytic domain of ubiquitin conjugating enzymes (Ubc). The present proposal comprises three specific aims...
  27. MECHANISMS OF SIGNAL INDUCED UBIQUITINATION OF IKBA
    Zhijian Chen; Fiscal Year: 2002
    ..abstract_text> ..
  28. Ubc9 as a novel target for cancer therapy
    Yin Yuan Mo; Fiscal Year: 2006
    ..As a result, we will be able to develop valuable Ubc9-based anticancer agents [unreadable] [unreadable]..
  29. Substrates of SAG-SCF E3 ligase regulate hypoxia response
    Yi Sun; Fiscal Year: 2007
    ..These initial studies will set the stage for a more detailed investigation of the mechanism of SAG mediated suppression of apoptosis. [unreadable] [unreadable]..
  30. SAG E3 ubiquitin ligase in angiogenesis & carcinogenesis
    Yi Sun; Fiscal Year: 2010
    ..Targeting SAG in cancer cells, via siRNA silencing or small molecule inhibitors, would, therefore, be a valid antianglogenesis therapy. ..
  31. Chromatin Regulation of Double-Strand Break Repair
    Mary Ann Osley; Fiscal Year: 2010
    ..The studies are significant because they will reveal new regulatory mechanisms in DSB repair, and thus identify new targets to exploit in cancer radio- and chemotherapy. ..
  32. ACTIVATION OF IKB KINASE BY HTLV-I TAX
    Shao Cong Sun; Fiscal Year: 2003
    ..abstract_text> ..
  33. Role of ubiquitin in quality control of lens proteins
    Fu Shang; Fiscal Year: 2010
    ..The proposed work will increase our knowledge of how the lens maintains its transparent function and will potentially identify targets of pharmaceutical interventions for prevention or treatment of age-related cataract. ..
  34. Myocyte signaling and the response to stress
    WINSTON PATTERSON; Fiscal Year: 2009
    ....
  35. 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. ..
  36. REPAIR OF DNA DAMAGED BY UV IRRADIATION IN YEAST
    Louise Prakash; Fiscal Year: 2003
    ..The DNA replication/damage bypass proteins which become ubiquitinated in response to DNA damage will be identified, and the role of RAD6 and RAD18 in this process will be determined. ..
  37. DNA SEQUENCING OF UV INDUCED CHROMOSOMAL MUTATIONS
    Christopher Lawrence; Fiscal Year: 2003
    ..abstract_text> ..
  38. Aging, Stress and Atherosclerosis
    WINSTON PATTERSON; Fiscal Year: 2003
    ..Based on these studies, we will create molecular portraits of the ROS-dependent and ROS-independent transcripts preferentially associated with aging. ..
  39. MECHANISM OF TRANSLESION REPLICATION IN EUKARYOTES
    Christopher Lawrence; Fiscal Year: 2003
    ..These plasmids have proved useful in detecting different kinds of recombinant events, a likely mechanism for the pathway. ..
  40. THE S. CEREVISIAE S PHASE CHECKPOINT
    Steven Reed; Fiscal Year: 2003
    ....
  41. Intracellular targeting of HIV Gag proteins
    ROBERT WELDON; Fiscal Year: 2005
    ..The results obtained from these studies will provide important information about how Gag proteins function within cells and may provide a framework for developing novel therapeutic strategies to combat HIV replication. ..
  42. HBF VARIANTS FOR GENE THERAPY OF SICKLE CELL DISEASE
    Kazuhiko Adachi; Fiscal Year: 2005
    ....
  43. Carolina Cardiopulmonary Gene Expression Services
    WINSTON PATTERSON; Fiscal Year: 2005
    ..abstract_text> ..
  44. Gene Therapy of Muscle Wasting From Uremia
    Xiaonan Wang; Fiscal Year: 2005
    ..We believe that the experimental results will shed the insight on the mechanisms of muscle protein degradation, and provide a possible new approach to treat the pathological process of muscle wasting. ..
  45. Repair Pathways for Ionizing Radiation Damage Yeast
    John Game; Fiscal Year: 2006
    ..Recent and existing mutants will be studied in detail with this system to determine the molecular involvement of each gene in DSB repair, sister chromatid exchange and recombination between chromosomes. ..
  46. The Role of Dystroglycan in Signal Transduction
    Hannele Ruohola Baker; Fiscal Year: 2007
    ..This research will advance the understanding of DG function in signal transduction and how it is regulated to mediate different intracellular pathways. [unreadable] [unreadable]..
  47. ROLE OF PROTEASOMAL DYSFUNCTION IN PARKINSON'S DISEASE
    KEVIN MCNAUGHT; Fiscal Year: 2008
    ..These studies will test our hypothesis that inadequate proteasomal function underlies both vulnerability and degeneration of the SNc in sporadic Parkinson's disease. ..
  48. ROLE OF NOTCH PATHWAY IN DROSOPHILA OOGENESIS
    Hannele Ruohola Baker; Fiscal Year: 2008
    ..In both cases we seek first to understand how the key regulators get activated for the purpose of cell cycle regulation and second, how the canonical pathways impact the cell cycle machinery. ..
  49. Molecular Mechanisms Mediating NF-kB2/p100 Processing
    Shao Cong Sun; Fiscal Year: 2007
    ..abstract_text> ..
  50. Single Cell Analysis of Cross Talk Among Kinase Pathways
    Stefan Kaluz; Fiscal Year: 2008
    ..These studies will provide additional information relating to our understanding of the consequencesof activationof kinase signaling pathwayswith respect to malignant transformation, aggressive tumor growth and survival. ..
  51. The role of Cyclin E in growth control and tumorogenesis
    Steven Reed; Fiscal Year: 2008
    ..It is hoped that insights gained from understanding these fundamental mechanisms of oncogenesis will lead to new approaches to cancer prevention and therapy. ..
  52. NIK KINASE AND T CELL COSTIMULATION
    Shao Cong Sun; Fiscal Year: 2003
    ..It is also expected that novel signaling molecules will have been isolated which function in the T cell co-stimulatory pathway. ..