A Ciechanover

Summary

Affiliation: Technion-Israel Institute of Technology
Country: Israel

Publications

  1. pmc The ubiquitin-proteasome pathway: on protein death and cell life
    A Ciechanover
    Department of Biochemistry, The Bruce Rappaport Faculty of Medicine, Technion Israel Institute of Technology, P O Box 9649, Efron Street, Bat Galim, Haifa 31096
    EMBO J 17:7151-60. 1998
  2. pmc Degradation of the proto-oncogene product c-Fos by the ubiquitin proteolytic system in vivo and in vitro: identification and characterization of the conjugating enzymes
    I Stancovski
    Department of Biochemistry, Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel
    Mol Cell Biol 15:7106-16. 1995
  3. pmc SCF(beta)(-TrCP) ubiquitin ligase-mediated processing of NF-kappaB p105 requires phosphorylation of its C-terminus by IkappaB kinase
    A Orian
    Department of Biochemistry and the Rappaport Institute for Research in the Medical Sciences, The Bruce Rappaport Faculty of Medicine, Haifa 31096, Israel
    EMBO J 19:2580-91. 2000
  4. ncbi request reprint Degradation of the tumor suppressor protein p53 by the ubiquitin-mediated proteolytic system requires a novel species of ubiquitin-carrier protein, E2
    A Ciechanover
    Department of Biochemistry, Faculty of Medicine, Technion Israel Institute of Technology, Haifa
    J Biol Chem 269:9582-9. 1994
  5. ncbi request reprint Processing of p105 is inhibited by docking of p50 active subunits to the ankyrin repeat domain, and inhibition is alleviated by signaling via the carboxyl-terminal phosphorylation/ ubiquitin-ligase binding domain
    S Cohen
    Department of Biochemistry and the Rappaport Family Institute for Research in the Medical Sciences, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel
    J Biol Chem 276:26769-76. 2001
  6. ncbi request reprint Modes of regulation of ubiquitin-mediated protein degradation
    D Kornitzer
    Department of Molecular Microbiology, The Bruce Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel
    J Cell Physiol 182:1-11. 2000
  7. pmc Degradation of nuclear oncoproteins by the ubiquitin system in vitro
    A Ciechanover
    Department of Biochemistry, Faculty of Medicine, Technion Israel Institute of Technology, Haifa
    Proc Natl Acad Sci U S A 88:139-43. 1991
  8. ncbi request reprint Intracellular protein degradation: from a vague idea thru the lysosome and the ubiquitin-proteasome system and onto human diseases and drug targeting
    A Ciechanover
    Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Haifa 31096, Israel
    Cell Death Differ 12:1178-90. 2005
  9. pmc Structural motifs involved in ubiquitin-mediated processing of the NF-kappaB precursor p105: roles of the glycine-rich region and a downstream ubiquitination domain
    A Orian
    Department of Biochemistry and Rappaport Family Institute for Research in the Medical Sciences, The Bruce Rappaport Faculty of Medicine, Haifa 31096, Israel
    Mol Cell Biol 19:3664-73. 1999
  10. ncbi request reprint Ubiquitin-mediated proteolysis: biological regulation via destruction
    A Ciechanover
    Department of Biochemistry, The Bruce Rappaport Faculty of Medicine and the Rappaport Family Institute for Research in the Medical Sciences, Technion Israel Institute of Technology, Israel
    Bioessays 22:442-51. 2000

Collaborators

  • A L Schwartz
  • J D Richter
  • M Oren
  • F Mercurio
  • C Kahana
  • T M Thomson
  • A Varshavsky
  • A Valencia
  • Toshihisa Ishikawa
  • A Orian
  • H Gonen
  • K Iwai
  • B Bercovich
  • G Melino
  • L Sun
  • J S Trausch-Azar
  • S Cohen
  • A Israel
  • K Breitschopf
  • N Gupta-Rossi
  • A Hengstermann
  • Z E Floyd
  • R Amir
  • R V Sionov
  • E Sadot
  • E Reinstein
  • D Kornitzer
  • R Knight
  • G Levkowitz
  • G Browne
  • F Scialpi
  • R I Aqeilan
  • M Rossi
  • F Bernassola
  • C J Cummings
  • A Peschiaroli
  • L Zocchi
  • E Gallagher
  • M Malatesta
  • E Sancho
  • O Staub
  • A G Stephen
  • Y Haupt
  • L K Linares
  • S Coen
  • E Six
  • F Logeat
  • O Le Bail
  • N J Whitaker
  • Z Goldberg
  • C Brou
  • M Scheffner
  • Y Ben-Neriah
  • M Berger
  • I Fajerman
  • A Ben-Ze'ev
  • I Stancovski
  • E Eytan
  • I Simcha
  • B Geiger
  • Y Sun
  • A L Beaudet
  • Y Yarden
  • M Katz
  • H Y Zoghbi
  • H T Orr
  • I Alroy
  • K Yamanaka
  • C Takizawa
  • Y Reiss
  • H Waterman
  • B Antalffy
  • Y Jiang
  • S Whiteside
  • M Pagano
  • A Y Tsygankov
  • S A Ettenberg
  • A Carrano
  • S Lavi
  • S Lipkowitz
  • S L Lin
  • C Harvey
  • E Bengal
  • R Paciucci
  • F Sanz
  • N Blumenfeld
  • J J Lozano
  • X Estivill
  • A Admon
  • N Loukili

Detail Information

Publications33

  1. pmc The ubiquitin-proteasome pathway: on protein death and cell life
    A Ciechanover
    Department of Biochemistry, The Bruce Rappaport Faculty of Medicine, Technion Israel Institute of Technology, P O Box 9649, Efron Street, Bat Galim, Haifa 31096
    EMBO J 17:7151-60. 1998
  2. pmc Degradation of the proto-oncogene product c-Fos by the ubiquitin proteolytic system in vivo and in vitro: identification and characterization of the conjugating enzymes
    I Stancovski
    Department of Biochemistry, Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel
    Mol Cell Biol 15:7106-16. 1995
    ..Taken together, our in vivo and in vitro studies strongly suggest that c-Fos is degraded in the cell by the ubiquitin-proteasome proteolytic pathway in a process that requires a novel recognition enzyme...
  3. pmc SCF(beta)(-TrCP) ubiquitin ligase-mediated processing of NF-kappaB p105 requires phosphorylation of its C-terminus by IkappaB kinase
    A Orian
    Department of Biochemistry and the Rappaport Institute for Research in the Medical Sciences, The Bruce Rappaport Faculty of Medicine, Haifa 31096, Israel
    EMBO J 19:2580-91. 2000
    ..Since p105-Delta918-934 is also conjugated and processed, it appears that p105 can be recognized under different physiological conditions by two different ligases, targeting two distinct recognition motifs...
  4. ncbi request reprint Degradation of the tumor suppressor protein p53 by the ubiquitin-mediated proteolytic system requires a novel species of ubiquitin-carrier protein, E2
    A Ciechanover
    Department of Biochemistry, Faculty of Medicine, Technion Israel Institute of Technology, Haifa
    J Biol Chem 269:9582-9. 1994
    ....
  5. ncbi request reprint Processing of p105 is inhibited by docking of p50 active subunits to the ankyrin repeat domain, and inhibition is alleviated by signaling via the carboxyl-terminal phosphorylation/ ubiquitin-ligase binding domain
    S Cohen
    Department of Biochemistry and the Rappaport Family Institute for Research in the Medical Sciences, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel
    J Biol Chem 276:26769-76. 2001
    ..Following stimulation, the C-terminal domain is involved in rapid processing/degradation of p105 with release of a large amount of the stored subunits that now become transcriptionally active...
  6. ncbi request reprint Modes of regulation of ubiquitin-mediated protein degradation
    D Kornitzer
    Department of Molecular Microbiology, The Bruce Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel
    J Cell Physiol 182:1-11. 2000
    ..Here, we review the basic mechanisms of the ubiquitin system and the various ways in which ubiquitin-mediated degradation can be modulated by physiological signals...
  7. pmc Degradation of nuclear oncoproteins by the ubiquitin system in vitro
    A Ciechanover
    Department of Biochemistry, Faculty of Medicine, Technion Israel Institute of Technology, Haifa
    Proc Natl Acad Sci U S A 88:139-43. 1991
    ..Furthermore, the relative sensitivity to degradation of various E1A mutants in vivo is also maintained in the cell-free system, suggesting that the ubiquitin pathway may play a role in the cellular degradation of these proteins as well...
  8. ncbi request reprint Intracellular protein degradation: from a vague idea thru the lysosome and the ubiquitin-proteasome system and onto human diseases and drug targeting
    A Ciechanover
    Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Haifa 31096, Israel
    Cell Death Differ 12:1178-90. 2005
    ..Not surprisingly, aberrations in the system have been implicated in the pathogenesis of human disease, such as malignancies and neurodegenerative disorders, which led subsequently to an increasing effort to develop mechanism-based drugs...
  9. pmc Structural motifs involved in ubiquitin-mediated processing of the NF-kappaB precursor p105: roles of the glycine-rich region and a downstream ubiquitination domain
    A Orian
    Department of Biochemistry and Rappaport Family Institute for Research in the Medical Sciences, The Bruce Rappaport Faculty of Medicine, Haifa 31096, Israel
    Mol Cell Biol 19:3664-73. 1999
    ..In particular, both Lys 441 and Lys 442 appear to serve as major ubiquitination targets, while residues 446 to 454 are independently important for processing and may serve as the ubiquitin ligase recognition motif...
  10. ncbi request reprint Ubiquitin-mediated proteolysis: biological regulation via destruction
    A Ciechanover
    Department of Biochemistry, The Bruce Rappaport Faculty of Medicine and the Rappaport Family Institute for Research in the Medical Sciences, Technion Israel Institute of Technology, Israel
    Bioessays 22:442-51. 2000
    ..Substrate recognition is governed by a large family ubiquitin ligases that recognize the substrates, bind them and catalyze/facilitate their interaction with ubiquitin...
  11. ncbi request reprint Ubiquitin-mediated degradation of cellular proteins: why destruction is essential for construction, and how it got from the test tube to the patient's bed
    A Ciechanover
    Department of Biochemistry, Bruce Rappaport Faculty of Medicine and Rappaport Family Institute for Research in the Medical Sciences, Technion Israel Institute of Technology, Haifa, Israel
    Isr Med Assoc J 3:319-27. 2001
    ..Among these are the modes of specific and timed recognition of the myriad substrates of the system and the nature of the mechanisms that underlie aberrations in the system and pathogenesis of diseases...
  12. ncbi request reprint The ubiquitin proteolytic system and pathogenesis of human diseases: a novel platform for mechanism-based drug targeting
    A Ciechanover
    Department of Biochemistry, The Bruce Rappaport Faculty of Medicine and the Rappaport Family Institute for Research in the Medical Sciences, Technion Israel Institute of Technology, Haifa 31096, Israel
    Biochem Soc Trans 31:474-81. 2003
    ....
  13. ncbi request reprint Purification and characterization of a novel species of ubiquitin-carrier protein, E2, that is involved in degradation of non-"N-end rule" protein substrates
    N Blumenfeld
    Department of Biochemistry, Faculty of Medicine, Technion Israel Institute of Technology, Haifa
    J Biol Chem 269:9574-81. 1994
    ..The enzyme is also involved in the conjugation and degradation of the tumor suppressor protein p53...
  14. ncbi request reprint Functional interaction between SEL-10, an F-box protein, and the nuclear form of activated Notch1 receptor
    N Gupta-Rossi
    Unité de Biologie Moléculaire de l Expression Génique, FRE 2364, CNRS, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France
    J Biol Chem 276:34371-8. 2001
    ..Taken together, these data suggest that SEL-10 is involved in shutting off Notch signaling by ubiquitin-proteasome-mediated degradation of the active transcriptional factor after a nuclear phosphorylation event...
  15. ncbi request reprint Differential interaction of plakoglobin and beta-catenin with the ubiquitin-proteasome system
    E Sadot
    Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel
    Oncogene 19:1992-2001. 2000
    ....
  16. ncbi request reprint The ubiquitin-dependent proteolytic pathway: specificity of recognition of the proteolytic substrates
    A Ciechanover
    Department of Biochemistry, Rappaport Institute for Research in Medical Sciences, Haifa, Israel
    Revis Biol Celular 20:217-34. 1989
    ..The scope of this review is to discuss recent developments in our understanding of the specificity and selection of substrates for conjugation and subsequent degradation via the ubiquitin system...
  17. ncbi request reprint Mutation of the E6-AP ubiquitin ligase reduces nuclear inclusion frequency while accelerating polyglutamine-induced pathology in SCA1 mice
    C J Cummings
    Program in Cell and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Neuron 24:879-92. 1999
    ..Taken together, NIs are not necessary to induce neurodegeneration, but impaired proteasomal degradation of mutant ataxin-1 may contribute to SCA1 pathogenesis...
  18. ncbi request reprint Thermolability of ubiquitin-activating enzyme from the mammalian cell cycle mutant ts85
    D Finley
    Cell 37:43-55. 1984
    ..We discuss possible roles of ubiquitin-dependent pathways in DNA transactions, the cell cycle, and the heat shock response...
  19. ncbi request reprint The nuclear ubiquitin-proteasome system degrades MyoD
    Z E Floyd
    Edward Mallinckrodt Department of Pediatrics and Molecular Biology and Pharmacology, Washington University School of Medicine, and Division of Pediatric Hematology-Oncology, St. Louis Children's Hospital, St. Louis, Missouri 63110, USA
    J Biol Chem 276:22468-75. 2001
    ..In addition, in vivo studies, using leptomycin B to inhibit nuclear export, demonstrate that MyoD is degraded in HeLa cells by the nuclear ubiquitin-proteasome system...
  20. ncbi request reprint [The ubiquitin-proteasome system: the relationship between protein degradation and human diseases]
    R Amir
    Department of Biochemistry, Faculty of Medicine Baruch Rappaport, Research Institute in Medical Sciences Rappaport, Technion, Department of Internal Medicine A, Carmel Medical Center, Haifa, Israel
    Harefuah 140:1172-6, 1229. 2001
    ....
  21. pmc Regulation of stability and function of the epithelial Na+ channel (ENaC) by ubiquitination
    O Staub
    Hospital for Sick Children, Division of Respiratory Research, Toronto, Ontario, Canada
    EMBO J 16:6325-36. 1997
    ..Our results suggest that ENaC function is regulated by ubiquitination, and propose a paradigm for ubiquitination-mediated regulation of ion channels...
  22. ncbi request reprint E2A protein degradation by the ubiquitin-proteasome system is stage-dependent during muscle differentiation
    L Sun
    Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine and St Louis Children s Hospital, St Louis, MO 63110, USA
    Oncogene 26:441-8. 2007
    ..Our findings reveal an important role for both translational and post-translational regulatory mechanisms in mediating the complex program of muscle differentiation determined by the E2A proteins...
  23. pmc Molecular cloning, sequence, and tissue distribution of the human ubiquitin-activating enzyme E1
    P M Handley
    Department of Cell Biology, Washington University School of Medicine, St Louis, MO
    Proc Natl Acad Sci U S A 88:258-62. 1991
    ..Tissue distribution reveals a single 3.5-kilobase E1 message ubiquitous among tissues and cell lines...
  24. pmc c-Abl regulates p53 levels under normal and stress conditions by preventing its nuclear export and ubiquitination
    R V Sionov
    Lautenberg Center for General and Tumor Immunology, The Hebrew University Hadassah Medical School, Jerusalem 91120, Israel
    Mol Cell Biol 21:5869-78. 2001
    ..Our results help to explain how p53 is accumulated in the nucleus in response to DNA damage...
  25. pmc Complete switch from Mdm2 to human papillomavirus E6-mediated degradation of p53 in cervical cancer cells
    A Hengstermann
    Institute of Biochemistry I, Medical Faculty, University of Cologne, Joseph-Stelzmann-Strasse 52, , Germany
    Proc Natl Acad Sci U S A 98:1218-23. 2001
    ....
  26. ncbi request reprint Immunofluorescent localization of the ubiquitin-activating enzyme, E1, to the nucleus and cytoskeleton
    J S Trausch
    Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri
    Am J Physiol 264:C93-102. 1993
    ..The variable distribution of E1 among cell lines, including its apparent cytoskeletal association, suggests pleiotropic functions of this enzyme and the ubiquitin-conjugating system...
  27. ncbi request reprint 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...
  28. ncbi request reprint Identification of the ubiquitin carrier proteins, E2s, involved in signal-induced conjugation and subsequent degradation of IkappaBalpha
    H Gonen
    Department of Biochemistry and the Rappaport Family Institute for Research in the Medical Sciences, Bruce Rappaport Faculty of Medicine, Haifa 31096, Israel
    J Biol Chem 274:14823-30. 1999
    ..It is possible that different conjugating machineries operate under different physiological conditions or in different cells...
  29. ncbi request reprint Ubiquitin dependence of selective protein degradation demonstrated in the mammalian cell cycle mutant ts85
    A Ciechanover
    Cell 37:57-66. 1984
    ..We suggest that the contribution of ubiquitin-independent pathways to the degradation of short-lived proteins in this higher eucaryotic cell is no more than 10%, and possibly less...
  30. pmc A novel site for ubiquitination: the N-terminal residue, and not internal lysines of MyoD, is essential for conjugation and degradation of the protein
    K Breitschopf
    Department of Biochemistry and the Rappaport Family Institute for Research in the Medical Sciences, Technion Israel Institute of Technology, Haifa
    EMBO J 17:5964-73. 1998
    ..The polyubiquitin chain is then synthesized on an internal Lys residue of the linearly attached first ubiquitin moiety...
  31. pmc Role of UEV-1, an inactive variant of the E2 ubiquitin-conjugating enzymes, in in vitro differentiation and cell cycle behavior of HT-29-M6 intestinal mucosecretory cells
    E Sancho
    Departamento de Biologia Molecular, Instituto de Biología del Cáncer, IMIM CSIC, Barcelona, Spain
    Mol Cell Biol 18:576-89. 1998
    ..This was accompanied with a profound inhibition of the mitotic kinase, cdk1. These results suggest that UEV proteins are involved in the control of differentiation and could exert their effects by altering cell cycle distribution...
  32. ncbi request reprint The ubiquitin-activating enzyme E1 is phosphorylated and localized to the nucleus in a cell cycle-dependent manner
    A G Stephen
    Edward Mallincrodt Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 271:15608-14. 1996
    ....
  33. doi request reprint Itch: a HECT-type E3 ligase regulating immunity, skin and cancer
    G Melino
    IDI IRCCS Biochemistry Laboratory, Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Via Montpellier 1, Rome 00133, Italy
    Cell Death Differ 15:1103-12. 2008
    ..Our contribution is also an endeavor to correlate Itch substrate specificity with the pathological defects manifested by the mutant Itchy mice...