Aaron Ciechanover

Summary

Country: Israel

Publications

  1. 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
  2. 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
  3. doi request reprint ABIN-1 negatively regulates NF-kappaB by inhibiting processing of the p105 precursor
    Shai Cohen
    Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Haifa 31096, Israel
    Biochem Biophys Res Commun 389:205-10. 2009
  4. ncbi request reprint Degradation of ubiquitin: the fate of the cellular reaper
    Nitzan Shabek
    Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Haifa, Israel
    Cell Cycle 9:523-30. 2010
  5. doi request reprint Regulation of the Polycomb protein RING1B ubiquitination by USP7
    Prim de Bie
    Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Haifa 31096, Israel
    Biochem Biophys Res Commun 400:389-95. 2010
  6. pmc Intracellular Protein Degradation: From a Vague Idea through the Lysosome and the Ubiquitin-Proteasome System and onto Human Diseases and Drug Targeting
    Aaron Ciechanover
    Nobel Prize Laureate in Chemistry, 2004 Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Haifa 31096, Israel
    Rambam Maimonides Med J 3:e0001. 2012
  7. doi request reprint Intracellular protein degradation: from a vague idea through the lysosome and the ubiquitin-proteasome system and onto human diseases and drug targeting
    Aaron Ciechanover
    Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Efron Street, Bat Galim, PO Box 9649, Haifa 31096, Israel
    Bioorg Med Chem 21:3400-10. 2013
  8. doi request reprint Modification of the inflammatory mediator LRRFIP2 by the ubiquitin-like protein FAT10 inhibits its activity during cellular response to LPS
    Samuel Buchsbaum
    Center for Vascular and Tumor Biology, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Haifa 31096, Israel
    Biochem Biophys Res Commun 428:11-6. 2012
  9. doi request reprint Intracellular protein degradation: from a vague idea through the lysosome and the ubiquitin-proteasome system and onto human diseases and drug targeting
    Aaron Ciechanover
    Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Haifa, Israel
    Neurodegener Dis 10:7-22. 2012
  10. doi request reprint Intracellular protein degradation: from a vague idea thru the lysosome and the ubiquitin-proteasome system and onto human diseases and drug targeting
    Aaron Ciechanover
    Cancer and Vascular Biology Research Center, Technion Israel Institute of Technology, Haifa, Israel
    Biochim Biophys Acta 1824:3-13. 2012

Collaborators

Detail Information

Publications88

  1. 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...
  2. 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...
  3. doi request reprint ABIN-1 negatively regulates NF-kappaB by inhibiting processing of the p105 precursor
    Shai Cohen
    Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Haifa 31096, Israel
    Biochem Biophys Res Commun 389:205-10. 2009
    ..Together, the effects of ABIN-1 on p105 processing and of p105 on stabilizing ABIN-1 act to potentiate the NF-kappaB inhibitory activity of ABIN-1...
  4. ncbi request reprint Degradation of ubiquitin: the fate of the cellular reaper
    Nitzan Shabek
    Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Haifa, Israel
    Cell Cycle 9:523-30. 2010
    ..Recent findings have demonstrated that Ub can be degraded by the proteasome via three routes along with its conjugated substrate, when extended with a C-terminal tail, and as a monomer...
  5. doi request reprint Regulation of the Polycomb protein RING1B ubiquitination by USP7
    Prim de Bie
    Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Haifa 31096, Israel
    Biochem Biophys Res Commun 400:389-95. 2010
    ..Although, USP7 directly and specifically deubiquitinates RING1B in vitro and in vivo, it does not discriminate between the activating and proteolysis-targeting modes of ubiquitination, and therefore has a stabilizing effect on RING1B...
  6. pmc Intracellular Protein Degradation: From a Vague Idea through the Lysosome and the Ubiquitin-Proteasome System and onto Human Diseases and Drug Targeting
    Aaron Ciechanover
    Nobel Prize Laureate in Chemistry, 2004 Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Haifa 31096, Israel
    Rambam Maimonides Med J 3:e0001. 2012
    ....
  7. doi request reprint Intracellular protein degradation: from a vague idea through the lysosome and the ubiquitin-proteasome system and onto human diseases and drug targeting
    Aaron Ciechanover
    Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Efron Street, Bat Galim, PO Box 9649, Haifa 31096, Israel
    Bioorg Med Chem 21:3400-10. 2013
    ..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...
  8. doi request reprint Modification of the inflammatory mediator LRRFIP2 by the ubiquitin-like protein FAT10 inhibits its activity during cellular response to LPS
    Samuel Buchsbaum
    Center for Vascular and Tumor Biology, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Haifa 31096, Israel
    Biochem Biophys Res Commun 428:11-6. 2012
    ..Importantly, FATylation of LRRFIP2 interferes with its recruitment to the membrane by translocating it to the cellular insoluble fraction, thus inhibiting NF-κB activation...
  9. doi request reprint Intracellular protein degradation: from a vague idea through the lysosome and the ubiquitin-proteasome system and onto human diseases and drug targeting
    Aaron Ciechanover
    Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Haifa, Israel
    Neurodegener Dis 10:7-22. 2012
    ..Not surprisingly, aberrations in the system have been implicated in the pathogenesis of human disease, such as malignancies and neurodegenerative disorders, which subsequently led to an increasing effort to develop mechanism-based drugs...
  10. doi request reprint Intracellular protein degradation: from a vague idea thru the lysosome and the ubiquitin-proteasome system and onto human diseases and drug targeting
    Aaron Ciechanover
    Cancer and Vascular Biology Research Center, Technion Israel Institute of Technology, Haifa, Israel
    Biochim Biophys Acta 1824:3-13. 2012
    ..This article is part of a Special Issue entitled: Proteolysis 50 years after the discovery of lysosome...
  11. ncbi request reprint The ubiquitin proteolytic system: from an idea to the patient bed
    Aaron Ciechanover
    Tumor and Vascular Biology Research Center, Technion Israel Institute of Technology, Haifa, Israel
    Proc Am Thorac Soc 3:21-31. 2006
  12. ncbi request reprint The ubiquitin proteolytic system: from a vague idea, through basic mechanisms, and onto human diseases and drug targeting
    Aaron Ciechanover
    Vascular and Tumor Biology Research Center, Faculty of Medicine, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Haifa, Israel
    Neurology 66:S7-19. 2006
  13. ncbi request reprint Intracellular protein degradation: from a vague idea, through the lysosome and the ubiquitin-proteasome system, and onto human diseases and drug targeting (Nobel lecture)
    Aaron Ciechanover
    Faculty of Medicine, Technion Israel Institute of Technology, Efron Street, Bat Galim, P O Box 9649, Haifa 31096, Israel
    Angew Chem Int Ed Engl 44:5944-67. 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...
  14. 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...
  15. ncbi request reprint The ubiquitin system: pathogenesis of human diseases and drug targeting
    Aaron Ciechanover
    Tumor and Vascular Biology Research Center, The Rappaport Family Institute for Research in the Medical Sciences, and the Ruth and Bruce Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Haifa 31096, Israel
    Biochim Biophys Acta 1695:3-17. 2004
    ....
  16. ncbi request reprint Proteolysis: from the lysosome to ubiquitin and the proteasome
    Aaron Ciechanover
    Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Efron Street, Bat Galim, Haifa 31096, Israel
    Nat Rev Mol Cell Biol 6:79-87. 2005
    ..The discovery of the ubiquitin-proteasome system resolved this enigma...
  17. ncbi request reprint The ubiquitin system: from basic mechanisms to the patient bed
    Aaron Ciechanover
    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
    IUBMB Life 56:193-201. 2004
    ..Understanding of the underlying mechanisms involved is important for the development of novel, mechanism-based drugs...
  18. ncbi request reprint Ubiquitin-mediated degradation of cellular proteins in health and disease
    Aaron Ciechanover
    Department of Biochemistry, The Bruce Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel
    Hepatology 35:3-6. 2002
  19. 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
    Aaron Ciechanover
    Faculty of Medicine, Technion Israel Institute of Technology, Efron Street, Bat Galim, P O Box 9649, Haifa 31096 Israel
    Exp Biol Med (Maywood) 231:1197-211. 2006
    ..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...
  20. ncbi request reprint Intracellular protein degradation from a vague idea through the lysosome and the ubiquitin-proteasome system and on to human diseases and drug targeting: Nobel Lecture, December 8, 2004
    Aaron Ciechanover
    Vascular and Tumor Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Bat Galim, Haifa, Israel
    Ann N Y Acad Sci 1116:1-28. 2007
    ....
  21. ncbi request reprint Mechanisms of ubiquitin-mediated, limited processing of the NF-kappaB1 precursor protein p105
    A Ciechanover
    Department of Biochemistry and the Rappaport Institute for Research in the Medical Sciences, The Bruce Rappaport Faculty of Medicine, Haifa, Israel
    Biochimie 83:341-9. 2001
    ....
  22. ncbi request reprint Intracellular protein degradation: from a vague idea through the lysosome and the ubiquitin-proteasome system and onto human diseases and drug targeting
    Aaron Ciechanover
    Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Bat Galim, Haifa, Israel
    Medicina (B Aires) 70:105-19. 2010
    ..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...
  23. ncbi request reprint N-terminal ubiquitination: more protein substrates join in
    Aaron Ciechanover
    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
    Trends Cell Biol 14:103-6. 2004
    ..An important biological question relates to the evolutionary requirement for an alternative mode of ubiquitination...
  24. ncbi request reprint The ubiquitin proteasome system in neurodegenerative diseases: sometimes the chicken, sometimes the egg
    Aaron Ciechanover
    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
    Neuron 40:427-46. 2003
    ..This raises hopes for a better understanding of the pathogenetic mechanisms involved in these diseases and for the development of novel, mechanism-based therapeutic modalities...
  25. 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
    ....
  26. ncbi request reprint Mechanism of processing of the NF-kappa B2 p100 precursor: identification of the specific polyubiquitin chain-anchoring lysine residue and analysis of the role of NEDD8-modification on the SCF(beta-TrCP) ubiquitin ligase
    Ruthie E Amir
    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
    Oncogene 23:2540-7. 2004
    ..Similarly, dominant negative UBC12 inhibits, in a reversible manner, both ubiquitination and processing of p100...
  27. ncbi request reprint Degradation of the Id2 developmental regulator: targeting via N-terminal ubiquitination
    Ifat Fajerman
    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, 31096 Haifa, Israel
    Biochem Biophys Res Commun 314:505-12. 2004
    ..The mechanisms and structural motives that govern Id2 stability may have important implications to the regulation of the protein during normal differentiation and malignant transformation...
  28. doi request reprint PRAJA1 is a ubiquitin ligase for the polycomb repressive complex 2 proteins
    Muhammad Zoabi
    Center for Vascular and Tumor Biology, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Haifa 31096, Israel
    Biochem Biophys Res Commun 408:393-8. 2011
    ..Taken together, our results suggest a role for PRAJA1 in regulating the level of PRC2 by targeting its free subunits for Ub-mediated proteasomal degradation...
  29. ncbi request reprint The polycomb protein Ring1B generates self atypical mixed ubiquitin chains required for its in vitro histone H2A ligase activity
    Ronen Ben-Saadon
    Cancer and Vascular Biology Center, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Bat Galim, Haifa 31096, Israel
    Mol Cell 24:701-11. 2006
    ..The modification is required for Ring1B ability to monoubiquitinate H2A in vitro, unraveling an as yet undescribed mechanism for ligase activation via noncanonical self-ubiquitination...
  30. doi request reprint The size of the proteasomal substrate determines whether its degradation will be mediated by mono- or polyubiquitylation
    Nitzan Shabek
    Cancer and Vascular Biology Research Center, Technion Israel Institute of Technology, Haifa, Israel
    Mol Cell 48:87-97. 2012
    ..Taken together, these findings suggest that the ubiquitin proteasomal signal is adaptive, and is not always made of a long polyubiquitin chain...
  31. pmc FAT10 is a proteasomal degradation signal that is itself regulated by ubiquitination
    Samuel Buchsbaum
    Center for Vascular and Tumor Biology, Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Haifa, Israel
    Mol Biol Cell 23:225-32. 2012
    ..Degradation of FAT10 is accelerated after induction of apoptosis, suggesting that it plays a role in prosurvival pathways...
  32. 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...
  33. ncbi request reprint The NEDD8 pathway is essential for SCF(beta -TrCP)-mediated ubiquitination and processing of the NF-kappa B precursor p105
    Ruthie E Amir
    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 277:23253-9. 2002
    ....
  34. ncbi request reprint Two distinct ubiquitin-dependent mechanisms are involved in NF-kappaB p105 proteolysis
    Shai Cohen
    Center for Vascular and Tumor Biology, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Haifa 31096, Israel
    Biochem Biophys Res Commun 345:7-13. 2006
    ..Here we describe a novel region, a Processing Inhibitory Domain-PID, that upon its removal, the molecule is processed in high efficiency, which requires ubiquitination on a single, though non-specific, lysine...
  35. ncbi request reprint The tumor suppressor protein p16(INK4a) and the human papillomavirus oncoprotein-58 E7 are naturally occurring lysine-less proteins that are degraded by the ubiquitin system. Direct evidence for ubiquitination at the N-terminal residue
    Ronen Ben-Saadon
    Cancer and Vascular Biology Research Center, The Rappaport Family Institute for Research in the Medical Sciences, Technion Israel Institute of Technology, Efron Street, Bat Galim, P O Box 9649, Haifa 31096, Israel
    J Biol Chem 279:41414-21. 2004
    ..With the abundance of native lysine-less proteins, among which are important viral and cell regulators, this novel mode of protein targeting has implications for both physiological and pathophysiological processes...
  36. pmc Ubiquitin degradation with its substrate, or as a monomer in a ubiquitination-independent mode, provides clues to proteasome regulation
    Nitzan Shabek
    Cancer and Vascular Biology Research Center, Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Haifa 31096, Israel
    Proc Natl Acad Sci U S A 106:11907-12. 2009
    ....
  37. pmc Regulation of the polycomb protein Ring1B by self-ubiquitination or by E6-AP may have implications to the pathogenesis of Angelman syndrome
    Daphna Zaaroor-Regev
    Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Haifa 31096, Israel
    Proc Natl Acad Sci U S A 107:6788-93. 2010
    ....
  38. pmc Dual effects of IkappaB kinase beta-mediated phosphorylation on p105 Fate: SCF(beta-TrCP)-dependent degradation and SCF(beta-TrCP)-independent processing
    Shai Cohen
    Department of Biochemistry, Bruce Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Haifa 31096, Israel
    Mol Cell Biol 24:475-86. 2004
    ..Yet processing still requires the activity of the ubiquitin system, as it is inhibited by dominant-negative UbcH5a. We suggest that IKKbeta mediates its two distinct effects by affecting, directly and indirectly, two different E3s...
  39. ncbi request reprint Ubiquitin is degraded by the ubiquitin system as a monomer and as part of its conjugated target
    Nitzan Shabek
    Center for Vascular and Tumor Biology, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Efron Street, Bat Galim, P O Box 9649, Haifa 31096, Israel
    Biochem Biophys Res Commun 363:425-31. 2007
    ..We further show that accelerated intracellular degradation induced by stress results in depletion of ubiquitin, supporting the notion that ubiquitin is also degraded as part of the chain conjugated to its target substrate...
  40. 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
    ....
  41. 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...
  42. 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
  43. doi request reprint The complexity of recognition of ubiquitinated substrates by the 26S proteasome
    Aaron Ciechanover
    The David and Janet Polak Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Haifa 31096, Israel
    Biochim Biophys Acta 1843:86-96. 2014
    ..This article is part of a Special Issue entitled: Ubiquitin-Proteasome System. Guest Editors: Thomas Sommer and Dieter H. Wolf. ..
  44. doi request reprint The lysine48-based polyubiquitin chain proteasomal signal: not a single child anymore
    Yelena Kravtsova-Ivantsiv
    Cancer and Vascular Biology Research Center, Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel
    Angew Chem Int Ed Engl 52:192-8. 2013
    ..In addition, chains linked to residues other than internal Lys were described, all challenging the current paradigm...
  45. pmc The N-terminal domain of MyoD is necessary and sufficient for its nuclear localization-dependent degradation by the ubiquitin system
    Ronen Sadeh
    Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Haifa 31096, Israel
    Proc Natl Acad Sci U S A 105:15690-5. 2008
    ..Taken together, our data suggest that a short N-terminal segment of MyoD is necessary and sufficient to render MyoD susceptible for ubiquitin- and nuclear-dependent degradation...
  46. doi request reprint Non-canonical ubiquitin-based signals for proteasomal degradation
    Yelena Kravtsova-Ivantsiv
    Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Efron Street, Bat Galim, PO Box 9649, Haifa 31096, Israel
    J Cell Sci 125:539-48. 2012
    ..In this Commentary, we describe these recent findings and discuss the possible physiological roles of these diverse signals. Furthermore, we discuss the possible impact of this signal diversity on drug development...
  47. doi request reprint Generation of free ubiquitin chains is up-regulated in stress and facilitated by the HECT domain ubiquitin ligases UFD4 and HUL5
    Ori Braten
    Cancer and Vascular Biology Research Center, Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Efron Street, P O Box 9649, Haifa 31096, Israel
    Biochem J 444:611-7. 2012
    ..However, it appears that the stress-induced synthesis of free chains is catalyzed by a different ligase, HUL5 (HECT ubiquitin ligase 5), which is also a HECT domain E3...
  48. doi request reprint HUWE1 ubiquitinates MyoD and targets it for proteasomal degradation
    Tahel Noy
    Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Haifa 31096, Israel
    Biochem Biophys Res Commun 418:408-13. 2012
    ..Here we describe the involvement of HUWE1 in the ubiquitination and proteasomal degradation of MyoD. Furthermore, we show that the ligase can ubiquitinate the protein in its N-terminal residue...
  49. ncbi request reprint Regulation of the proapoptotic ARTS protein by ubiquitin-mediated degradation
    Rona Lotan
    Apoptosis and Cancer Research Laboratory, Pathology Department, Rambam Medical Center, Bat Galim, Haifa 31096, Israel
    J Biol Chem 280:25802-10. 2005
    ..Increased ARTS in turn leads to a decrease of Bcl-2 and Bcl-xL protein levels, cytochrome c release from mitochondria and apoptosis...
  50. ncbi request reprint Tracing the history of the ubiquitin proteolytic system: the pioneering article
    Aaron Ciechanover
    Cancer and Vascular Biology Research Center, Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Haifa, Israel
    Biochem Biophys Res Commun 387:1-10. 2009
    ....
  51. 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...
  52. doi request reprint RING1B ubiquitination and stability are regulated by ARF
    Prim de Bie
    Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Haifa 31096, Israel
    Biochem Biophys Res Commun 426:49-53. 2012
    ..By binding to the RING domain of RING1B, ARF disrupts RING1B homodimerization, providing a potential mechanism for its effect on RING1B self-ubiquitination...
  53. doi request reprint Ubiquitination and degradation of proteins
    Yelena Kravtsova-Ivantsiv
    The Rappaport Faculty of Medicine and Research Institute, Tumor and Vascular, Biology Research Center, Technion Israel Institute of Technology, 31096, Haifa, Israel
    Methods Mol Biol 753:335-57. 2011
    ..Additionally, we describe methods to follow stability (degradation) of proteins in cell-free systems and in cells...
  54. ncbi request reprint The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction
    Michael H Glickman
    Faculty of Biology and the Institute for Catalysis Science and Technology, Haifa, Israel
    Physiol Rev 82:373-428. 2002
    ..Among these are the modes of specific and timed recognition for the degradation of the many substrates and the mechanisms that underlie aberrations in the system that lead to pathogenesis of diseases...
  55. ncbi request reprint N-terminal ubiquitination
    Aaron Ciechanover
    The Center for Vascular Biology and Cancer Research, The Rappaport Faculty of Meidcine and Research Institute, Technion Israel Institute of Technology, Haifa, Israel
    Methods Mol Biol 301:255-70. 2005
    ..In this chapter we describe methods that will enable researchers to identify this novel mode of ubiquitination...
  56. 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...
  57. ncbi request reprint Inverse relationship between Skp2 ubiquitin ligase and the cyclin dependent kinase inhibitor p27Kip1 in prostate cancer
    Ofer Ben-Izhak
    Department of Pathology, Rambam Medical Center, Haifa, Israel
    J Urol 170:241-5. 2003
    ..We examined the relationship between p27 and its specific ligase Skp2 in normal and malignant prostate tissues. A possible correlation among the levels of these proteins, tumor grading and clinical state was also investigated...
  58. ncbi request reprint Modification by single ubiquitin moieties rather than polyubiquitination is sufficient for proteasomal processing of the p105 NF-kappaB precursor
    Yelena Kravtsova-Ivantsiv
    Cancer and Vascular Biology Center, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Haifa 31096, Israel
    Mol Cell 33:496-504. 2009
    ..Finally, the proteasome recognizes the multiply monoubiquitinated p105. These findings suggest that a proteolytic signal can be composed of a cluster of single ubiquitins, not necessarily a chain...
  59. 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...
  60. ncbi request reprint A novel mammalian endoplasmic reticulum ubiquitin ligase homologous to the yeast Hrd1
    Eran Nadav
    Department of Biochemistry, George S Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel
    Biochem Biophys Res Commun 303:91-7. 2003
    ..However, the homology between the human and yeast Hrd1 is limited to the N-terminal domain of the proteins, and hHrd1 does not appear to be involved in the degradation of mammalian HMGR...
  61. 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...
  62. 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...
  63. 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...
  64. ncbi request reprint Regulation of the Drosophila ubiquitin ligase DIAP1 is mediated via several distinct ubiquitin system pathways
    Y Herman-Bachinsky
    Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Haifa, Israel
    Cell Death Differ 14:861-71. 2007
    ..Our preliminary data suggest that the autoubiquitination serves to attenuate the ligase activity of DIAP1 towards its exogenous substrates...
  65. ncbi request reprint Caspase activation inhibits proteasome function during apoptosis
    Xiao Ming Sun
    MRC Toxicology Unit, Hodgkin Building, University of Leicester, PO Box 138, Lancaster Road, Leicester, LE1 9HN, United Kingdom
    Mol Cell 14:81-93. 2004
    ....
  66. ncbi request reprint Oxidative stress-related increase in ubiquitination in early coronary atherogenesis
    Joerg Hermann
    Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA
    FASEB J 17:1730-2. 2003
    ..These results demonstrate that the UPS is functionally active in early atherogenesis despite increase in oxidative stress with important repercussions in the pathophysiology and therapy of cardiovascular diseases...
  67. ncbi request reprint Early work on the ubiquitin proteasome system, an interview with Aaron Ciechanover. Interview by CDD
    Aaron Ciechanover
    Cell Death Differ 12:1167-77. 2005
  68. ncbi request reprint Ubiquitin-Proteasome-mediated degradation of Id1 is modulated by MyoD
    Julie S Trausch-Azar
    Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine and St Louis Children s Hospital, Missouri 63110, USA
    J Biol Chem 279:32614-9. 2004
    ..These results thus demonstrate that in vivo MyoD modulates the rate of Id1 degradation and suggest a dynamic interplay of these factors...
  69. ncbi request reprint Ubiquitin as a central cellular regulator
    Daniel Finley
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cell 116:S29-32, 2 p following S32. 2004
  70. ncbi request reprint E12 and E47 modulate cellular localization and proteasome-mediated degradation of MyoD and Id1
    Jody M Lingbeck
    Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St Louis, MO 63110, USA
    Oncogene 24:6376-84. 2005
    ..These results demonstrate in vivo that E12 and E47 modulate both MyoD and Id1 degradation and may have implications for the physiological regulation of muscle development...
  71. ncbi request reprint Nobel Prizes. Gold medal from cellular trash
    Gretchen Vogel
    Science 306:400-1. 2004
  72. ncbi request reprint [The 2004 Nobel Prize in Chemistry for the discovery of ubiquitin-mediated protein degradation]
    J Neefjes
    Het Nederlands Kanker Instituut Antoni van Leeuwenhoek Ziekenhuis, divisie Tumorbiologie, Plesmanlaan 121, 1066 CX Amsterdam
    Ned Tijdschr Geneeskd 148:2579-82. 2004
    This year's Nobel Prize in Chemistry has been awarded to Aaron Ciechanover, Avram Herskho and Irwin Rose for the discovery of ubiquitin-mediated protein degradation...
  73. doi request reprint The HECT family of E3 ubiquitin ligases: multiple players in cancer development
    Francesca Bernassola
    Department of Experimental Medicine and Biochemical Sciences, Biochemistry IDI IRCCS Laboratory, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy
    Cancer Cell 14:10-21. 2008
    ..Moreover, we discuss the relevance of targeting the HECT E3s, through the development of small-molecule inhibitors, as an anticancer therapeutic strategy...
  74. pmc Ubiquitin-proteasome-mediated degradation of keratin intermediate filaments in mechanically stimulated A549 cells
    Ariel Jaitovich
    Division of Pulmonary and Critical Care Medicine, Northwestern University Medical School, 240 East Huron, Chicago, IL 60611, USA
    J Biol Chem 283:25348-55. 2008
    ..These data suggest that shear stress promotes the disassembly and degradation of the keratin IF network via phosphorylation and the ubiquitin-proteasome pathway...
  75. ncbi request reprint [Nobel prize in chemistry goes to three persons with a key role in revealing the ubiquitin-mediated protein degradation pathway]
    Leena Latonen
    Biomedicum Helsinki, molekyyli ja syöpäbiologian tutkimusohjelma ja Haartman Instituuti, Helsingin yliopisto
    Duodecim 120:2868-71. 2004
  76. ncbi request reprint Nobel committee tags ubiquitin for distinction
    Alfred L Goldberg
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Neuron 45:339-44. 2005
  77. ncbi request reprint Narrative review: protein degradation and human diseases: the ubiquitin connection
    Eyal Reinstein
    Department of Internal Medicine B, Meir General Hospital and the Sackler School of Medicine, Tel Aviv University, Kfar Saba, Israel
    Ann Intern Med 145:676-84. 2006
    ..In the near future, one can expect to see the development of new, potent, and highly specific drugs that target the degradation pathways of a single or a few proteins without affecting other proteins...
  78. ncbi request reprint Ubiquitin-proteasome-mediated degradation, intracellular localization, and protein synthesis of MyoD and Id1 during muscle differentiation
    Liping Sun
    Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 280:26448-56. 2005
    ....
  79. ncbi request reprint The ubiquitin-proteasome system in cardiovascular diseases-a hypothesis extended
    Joerg Herrmann
    Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA
    Cardiovasc Res 61:11-21. 2004
    ..This review summarizes recent findings regarding the ubiquitin-proteasome system in cardiovascular diseases and discusses the potential use of proteasome inhibitors in cardiovascular therapy...
  80. pmc HdmX stimulates Hdm2-mediated ubiquitination and degradation of p53
    Laetitia K Linares
    Center for Biochemistry, Medical Faculty, and Center for Molecular Medicine, University of Cologne, Joseph Stelzmann Strasse 52, 50931 Cologne, Germany
    Proc Natl Acad Sci U S A 100:12009-14. 2003
    ....
  81. ncbi request reprint Chemistry Nobel for trio who revealed molecular death-tag
    Jim Giles
    Nature 431:729. 2004
  82. ncbi request reprint The ubiquitin-proteasome system--micro target for macro intervention?
    Joerg Herrmann
    Division of Cardiovascular Diseases Mayo Clinic, Rochester, MN 55905, USA
    Int J Cardiovasc Intervent 7:5-13. 2005
    ....
  83. ncbi request reprint Hypoxia-mediated degradation of Na,K-ATPase via mitochondrial reactive oxygen species and the ubiquitin-conjugating system
    Alejandro P Comellas
    Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
    Circ Res 98:1314-22. 2006
    ..Accordingly, we provide evidence that during hypoxia, mitochondrial reactive oxygen species are necessary to degrade the plasma membrane Na,K-ATPase via the ubiquitin-conjugating system...
  84. pmc Phosphorylation and ubiquitination are necessary for Na,K-ATPase endocytosis during hypoxia
    Laura A Dada
    Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States
    Cell Signal 19:1893-8. 2007
    ..We provide evidence that ubiquitination plays an important role in cellular adaptation to hypoxia by regulating Na,K-ATPase alpha(1)-subunit endocytosis...
  85. ncbi request reprint Regulation of Drosophila IAP1 degradation and apoptosis by reaper and ubcD1
    Hyung Don Ryoo
    Howard Hughes Medical Institute, Strang Laboratory of Cancer Research, The Rockefeller University Box 252, 1230 York Ave New York, NY 10021, USA
    Nat Cell Biol 4:432-8. 2002
    ..UBCD1 and Rpr specifically bind to DIAP1 and stimulate DIAP1 auto-ubiquitination in vitro. Our results identify a novel function of Rpr in stimulating DIAP1 auto-ubiquitination through UBCD1, thereby promoting its degradation...
  86. ncbi request reprint Increased ubiquitin immunoreactivity in unstable atherosclerotic plaques associated with acute coronary syndromes
    Joerg Herrmann
    Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota 55905, USA
    J Am Coll Cardiol 40:1919-27. 2002
    ..The current study was designed to examine whether ubiquitin expression is higher in unstable than in stable lesions of patients with acute coronary syndrome (ACS)...
  87. ncbi request reprint Determinants of nuclear and cytoplasmic ubiquitin-mediated degradation of MyoD
    Jody M Lingbeck
    Edward Mallinckrodt Department of Pediatrics and Molecular Biology and Pharmacology, Washington University School of Medicine and St Louis Children s Hospital, St Louis, Missouri 63110, USA
    J Biol Chem 278:1817-23. 2003
    ..Our results suggest that the lysine-dependent pathway is the more active pathway within the cytoplasm, whereas in the nucleus the two pathways are both active in protein degradation...