Raymond Deshaies

Summary

Affiliation: California Institute of Technology
Country: USA

Publications

  1. pmc JAMM: a metalloprotease-like zinc site in the proteasome and signalosome
    Xavier I Ambroggio
    Division of Biology, California Institute of Technology, Pasadena, California, USA
    PLoS Biol 2:E2. 2004
  2. pmc Identification of a functional docking site in the Rpn1 LRR domain for the UBA-UBL domain protein Ddi1
    Tara A Gomez
    Division of Biology, Beckman Institute, California Institute of Technology, Pasadena, CA 91125, USA
    BMC Biol 9:33. 2011
  3. pmc Components of the ubiquitin-proteasome pathway compete for surfaces on Rad23 family proteins
    Amanda M Goh
    Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA
    BMC Biochem 9:4. 2008
  4. pmc Targeted silencing of Jab1/Csn5 in human cells downregulates SCF activity through reduction of F-box protein levels
    Gregory A Cope
    Department of Biology, California Institute of Technology Pasadena, CA 91125, USA
    BMC Biochem 7:1. 2006
  5. pmc Substrate specificity analysis of protein kinase complex Dbf2-Mob1 by peptide library and proteome array screening
    Angie S Mah
    Department of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    BMC Biochem 6:22. 2005
  6. pmc The fission yeast COP9/signalosome is involved in cullin modification by ubiquitin-related Ned8p
    C Zhou
    Department of Cancer Cell Biology, Harvard School of Public Health, Boston, MA, USA
    BMC Biochem 2:7. 2001
  7. doi request reprint RING domain E3 ubiquitin ligases
    Raymond J Deshaies
    Howard Hughes Medical Institute and Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    Annu Rev Biochem 78:399-434. 2009
  8. doi request reprint Control of cullin-ring ubiquitin ligase activity by nedd8
    Raymond J Deshaies
    Division of Biology, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California, USA
    Subcell Biochem 54:41-56. 2010
  9. ncbi request reprint Phosphorylation by cyclin B-Cdk underlies release of mitotic exit activator Cdc14 from the nucleolus
    Ramzi Azzam
    Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    Science 305:516-9. 2004
  10. ncbi request reprint Role of predicted metalloprotease motif of Jab1/Csn5 in cleavage of Nedd8 from Cul1
    Gregory A Cope
    Department of Biology, California Institute of Technology Caltech, Pasadena, CA 91125, USA
    Science 298:608-11. 2002

Research Grants

  1. Regulation of cullin-RING ligases by Nedd8
    Raymond Deshaies; Fiscal Year: 2007
  2. Regulation of cullin-RING ligases by Nedd8
    Raymond J Deshaies; Fiscal Year: 2010
  3. Regulation of cullin-RING ligases by Nedd8
    Raymond J Deshaies; Fiscal Year: 2010
  4. Regulation of cullin-RING ligases by Nedd8
    Raymond Deshaies; Fiscal Year: 2009
  5. Functions and Substrates of COP9 Signalosome
    Raymond Deshaies; Fiscal Year: 2005
  6. A SIGNALING NETWORK THAT GOVERNS M PHASE EXIT
    Raymond Deshaies; Fiscal Year: 2002
  7. Mechanism of mitotic exit in budding yeast
    Raymond Deshaies; Fiscal Year: 2009

Collaborators

Detail Information

Publications45

  1. pmc JAMM: a metalloprotease-like zinc site in the proteasome and signalosome
    Xavier I Ambroggio
    Division of Biology, California Institute of Technology, Pasadena, California, USA
    PLoS Biol 2:E2. 2004
    ..The active site-like architecture specified by the JAMM motif motivates structure-based approaches to the study of JAMM domain proteins and the development of therapeutic proteasome and signalosome inhibitors...
  2. pmc Identification of a functional docking site in the Rpn1 LRR domain for the UBA-UBL domain protein Ddi1
    Tara A Gomez
    Division of Biology, Beckman Institute, California Institute of Technology, Pasadena, CA 91125, USA
    BMC Biol 9:33. 2011
    ..It has been proposed that shuttling receptors dock on the proteasome via Rpn1, but the precise nature of the docking site remains poorly defined...
  3. pmc Components of the ubiquitin-proteasome pathway compete for surfaces on Rad23 family proteins
    Amanda M Goh
    Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA
    BMC Biochem 9:4. 2008
    ....
  4. pmc Targeted silencing of Jab1/Csn5 in human cells downregulates SCF activity through reduction of F-box protein levels
    Gregory A Cope
    Department of Biology, California Institute of Technology Pasadena, CA 91125, USA
    BMC Biochem 7:1. 2006
    ..The removal of Nedd8 is catalyzed by the Jab1/MPN domain metalloenzyme (JAMM) motif within the Csn5 subunit of the Cop9 Signalosome...
  5. pmc Substrate specificity analysis of protein kinase complex Dbf2-Mob1 by peptide library and proteome array screening
    Angie S Mah
    Department of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    BMC Biochem 6:22. 2005
    ..The components of MEN that act upstream of Dbf2-Mob1 have been characterized, but physiological substrates for Dbf2-Mob1 have yet to be identified...
  6. pmc The fission yeast COP9/signalosome is involved in cullin modification by ubiquitin-related Ned8p
    C Zhou
    Department of Cancer Cell Biology, Harvard School of Public Health, Boston, MA, USA
    BMC Biochem 2:7. 2001
    ..pombe CSN, results in accumulation of Pcu1p exclusively in the modified form. However, it remained unclear whether this reflects global control of all cullins by the entire CSN complex...
  7. doi request reprint RING domain E3 ubiquitin ligases
    Raymond J Deshaies
    Howard Hughes Medical Institute and Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    Annu Rev Biochem 78:399-434. 2009
    ..Despite their critical importance, our knowledge of the physiological partners, biological functions, substrates, and mechanism of action for most RING E3s remains at a rudimentary stage...
  8. doi request reprint Control of cullin-ring ubiquitin ligase activity by nedd8
    Raymond J Deshaies
    Division of Biology, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California, USA
    Subcell Biochem 54:41-56. 2010
    ..Here, we review how the Nedd8 cycle controls CRL activity and how perturbations of this cycle can lead to disease...
  9. ncbi request reprint Phosphorylation by cyclin B-Cdk underlies release of mitotic exit activator Cdc14 from the nucleolus
    Ramzi Azzam
    Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    Science 305:516-9. 2004
    ..Thus, a regulatory circuit exists to ensure that the arbiter of the mitotic state, Cdk, sets in motion events that culminate in exit from mitosis...
  10. ncbi request reprint Role of predicted metalloprotease motif of Jab1/Csn5 in cleavage of Nedd8 from Cul1
    Gregory A Cope
    Department of Biology, California Institute of Technology Caltech, Pasadena, CA 91125, USA
    Science 298:608-11. 2002
    ..We propose that JAMM isopeptidases play important roles in a variety of physiological pathways...
  11. ncbi request reprint In vitro reconstitution of SCF substrate ubiquitination with purified proteins
    Matthew D Petroski
    Howard Hughes Medical Institute, Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    Methods Enzymol 398:143-58. 2005
    ..Based on our experience in reconstituting Sic1 ubiquitination, we suggest some parameters to consider that should be generally applicable to the study of different SCF complexes and other ubiquitin ligases...
  12. ncbi request reprint A putative stimulatory role for activator turnover in gene expression
    J Russell Lipford
    Howard Hughes Medical Institute, Division of Biology, MC 156 29, California Institute of Technology, 1200 E California Boulevard, Pasadena, California 91125, USA
    Nature 438:113-6. 2005
    ..Expression of a stable phospho-site mutant of Gcn4 (ref. 7) or disruption of the kinases that target Gcn4 for turnover alleviated the sensitivity of Gcn4 activity to defects in the UPS...
  13. ncbi request reprint Ubistatins inhibit proteasome-dependent degradation by binding the ubiquitin chain
    Rati Verma
    Department of Biology, Howard Hughes Medical Institute HHMI, California Institute of Technology, Pasadena, CA 91125, USA
    Science 306:117-20. 2004
    ..The same interface is recognized by ubiquitin-chain receptors of the proteasome, indicating that ubistatins act by disrupting a critical protein-protein interaction in the ubiquitin-proteasome system...
  14. ncbi request reprint Role of Rpn11 metalloprotease in deubiquitination and degradation by the 26S proteasome
    Rati Verma
    Department of Biology and Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA
    Science 298:611-5. 2002
    ..Our findings reveal an unexpected coupling between substrate deubiquitination and degradation and suggest a unifying rationale for the presence of the lid in eukaryotic proteasomes...
  15. ncbi request reprint COP9 signalosome: a multifunctional regulator of SCF and other cullin-based ubiquitin ligases
    Gregory A Cope
    Division of Biology, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA
    Cell 114:663-71. 2003
    ..Here, we summarize what is known about CSN, and discuss hypotheses for how CSN promotes the activity of SCF ubiquitin ligases...
  16. ncbi request reprint Multiubiquitin chain receptors define a layer of substrate selectivity in the ubiquitin-proteasome system
    Rati Verma
    Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA
    Cell 118:99-110. 2004
    ..We propose that recruitment of substrates to the proteasome by MCBPs provides an additional layer of substrate selectivity in the UPS...
  17. ncbi request reprint Function and regulation of cullin-RING ubiquitin ligases
    Matthew D Petroski
    Division of Biology and Howard Hughes Medical Institute, California Institute of Technology, 1200 East California Boulevard, Pasadena, California 91125, USA
    Nat Rev Mol Cell Biol 6:9-20. 2005
    ..In this review, we focus on the composition, regulation and function of cullin-RING ligases, and describe how these enzymes can be characterized by a set of general principles...
  18. ncbi request reprint Redundant degrons ensure the rapid destruction of Sic1 at the G1/S transition of the budding yeast cell cycle
    Matthew D Petroski
    Howard Hughes Medical Institute and Division of Biology, California Institute of Technology, Pasadena, California 91125, USA
    Cell Cycle 2:410-1. 2003
  19. ncbi request reprint Quantitative profiling of ubiquitylated proteins reveals proteasome substrates and the substrate repertoire influenced by the Rpn10 receptor pathway
    Thibault Mayor
    Howard Hughes Medical Institute, Division of Biology, California Institute of Technology, Pasadena, California 91125, USA
    Mol Cell Proteomics 6:1885-95. 2007
    ..This approach illustrates the feasibility of systems-level quantitative analysis to map enzyme-substrate networks in the UPS...
  20. ncbi request reprint Charting the protein complexome in yeast by mass spectrometry
    Raymond J Deshaies
    Divison of Biology, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California 91125, USA
    Mol Cell Proteomics 1:3-10. 2002
    ..In this article we review some of our recent efforts, and describe a promising new approach for using mass spectrometry to dissect protein interaction networks...
  21. pmc Dbf2-Mob1 drives relocalization of protein phosphatase Cdc14 to the cytoplasm during exit from mitosis
    Dane A Mohl
    Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    J Cell Biol 184:527-39. 2009
    ..Our results define a mechanism by which the MEN promotes exit from mitosis...
  22. pmc A conditional yeast E1 mutant blocks the ubiquitin-proteasome pathway and reveals a role for ubiquitin conjugates in targeting Rad23 to the proteasome
    Nazli Ghaboosi
    Howard Hughes Medical Institute, Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    Mol Biol Cell 18:1953-63. 2007
    ..We propose that recognition of polyubiquitin chains by Rad23 promotes its shuttling to the proteasome in vivo...
  23. ncbi request reprint Diverse roles for ubiquitin-dependent proteolysis in transcriptional activation
    J Russell Lipford
    Division of Biology, California Institute of Biology, 1200 East California Boulevard, Pasadena, CA 91125, USA
    Nat Cell Biol 5:845-50. 2003
    ..UPS might promote transcription by several mechanisms, and in some cases, even the final step of the UPS - proteolysis - might enhance activator function...
  24. pmc Multiple telophase arrest bypassed (tab) mutants alleviate the essential requirement for Cdc15 in exit from mitosis in S. cerevisiae
    Wenying Shou
    Division of Biology, 156 29 Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA
    BMC Genet 3:4. 2002
    ..However, the remaining tab mutants were not characterized...
  25. pmc Cdc48/p97 mediates UV-dependent turnover of RNA Pol II
    Rati Verma
    California Institute of Technology, Pasadena, CA 91125, USA
    Mol Cell 41:82-92. 2011
    ..These data reveal an intimate coupling of function between proteasomes and Cdc48 that we suggest is necessary to sustain processive degradation of unstable subunits of some macromolecular protein complexes...
  26. pmc The acidic tail of the Cdc34 ubiquitin-conjugating enzyme functions in both binding to and catalysis with ubiquitin ligase SCFCdc4
    Gary Kleiger
    Howard Hughes Medical Institute and the Division of Biology, California Institute of Technology, Pasadena, California 91125, USA
    J Biol Chem 284:36012-23. 2009
    ..Finally, a search of the yeast proteome uncovered scores of proteins containing highly acidic stretches of amino acids, hinting that electrostatic interactions may be a common mechanism for facilitating protein assembly...
  27. pmc UBXD7 binds multiple ubiquitin ligases and implicates p97 in HIF1alpha turnover
    Gabriela Alexandru
    Division of Biology, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA
    Cell 134:804-16. 2008
    ..The large number of ubiquitin ligases found associated with UBX proteins suggests that p97 plays a far broader role than previously anticipated in the global regulation of protein turnover...
  28. ncbi request reprint Applicability of tandem affinity purification MudPIT to pathway proteomics in yeast
    Johannes Graumann
    Department of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    Mol Cell Proteomics 3:226-37. 2004
    ..e. "pathway proteomics") by systematic application of TAP-MudPIT...
  29. ncbi request reprint Context of multiubiquitin chain attachment influences the rate of Sic1 degradation
    Matthew D Petroski
    Howard Hughes Medical Institute, Division of Biology 156 29, California Institute of Technology, 1200 E California Boulevard, Pasadena, CA 91125, USA
    Mol Cell 11:1435-44. 2003
    ..Our results reveal that a single multiubiquitin chain can sustain a physiological turnover rate, but that chain position plays an unexpectedly significant role in the rate of proteasomal proteolysis...
  30. ncbi request reprint Analysis of polyubiquitin conjugates reveals that the Rpn10 substrate receptor contributes to the turnover of multiple proteasome targets
    Thibault Mayor
    Howard Hughes Medical Institute, Division of Biology, MC 156 29, California Institute of Technology, Pasadena, California 91125, USA
    Mol Cell Proteomics 4:741-51. 2005
    ....
  31. pmc Chemical genetics screen for enhancers of rapamycin identifies a specific inhibitor of an SCF family E3 ubiquitin ligase
    Mariam Aghajan
    Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, and the Molecular Biology Institute, University of California, Los Angeles, California, USA
    Nat Biotechnol 28:738-42. 2010
    ..Our results show that there is no fundamental barrier to obtaining specific inhibitors to modulate function of individual SCF complexes...
  32. ncbi request reprint Mechanism of lysine 48-linked ubiquitin-chain synthesis by the cullin-RING ubiquitin-ligase complex SCF-Cdc34
    Matthew D Petroski
    Howard Hughes Medical Institute, Division of Biology, 156 29, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA
    Cell 123:1107-20. 2005
    ..We propose that the acidic loop favorably positions K48 of a substrate-linked ubiquitin to attack SCF bound Cdc34 approximately ubiquitin thioester and thereby enables processive synthesis of K48-linked ubiquitin chains by SCF-Cdc34...
  33. pmc Rapid E2-E3 assembly and disassembly enable processive ubiquitylation of cullin-RING ubiquitin ligase substrates
    Gary Kleiger
    Howard Hughes Medical Institute and the Division of Biology, 156 29, California Institute of Technology, Pasadena, CA 91125, USA
    Cell 139:957-68. 2009
    ..We discuss different strategies by which processive ubiquitin chain synthesis may be achieved...
  34. pmc Transcription factor Nrf1 mediates the proteasome recovery pathway after proteasome inhibition in mammalian cells
    Senthil K Radhakrishnan
    Division of Biology, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA
    Mol Cell 38:17-28. 2010
    ..Taken together, our results suggest that Nrf1-mediated proteasome homeostasis could be an attractive target for therapeutic intervention in cancer...
  35. pmc Multimodal activation of the ubiquitin ligase SCF by Nedd8 conjugation
    Anjanabha Saha
    Howard Hughes Medical Institute, Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    Mol Cell 32:21-31. 2008
    ....
  36. ncbi request reprint Two-step affinity purification of multiubiquitylated proteins from Saccharomyces cerevisiae
    Thibault Mayor
    Division of Biology, California Institute of Technology, Pasadena, California, USA
    Methods Enzymol 399:385-92. 2005
    ....
  37. ncbi request reprint Evaluation of a diffusion-driven mechanism for substrate ubiquitination by the SCF-Cdc34 ubiquitin ligase complex
    Matthew D Petroski
    Howard Hughes Medical Institute, Division of Biology, 156 29, California Institute of Technology, 1200 East California Boulevard, Pasadena, California 91125, USA
    Mol Cell 24:523-34. 2006
    ..We propose that interactions between Cdc34 approximately Ub and SCF directly activate ubiquitin transfer within a substrate-SCF-Cdc34 approximately Ub ternary complex...
  38. pmc Detection of sequential polyubiquitylation on a millisecond timescale
    Nathan W Pierce
    Howard Hughes Medical Institute, Division of Biology, MC 156 29, Pasadena, California 91125, USA
    Nature 462:615-9. 2009
    ..Our results present an unprecedented glimpse into the mechanism of RING ubiquitin ligases and illuminate the quantitative parameters that underlie the rate and pattern of ubiquitin chain assembly...
  39. ncbi request reprint Mass spectrometry-based methods for phosphorylation site mapping of hyperphosphorylated proteins applied to Net1, a regulator of exit from mitosis in yeast
    Susan Loughrey Chen
    Proteomics and Biological Mass Spectrometry, GlaxoSmithKline, King of Prussia, Pennsylvania 19406, USA
    Mol Cell Proteomics 1:186-96. 2002
    ..The failure of any single method to identify all sites in highly phosphorylated Net1N, however, raises significant concerns about how feasible it is to map phosphorylation sites throughout the proteome using existing technologies...
  40. pmc Mutations in the hydrophobic core of ubiquitin differentially affect its recognition by receptor proteins
    Aydin Haririnia
    Department of Chemistry and Biochemistry, Center for Biomolecular Structure and Organization, University of Maryland, College Park, MD 20742, USA
    J Mol Biol 375:979-96. 2008
    ..These studies emphasize an unexpected role for Ub's core in molecular recognition and suggest that the diversity of protein-protein interactions in which Ub engages placed enormous constraints on its evolvability...
  41. pmc Loss of CDC5 function in Saccharomyces cerevisiae leads to defects in Swe1p regulation and Bfa1p/Bub2p-independent cytokinesis
    Chong Jin Park
    Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Genetics 163:21-33. 2003
    ..Thus, Cdc5p contributes to the activation of the Swe1p-dependent Cdc28p/Clb pathway, normal septin function, and cytokinesis...
  42. pmc Structural organization of the 19S proteasome lid: insights from MS of intact complexes
    Michal Sharon
    Department of Chemistry, University of Cambridge, Cambridge, United Kingdom
    PLoS Biol 4:e267. 2006
    ..More generally, the results highlight the potential of mass spectrometry to add crucial insight into the structural organization of an endogenous, wild-type complex...
  43. ncbi request reprint Human De-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin ligase
    Ingrid E Wertz
    Department of Molecular Oncology, Genentech, Inc, South San Francisco, CA 94080, USA
    Science 303:1371-4. 2004
    ..Ablation of any subunit by RNA interference stabilized c-Jun and increased c-Jun-activated transcription. These findings characterize a c-Jun ubiquitin ligase and define a specific function for hDET1 in mammalian cells...
  44. ncbi request reprint Development of Protacs to target cancer-promoting proteins for ubiquitination and degradation
    Kathleen M Sakamoto
    Division of Hematology Oncology, Mattel Children s Hospital at the University of California Los Angeles, 90095 1752, USA
    Mol Cell Proteomics 2:1350-8. 2003
    ..Future improvements to this technology may yield a general approach to treat a number of human diseases, including cancer...
  45. ncbi request reprint Mapping phosphorylation sites in proteins by mass spectrometry
    Wenying Shou
    Rockefeller University, New York, New York 10021, USA
    Methods Enzymol 351:279-96. 2002

Research Grants20

  1. Regulation of cullin-RING ligases by Nedd8
    Raymond Deshaies; Fiscal Year: 2007
    ....
  2. Regulation of cullin-RING ligases by Nedd8
    Raymond J Deshaies; Fiscal Year: 2010
    ..Besides being an important research tool, a Csn5 inhibitor has great potential to serve as a starting point for development of new therapeutic drugs to modulate CRL activity for clinical benefit. ..
  3. Regulation of cullin-RING ligases by Nedd8
    Raymond J Deshaies; Fiscal Year: 2010
    ....
  4. Regulation of cullin-RING ligases by Nedd8
    Raymond Deshaies; Fiscal Year: 2009
    ....
  5. Functions and Substrates of COP9 Signalosome
    Raymond Deshaies; Fiscal Year: 2005
    ..abstract_text> ..
  6. A SIGNALING NETWORK THAT GOVERNS M PHASE EXIT
    Raymond Deshaies; Fiscal Year: 2002
    ..It is hoped that molecular insights into the mechanisms of mitotic exit that emerge from the studies proposed here will provide a rich new source of potential targets for anti-cancer chemotherapy. ..
  7. Mechanism of mitotic exit in budding yeast
    Raymond Deshaies; Fiscal Year: 2009
    ..Our work may also provide a useful paradigm for understanding how other pathways that employ reversible nucleolar sequestra - such as the ARF-Mdm2- p53 circuit - are regulated. ..