Guy Salvesen

Summary

Affiliation: The Burnham Institute
Country: USA

Publications

  1. ncbi request reprint Caspase 8: igniting the death machine
    G S Salvesen
    Programs in Cell Death and Aging Research The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, California, 92037, USA
    Structure 7:R225-9. 1999
  2. ncbi request reprint Caspase mechanisms
    Guy S Salvesen
    Program on Apoptosis and Cell Death, Burnham Institute for Medical Research, 10901 N Torrey Pines Road, La Jolla, CA 92037, USA
    Adv Exp Med Biol 615:13-23. 2008
  3. ncbi request reprint Caspases and apoptosis
    Guy S Salvesen
    Program in Apoptosis and Cell Death Research, Burnham Institute, La Jolla, CA 92037, USA
    Essays Biochem 38:9-19. 2002
  4. ncbi request reprint Caspase activation - stepping on the gas or releasing the brakes? Lessons from humans and flies
    Guy S Salvesen
    Program in Apoptosis and Cell Death Research, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92122, USA
    Oncogene 23:2774-84. 2004
  5. ncbi request reprint Role of proteolysis in caspase-8 activation and stabilization
    Cristina Pop
    Program in Apoptosis and Cell Death Research, The Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
    Biochemistry 46:4398-407. 2007
  6. ncbi request reprint Human caspase-7 activity and regulation by its N-terminal peptide
    Jean Bernard Denault
    Program in Apoptosis and Cell Death Research, The Burnham Institute, La Jolla, California 92122, USA
    J Biol Chem 278:34042-50. 2003
  7. ncbi request reprint The apoptosome activates caspase-9 by dimerization
    Cristina Pop
    Program in Apoptosis and Cell Death Research, The Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
    Mol Cell 22:269-75. 2006
  8. ncbi request reprint Engineered hybrid dimers: tracking the activation pathway of caspase-7
    Jean Bernard Denault
    The Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
    Mol Cell 23:523-33. 2006
  9. pmc Positional-scanning fluorigenic substrate libraries reveal unexpected specificity determinants of DUBs (deubiquitinating enzymes)
    Marcin Drag
    Apoptosis and Cell Death Research, Burnham Institute for Medical Research, La Jolla, CA 92037, USA
    Biochem J 415:367-75. 2008
  10. ncbi request reprint Activation and substrate specificity of caspase-14
    Jowita Mikolajczyk
    The Program in Apoptosis and Cell Death Research, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
    Biochemistry 43:10560-9. 2004

Research Grants

  1. INHIBITION OF PROTEASES BY IAPS
    Guy Salvesen; Fiscal Year: 2001
  2. Apoptosis: Basic Mechanisms and Disease Relevance
    Guy Salvesen; Fiscal Year: 2003
  3. PROTEASES IN NEURONAL CELL DEATH
    Guy Salvesen; Fiscal Year: 2003
  4. PROTEINASE INHIBITORY MECHANISMS OF SERPINS
    Guy Salvesen; Fiscal Year: 2003
  5. PROTEASES IN NEURONAL CELL DEATH
    Guy Salvesen; Fiscal Year: 2004
  6. ASPIC, a novel MS technology, applied to degradomics
    Guy Salvesen; Fiscal Year: 2004
  7. PROTEASES IN NEURONAL CELL DEATH
    Guy Salvesen; Fiscal Year: 2005
  8. ASPIC, a novel MS technology, applied to degradomics
    Guy Salvesen; Fiscal Year: 2005
  9. PROTEASES IN NEURONAL CELL DEATH
    Guy Salvesen; Fiscal Year: 2006
  10. PROTEASES IN NEURONAL CELL DEATH
    Guy Salvesen; Fiscal Year: 2007

Collaborators

Detail Information

Publications79

  1. ncbi request reprint Caspase 8: igniting the death machine
    G S Salvesen
    Programs in Cell Death and Aging Research The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, California, 92037, USA
    Structure 7:R225-9. 1999
    ..Two papers in the September issue of Structure with Folding & Design have for the first time revealed the structure of the key apoptotic initiator, caspase 8...
  2. ncbi request reprint Caspase mechanisms
    Guy S Salvesen
    Program on Apoptosis and Cell Death, Burnham Institute for Medical Research, 10901 N Torrey Pines Road, La Jolla, CA 92037, USA
    Adv Exp Med Biol 615:13-23. 2008
    ....
  3. ncbi request reprint Caspases and apoptosis
    Guy S Salvesen
    Program in Apoptosis and Cell Death Research, Burnham Institute, La Jolla, CA 92037, USA
    Essays Biochem 38:9-19. 2002
    ..In vertebrates, a subset of caspases has evolved to participate in the activation of pro-inflammatory cytokines, and thus members of the caspase family participate in one of two very distinct intracellular signalling pathways...
  4. ncbi request reprint Caspase activation - stepping on the gas or releasing the brakes? Lessons from humans and flies
    Guy S Salvesen
    Program in Apoptosis and Cell Death Research, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92122, USA
    Oncogene 23:2774-84. 2004
    ..This sets the scene for therapy to reinstate the normal death mechanisms that have been overcome in a cancer cell's quest for immortality...
  5. ncbi request reprint Role of proteolysis in caspase-8 activation and stabilization
    Cristina Pop
    Program in Apoptosis and Cell Death Research, The Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
    Biochemistry 46:4398-407. 2007
    ..Autoproteolysis of caspase-8 may be a mechanism for increasing the lifetime of the dimeric enzyme following dissociation from its activating complex at the cell membrane...
  6. ncbi request reprint Human caspase-7 activity and regulation by its N-terminal peptide
    Jean Bernard Denault
    Program in Apoptosis and Cell Death Research, The Burnham Institute, La Jolla, California 92122, USA
    J Biol Chem 278:34042-50. 2003
    ..The N-peptide must first be removed, probably by caspase-3, before efficient conversion and activation of the zymogen can occur in vivo...
  7. ncbi request reprint The apoptosome activates caspase-9 by dimerization
    Cristina Pop
    Program in Apoptosis and Cell Death Research, The Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
    Mol Cell 22:269-75. 2006
    ....
  8. ncbi request reprint Engineered hybrid dimers: tracking the activation pathway of caspase-7
    Jean Bernard Denault
    The Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
    Mol Cell 23:523-33. 2006
    ..However, we see no evidence for an analogous intermediate of the related executioner caspase-3. Our study demonstrates the efficiency by which the executioner caspases are activated in vivo...
  9. pmc Positional-scanning fluorigenic substrate libraries reveal unexpected specificity determinants of DUBs (deubiquitinating enzymes)
    Marcin Drag
    Apoptosis and Cell Death Research, Burnham Institute for Medical Research, La Jolla, CA 92037, USA
    Biochem J 415:367-75. 2008
    ..Together, our results reveal the importance of the dual features of (1) substrate specificity and (2) the mechanism of ubiquitin binding in determining deubiquitination by this group of proteases...
  10. ncbi request reprint Activation and substrate specificity of caspase-14
    Jowita Mikolajczyk
    The Program in Apoptosis and Cell Death Research, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
    Biochemistry 43:10560-9. 2004
    ..The results obtained with human caspase-14 classify this enzyme as a cytokine activator, but the mouse enzyme shows preferences similar to apical apoptotic caspases...
  11. pmc XIAP inhibits caspase-3 and -7 using two binding sites: evolutionarily conserved mechanism of IAPs
    Fiona L Scott
    Program in Apoptosis and Cell Death Research, The Burnham Institute, La Jolla, CA 92037, USA
    EMBO J 24:645-55. 2005
    ..Since apical caspases utilize this cleavage site differently, we predict that the origin of the death stimulus should dictate the efficiency of inhibition by XIAP...
  12. ncbi request reprint The human anti-apoptotic proteins cIAP1 and cIAP2 bind but do not inhibit caspases
    Brendan P Eckelman
    Program in Cell Death and Apoptosis Research, Burnham Institute for Medical Research and the Graduate Program in Molecular Pathology, University of California San Diego, La Jolla, California 92037, USA
    J Biol Chem 281:3254-60. 2006
    ..Consequently, although the binding function of the cIAP BIRs may be important for their physiologic function, caspase inhibition is not...
  13. ncbi request reprint A unified model for apical caspase activation
    Kelly M Boatright
    The Program in Apoptosis and Cell Death Research, Burnham Institute, 10901 North Torrey Pines Road, University of California, San Diego, La Jolla, CA 92037, USA
    Mol Cell 11:529-41. 2003
    ..We propose a unified caspase activation hypothesis whereby apical caspases are activated by dimerization of monomeric zymogens...
  14. pmc Dominant-interfering forms of MEF2 generated by caspase cleavage contribute to NMDA-induced neuronal apoptosis
    Shu ichi Okamoto
    Center for Neuroscience and Aging, Apoptosis and Cell Death Research Program, The Burnham Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 99:3974-9. 2002
    ..Additionally, we show that similar MEF2 cleavage fragments are generated in vivo during focal stroke damage. Hence, this pathway appears to have pathophysiological relevance in vivo...
  15. ncbi request reprint Small-molecule antagonists of apoptosis suppressor XIAP exhibit broad antitumor activity
    Aaron D Schimmer
    The Burnham Institute, La Jolla, CA 92037, USA
    Cancer Cell 5:25-35. 2004
    ..Active compounds also suppressed growth of established tumors in xenograft models in mice, while displaying little toxicity to normal tissues. These findings validate IAPs as targets for cancer drug discovery...
  16. pmc Nicotinamide rescues human embryonic stem cell-derived neuroectoderm from parthanatic cell death
    Flavio Cimadamore
    Burnham Institute for Medical Research, La Jolla, California 92037, USA
    Stem Cells 27:1772-81. 2009
    ..We argue that small natural metabolites provide a powerful physiological tool to optimize hESC differentiation compatible with the requirements of regenerative medicine...
  17. pmc Aminopeptidase fingerprints, an integrated approach for identification of good substrates and optimal inhibitors
    Marcin Drag
    Apoptosis and Cell Death Research Program, The Burnham Institute for Medical Research, La Jolla, California 92037, USA
    J Biol Chem 285:3310-8. 2010
    ....
  18. ncbi request reprint Mechanisms of caspase activation
    Kelly M Boatright
    Program in Cell Death and Apoptosis Research, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Curr Opin Cell Biol 15:725-31. 2003
    ..This mechanism is proximity-induced dimerization without cleavage, and its elucidation has led to the revision of concepts of feedback regulation of apoptosis...
  19. ncbi request reprint Small ubiquitin-related modifier (SUMO)-specific proteases: profiling the specificities and activities of human SENPs
    Jowita Mikolajczyk
    Program in Apoptosis and Cell Death Research, Burnham Institute for Medical Research, La Jolla, California 92037, USA
    J Biol Chem 282:26217-24. 2007
    ..Using these synthetic substrates we reveal that the SUMO domain enhances catalysis of SENP1, -2, -5, -6, and -7, demonstrating substrate-induced activation of SENPs by SUMOs...
  20. ncbi request reprint Activity profiling of human deSUMOylating enzymes (SENPs) with synthetic substrates suggests an unexpected specificity of two newly characterized members of the family
    Marcin Drag
    Apoptosis and Cell Death Research Program, Burnham Institute for Medical Research, La Jolla, CA 92037, USA
    Biochem J 409:461-9. 2008
    ..We also show that SENP6 and 7 have an unexpected specificity that distinguishes them from other members of the family, implying that, in contrast to previous predictions, their natural substrate(s) may not be SUMO conjugates...
  21. pmc The BIR domain of IAP-like protein 2 is conformationally unstable: implications for caspase inhibition
    Hwain Shin
    Program in Apoptosis and Cell Death Research, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Biochem J 385:1-10. 2005
    ..We speculate that ILP2 requires assistance from unidentified cellular factors to be an effective inhibitor of apoptosis in vivo...
  22. pmc Inhibitor specificity of recombinant and endogenous caspase-9
    Ciara A Ryan
    Program for Apoptosis and Cell Death Research, The Burnham Institute, 10901 North, Torrey Pines Road, La Jolla, CA 92037, USA
    Biochem J 366:595-601. 2002
    ..These results consolidate previous findings that CrmA is a potent inhibitor of caspase-9 in vitro, yet fails to block caspase-9-mediated cell death...
  23. ncbi request reprint DeSUMOylating enzymes--SENPs
    Marcin Drag
    Program in Apoptosis and Cell Death Research, Burnham Institute for Medical Research, La Jolla, CA 92037, USA
    IUBMB Life 60:734-42. 2008
    ..We discuss recent progress on the human SENPs and their substrates...
  24. pmc Caspase-8 cleaves histone deacetylase 7 and abolishes its transcription repressor function
    Fiona L Scott
    Program in Apoptosis and Cell Death Research, Burnham Institute for Medical Research, La Jolla, California 92037, USA
    J Biol Chem 283:19499-510. 2008
    ..Importantly, cleavage of HDAC7 alters its subcellular localization and abrogates its Nur77 repressor function. Thus we demonstrate a direct role for initiator caspase-mediated proteolysis in promoting gene transcription...
  25. ncbi request reprint The apoptosome: signalling platform of cell death
    Stefan J Riedl
    Program in Apoptosis and Cell Death Research, The Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Nat Rev Mol Cell Biol 8:405-13. 2007
    ..The formation of the apoptosome and the activation of its effector, caspase-9, reveals a sophisticated mechanism that might be more common than was initially thought...
  26. ncbi request reprint The nematode death machine in 3D
    Cristina Pop
    Program in Apoptosis and Cell Death Research, The Burnham Institute for Medical Research, La Jolla, California 92037, USA
    Cell 123:192-3. 2005
    ..Intriguingly, CED-4 comprises a AAA+ type ATPase domain yet does not seem to need ATP hydrolysis for activity...
  27. pmc Activation and specificity of human caspase-10
    Katherine Wachmann
    Program in Apoptosis and Cell Death Research, Sanford BurnhamMedical Research Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
    Biochemistry 49:8307-15. 2010
    ....
  28. pmc Transnitrosylation of XIAP regulates caspase-dependent neuronal cell death
    Tomohiro Nakamura
    Del E Webb Center for Neuroscience, Aging, and Stem Cell Research, Sanford Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Mol Cell 39:184-95. 2010
    ..These findings provide insights into the regulation of caspase activation in neurodegenerative disorders mediated, at least in part, by nitrosative stress...
  29. doi request reprint Transferring death: a role for tRNA in apoptosis regulation
    Bram J van Raam
    Program in Apoptosis and Cell Death Research, Sanford Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Mol Cell 37:591-2. 2010
    ..In this issue of Molecular Cell, Mei et al. show that cytochrome c is itself regulated by binding to tRNA, providing an unanticipated level of control of cell fate decisions...
  30. pmc Activation of caspases-8 and -10 by FLIP(L)
    Kelly M Boatright
    Program in Apoptosis and Cell Death Research, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Biochem J 382:651-7. 2004
    ..Significantly, the barrier for heterodimer formation is lower than that for homodimer formation, suggesting that FLIP(L) is a more potent activator of caspase-8 than is caspase-8 itself...
  31. pmc Structural and kinetic determinants of protease substrates
    John C Timmer
    Apoptosis and Cell Death Research Program at the Burnham Institute for Medical Research, La Jolla, California, USA
    Nat Struct Mol Biol 16:1101-8. 2009
    ..This unique combination of proteomics, biochemistry, kinetics and substrate engineering reveals new insights into the structure-function relationship of protease targets and their validation from large-scale approaches...
  32. doi request reprint Expression, purification, and characterization of caspases
    Jean Bernard Denault
    The Burnham Institute, La Jolla, California, USA
    Curr Protoc Protein Sci . 2003
    ..Specific details for the expression, purification of caspase-3, -6, -7, -8, -9 and -10 are discussed along with strategies to obtain particular forms (e.g., the zymogen) of some of them...
  33. ncbi request reprint Identification of proteolytic cleavage sites by quantitative proteomics
    Mari Enoksson
    Burnham Institute for Medical Research, La Jolla, California 92037, USA
    J Proteome Res 6:2850-8. 2007
    ..Moreover, we were able to identify proteolytic cleavage products associated with the induction of cell-free apoptosis. Together, these data reveal a novel application for iTRAQ technology for the detection of proteolytic substrates...
  34. pmc Human caspases: activation, specificity, and regulation
    Cristina Pop
    Program in Apoptosis and Cell Death Research, Burnham Institute for Medical Research, La Jolla, California 92037, USA
    J Biol Chem 284:21777-81. 2009
    ..We also delineate substantial gaps in knowledge of caspase function, which can be approached by techniques and experimental paradigms that are currently undergoing development...
  35. pmc Comparative analysis of apoptosis and inflammation genes of mice and humans
    John C Reed
    The Burnham Institute, La Jolla, California 92037, USA
    Genome Res 13:1376-88. 2003
    ..With this caveat, we discuss similarities and differences in human and murine genes from these domain families...
  36. doi request reprint Caspases
    Jean Bernard Denault
    The Burnham Institute, La Jolla, California, USA
    Curr Protoc Protein Sci . 2002
    ..It is intended to be an overview for investigators that are unfamiliar with this family of enzymes but it is also applicable to scientists pursuing research in this field...
  37. doi request reprint Caspase assays: identifying caspase activity and substrates in vitro and in vivo
    Cristina Pop
    Program in Apoptosis and Cell Death Research, The Burnham Institute for Medical Research, La Jolla, California, USA
    Methods Enzymol 446:351-67. 2008
    ..We also recommend methods for working with recombinant initiator caspases in vitro and suggest ways to accurately assess the cleavage efficiency of natural caspase substrates...
  38. ncbi request reprint Sequential autolytic processing activates the zymogen of Arg-gingipain
    Jowita Mikolajczyk
    Burnham Institute, La Jolla, California 92037, USA
    J Biol Chem 278:10458-64. 2003
    ..Each step in activation requires the previous step, and an affinity probe reveals that incremental activity enhancements are achieved in a stepwise manner...
  39. pmc Caspase 3 attenuates XIAP (X-linked inhibitor of apoptosis protein)-mediated inhibition of caspase 9
    Jean Bernard Denault
    Program in Cell Death and Apoptosis Research, The Burnham Institute for Medical Research and the Graduate Program in Molecular Pathology, University of California San Diego, La Jolla, CA 92037, USA
    Biochem J 405:11-9. 2007
    ..Our results demonstrate that cleavage by caspase 3 does not activate caspase 9, but enhances apoptosis by alleviating XIAP inhibition of the apical caspase...
  40. pmc Vaccinia virus protein F1L is a caspase-9 inhibitor
    Dayong Zhai
    Sanford Burnham Medical Research Institute, La Jolla, California 92037, USA
    J Biol Chem 285:5569-80. 2010
    ....
  41. ncbi request reprint Apoptotic caspase activation and activity
    Jean Bernard Denault
    The Burnham Institute for Medical Research, La Jolla, CA, USA
    Methods Mol Biol 414:191-220. 2008
    ..This chapter describes some of the methods used by our group to study the activation mechanisms of caspases and their activity...
  42. ncbi request reprint Caspases: keys in the ignition of cell death
    Jean Bernard Denault
    Program in Apoptosis and Cell Death Research, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
    Chem Rev 102:4489-500. 2002
  43. pmc Profiling constitutive proteolytic events in vivo
    John C Timmer
    Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Biochem J 407:41-8. 2007
    ..Taken together, our results demonstrate how to rapidly distinguish real proteolysis that occurs in vivo from the predictions based on in vitro experiments...
  44. pmc Identification of ubiquitination sites on the X-linked inhibitor of apoptosis protein
    Hwain Shin
    The Program in Apoptosis and Cell Death Research, Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Biochem J 373:965-71. 2003
    ..Our data firmly locate the auto-ubiquitination sites, and raise doubts regarding the importance of this event as a mechanism for regulating the levels of XIAP...
  45. pmc Streptolysin O promotes group A Streptococcus immune evasion by accelerated macrophage apoptosis
    Anjuli M Timmer
    Department of Pediatrics, Biomedical Sciences Graduate Program, Laboratory of Signal Transduction, University of California, San Diego, La Jolla, California 92093, USA
    J Biol Chem 284:862-71. 2009
    ..We conclude that accelerated, caspase-dependent macrophage apoptosis induced by the pore-forming cytolysin SLO contributes to GAS immune evasion and virulence...
  46. ncbi request reprint Yersinia phosphatase induces mitochondrially dependent apoptosis of T cells
    Shane Bruckner
    Program of Inflammation, Infectious and Inflammatory Disease Center, Cancer Center, The Burnham Institute, La Jolla, California 92037, USA
    J Biol Chem 280:10388-94. 2005
    ..We conclude that YopH not only paralyzes T cells acutely, but also ensures that the cells will not recover to induce a protective immune response but instead undergo mitochondrially regulated programmed cell death...
  47. ncbi request reprint IAP proteins: blocking the road to death's door
    Guy S Salvesen
    Program in Apoptosis and Cell Death Research, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
    Nat Rev Mol Cell Biol 3:401-10. 2002
    ..Here, we review the functional and structural properties of this fascinating group of proteins, and of several recently identified IAP-binding factors that regulate IAP function...
  48. pmc Structure of the Fas/FADD complex: a conditional death domain complex mediating signaling by receptor clustering
    Guy S Salvesen
    The Burnham Institute for Medical Research, La Jolla, CA 92037, USA
    Cell Cycle 8:2723-7. 2009
    ..This model portrays how sole death domains are able to mediate signaling upon receptor clustering in the complete absence of enzyme activity...
  49. ncbi request reprint Early processing of Bid and caspase-6, -8, -10, -14 in the canine brain during cardiac arrest and resuscitation
    Maryla Krajewska
    The Burnham Institute, La Jolla, CA 92037, USA
    Exp Neurol 189:261-79. 2004
    ....
  50. ncbi request reprint Characteristics of the caspase-like catalytic domain of human paracaspase
    Scott J Snipas
    Program in Apoptosis and Cell Death Research, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Biol Chem 385:1093-8. 2004
    ..We suggest a switch in the use of catalytic residues to generate an enzyme overlapping the canonical clan CD protease active site...
  51. pmc Emerging principles in protease-based drug discovery
    Marcin Drag
    Program in Apoptosis and Cell Death Research, Burnham Institute for Medical Research, La Jolla, California 92037, USA
    Nat Rev Drug Discov 9:690-701. 2010
    ....
  52. ncbi request reprint Caspases and neuronal development
    Ciara A Ryan
    Program in Apoptosis and Cell Death Research, The Burnham Institute, La Jolla, CA 92037, USA
    Biol Chem 384:855-61. 2003
    ..In addition, we present data supporting this hypothesis...
  53. ncbi request reprint Apoptosome: the seven-spoked death machine
    Guy S Salvesen
    Program in Apoptosis and Cell Death Research, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Dev Cell 2:256-7. 2002
    ..This structure explains the assembly of the machine, the tentative location of the subcomponents, and proposes a mechanism for initiating the death signal...
  54. pmc Human inhibitor of apoptosis proteins: why XIAP is the black sheep of the family
    Brendan P Eckelman
    Burnham Institute for Medical Research, La Jolla, California 92037, USA
    EMBO Rep 7:988-94. 2006
    ....
  55. ncbi request reprint Activity-based probes that target diverse cysteine protease families
    Daisuke Kato
    Department of Pathology, Stanford University School of Medicine, 300 Pasteur Dr, Stanford, California, USA
    Nat Chem Biol 1:33-8. 2005
    ..Biochemical studies using these reagents highlight their overall utility and provide insight into the biochemical functions of members of these protease families...
  56. ncbi request reprint Glycosylation broadens the substrate profile of membrane type 1 matrix metalloproteinase
    Yi I Wu
    Department of Cell and Molecular Biology and Division of Hematology Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
    J Biol Chem 279:8278-89. 2004
    ..These data provide evidence for an additional mechanism for post-translational control of MT1-MMP activity and suggest that glycosylation of MT1-MMP may regulate its substrate targeting...
  57. ncbi request reprint Neutralization of Smac/Diablo by inhibitors of apoptosis (IAPs). A caspase-independent mechanism for apoptotic inhibition
    John C Wilkinson
    Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA
    J Biol Chem 279:51082-90. 2004
    ..These data show that cytoprotective IAPs can inhibit apoptosis through the neutralization of IAP antagonists, rather than by directly inhibiting caspases...
  58. ncbi request reprint An IAP-IAP complex inhibits apoptosis
    Takehiko Dohi
    Department of Cancer Biology and the Cancer Center, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA
    J Biol Chem 279:34087-90. 2004
    ..Therefore, orchestration of an IAP-IAP complex regulates apoptosis...
  59. ncbi request reprint Selective disruption of lysosomes in HeLa cells triggers apoptosis mediated by cleavage of Bid by multiple papain-like lysosomal cathepsins
    Tina Cirman
    Department of Biochemistry and Molecular Biology, Jozef Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia
    J Biol Chem 279:3578-87. 2004
    ..Incubation of full-length Bid treated with cathepsins B, H, L, and S resulted in rapid cytochrome c release from isolated mitochondria. Thus, Bid may be an important mediator of apoptosis induced by lysosomal disruption...
  60. ncbi request reprint Direct cleavage of AMPA receptor subunit GluR1 and suppression of AMPA currents by caspase-3: implications for synaptic plasticity and excitotoxic neuronal death
    Chengbiao Lu
    Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, Baltimore, MD 21224, USA
    Neuromolecular Med 1:69-79. 2002
    ....
  61. pmc The protein structures that shape caspase activity, specificity, activation and inhibition
    Pablo Fuentes-Prior
    Abteilung Strukturforschung, Max Planck Institut fur Biochemie, Am Klopferspitz 18a, D82152, Planegg Martinsried, Germany
    Biochem J 384:201-32. 2004
    ..We present a comprehensive review of the caspases, their regulators and inhibitors from a structural and mechanistic point of view, and with an aim to consolidate the many threads that define the rapid growth of this field...
  62. pmc Engineering ML-IAP to produce an extraordinarily potent caspase 9 inhibitor: implications for Smac-dependent anti-apoptotic activity of ML-IAP
    Domagoj Vucic
    Department of Molecular Oncology, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA
    Biochem J 385:11-20. 2005
    ..These results suggest that ML-IAP might regulate apoptosis by sequestering Smac and preventing it from antagonizing XIAP-mediated inhibition of caspases, rather than by direct inhibition of caspases...
  63. ncbi request reprint Caspases: opening the boxes and interpreting the arrows
    Guy S Salvesen
    Cell Death Differ 9:3-5. 2002
  64. pmc Activation-coupled membrane-type 1 matrix metalloproteinase membrane trafficking
    Yi I Wu
    Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
    Biochem J 407:171-7. 2007
    ....
  65. ncbi request reprint Identification of early intermediates of caspase activation using selective inhibitors and activity-based probes
    Alicia B Berger
    Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, USA
    Mol Cell 23:509-21. 2006
    ..Our data suggest that caspase-7 activation proceeds through a previously uncharacterized intermediate that is formed without cleavage of the intact zymogen...
  66. ncbi request reprint Lack of involvement of strand s1'A of the viral serpin CrmA in anti-apoptotic or caspase-inhibitory functions
    Miljan Simonovic
    Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, USA
    Arch Biochem Biophys 440:1-9. 2005
    ..Thus, although the 51-56 region of CrmA is unique, and is exposed and highly susceptible to proteolysis, any in vivo role must involve a function other than proteinase inhibition or cell sparing...
  67. ncbi request reprint Reprieval from execution: the molecular basis of caspase inhibition
    Henning R Stennicke
    The Finsen Laboratory, Copenhagen University Hospital, Strandboulevarden 49, DK 2100 Copenhagen, Denmark
    Trends Biochem Sci 27:94-101. 2002
    ..This article reviews the newly defined molecular basis for the regulation of the caspases by viral and endogenous inhibitors...
  68. ncbi request reprint Chemical ligation--an unusual paradigm in protease inhibition
    Henning R Stennicke
    Department for Haemostasis Biochemistry, Biopharmaceuticals Research Unit, Novo Nordisk, Novo Nordisk Park, DK 2760 Måløv, Denmark
    Mol Cell 21:727-8. 2006
    ..A recent paper in Chemistry and Biology (Lu et al., 2006) demonstrates a curious mechanism of inhibition of a caspase, relying on principles of native peptide ligation...
  69. ncbi request reprint Regulating cysteine protease activity: essential role of protease inhibitors as guardians and regulators
    Boris Turk
    Department of Biochemistry and Molecular Biology, J Stefan Institute, Ljubljana, Slovenia
    Curr Pharm Des 8:1623-37. 2002
    ..In this review the basic principles of physiological protease inhibition by protein inhibitors are discussed with the focus on papain-like lysosomal cysteine proteases and the caspases, and their inhibitors...
  70. ncbi request reprint Carboxyl-terminal proteolytic processing of CUX1 by a caspase enables transcriptional activation in proliferating cells
    Mary Truscott
    Molecular Oncology Group, McGill University Health Center, Montreal, Quebec H3A 1A1, Canada
    J Biol Chem 282:30216-26. 2007
    ..Together, our results identify a substrate of caspases in proliferating cells and suggest a mechanism by which caspases can accelerate cell cycle progression...
  71. ncbi request reprint Small molecules not direct activators of caspases
    Jean Bernard Denault
    Nat Chem Biol 3:519; author reply 520. 2007
  72. ncbi request reprint Design, synthesis, and evaluation of aza-peptide epoxides as selective and potent inhibitors of caspases-1, -3, -6, and -8
    Karen Ellis James
    School of Chemistry and Biochemistry and the Parker H Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia 30332 0400, USA
    J Med Chem 47:1553-74. 2004
    ....
  73. ncbi request reprint Aza-peptide Michael acceptors: a new class of inhibitors specific for caspases and other clan CD cysteine proteases
    Ozlem Dogan Ekici
    School of Chemistry and Biochemistry and the Parker H Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332 0400, USA
    J Med Chem 47:1889-92. 2004
    ..Aza-Lys and aza-Orn derivatives were potent inhibitors of gingipain K and clostripain. Aza-peptide Michael acceptors showed no cross reactivity toward papain, cathepsin B, and calpain...
  74. pmc XIAP-mediated caspase inhibition in Hodgkin's lymphoma-derived B cells
    Hamid Kashkar
    Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Goldenfelsstrasse 19 21, 50935 Cologne, Germany
    J Exp Med 198:341-7. 2003
    ..The results of this paper suggest that high level XIAP expression is a hallmark of HL, which may play a crucial role in resistance to apoptosis...
  75. ncbi request reprint Caspases on the brain
    Carol M Troy
    Department of Pathology and Taub Institute for the Study of Alzheimer s Disease and the Aging Brain, Columbia University College of Physicians and Surgeons, New York, New York, USA
    J Neurosci Res 69:145-50. 2002
    ..In this Mini-Review, we consider the current status of the basic control mechanisms and how these may be subverted during neurodegeneration...
  76. ncbi request reprint A novel caspase-7 specific monoclonal antibody
    Uros Gregorc
    Immunol Lett 98:167-9. 2005
  77. doi request reprint Cysteine cathepsins trigger caspase-dependent cell death through cleavage of bid and antiapoptotic Bcl-2 homologues
    Gabriela Droga-Mazovec
    Department of Biochemistry, Molecular and Structural Biology, J Stefan Institute, Sl 1000 Ljubljana, Slovenia
    J Biol Chem 283:19140-50. 2008
    ..Moreover, XIAP (X-chromosome-linked inhibitor of apoptosis) was also found to be a target of cysteine cathepsins, suggesting that cathepsins can mediate caspase-dependent apoptosis also downstream of mitochondria...
  78. ncbi request reprint Aza-peptide epoxides: a new class of inhibitors selective for clan CD cysteine proteases
    Juliana L Asgian
    School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta 30332 0400, USA
    J Med Chem 45:4958-60. 2002
    ..The aza-Asn derivatives are effective legumain inhibitors, while the aza-Asp epoxides were specific for caspases. The inhibitors have little or no inhibition with other proteases such as chymotrypsin, papain, or cathepsin B...
  79. ncbi request reprint Ionomycin-activated calpain triggers apoptosis. A probable role for Bcl-2 family members
    Shirley Gil-Parrado
    Abteilung für Klinische Chemie und Klinische Biochemie, Chirurgische Klinik Innenstadt, Klinikum der LMU München, Nussbaumstrasse 20, D 80336 Munich, Germany
    J Biol Chem 277:27217-26. 2002
    ..We conclude that ionomycin-induced calpain activation promotes decrease of Bcl-2 proteins thereby triggering the intrinsic apoptotic pathway...

Research Grants31

  1. INHIBITION OF PROTEASES BY IAPS
    Guy Salvesen; Fiscal Year: 2001
    ....
  2. Apoptosis: Basic Mechanisms and Disease Relevance
    Guy Salvesen; Fiscal Year: 2003
    ..of experienced and highly active apoptosis researchers at the Burnham Institute (John Reed, Dale Bredesen, Guy Salvesen, Steven Frisch, Erkki Ruoslahti, Kathryn Ely, Nuria Assa-Munt and Stuart Lipton) and the nearby La Jolla ..
  3. PROTEASES IN NEURONAL CELL DEATH
    Guy Salvesen; Fiscal Year: 2003
    ....
  4. PROTEINASE INHIBITORY MECHANISMS OF SERPINS
    Guy Salvesen; Fiscal Year: 2003
    ....
  5. PROTEASES IN NEURONAL CELL DEATH
    Guy Salvesen; Fiscal Year: 2004
    ....
  6. ASPIC, a novel MS technology, applied to degradomics
    Guy Salvesen; Fiscal Year: 2004
    ..Phase II will use the optimized technology to determine the proteases and protease substrates that constitute the signaling pathways during (i) apoptosis of HEK293 cells and (ii) T-cell activation. ..
  7. PROTEASES IN NEURONAL CELL DEATH
    Guy Salvesen; Fiscal Year: 2005
    ....
  8. ASPIC, a novel MS technology, applied to degradomics
    Guy Salvesen; Fiscal Year: 2005
    ..Phase II will use the optimized technology to determine the proteases and protease substrates that constitute the signaling pathways during (i) apoptosis of HEK293 cells and (ii) T-cell activation. ..
  9. PROTEASES IN NEURONAL CELL DEATH
    Guy Salvesen; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  10. PROTEASES IN NEURONAL CELL DEATH
    Guy Salvesen; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  11. Development of a High-Throughput Assay for Human Desumoylating Enzymes [SENPs]
    Guy Salvesen; Fiscal Year: 2007
    ..The assays are expected to provide a tool for the rapid development of chemical probes for members of the family. [unreadable] [unreadable] [unreadable]..
  12. INHIBITION OF PROTEASES BY IAPS
    Guy Salvesen; Fiscal Year: 2002
    ..abstract_text> ..
  13. PROTEINASE INHIBITORY MECHANISMS OF SERPINS
    Guy Salvesen; Fiscal Year: 2002
    ....
  14. PROTEASES IN NEURONAL CELL DEATH
    Guy Salvesen; Fiscal Year: 2001
    ..It will determine the requirements for activity of caspases that execute apoptosis, and then test the hypothesis that the disease-causing effect Alzheimer's Disease is due to apoptosis inappropriately triggered by lysosomal disruption. ..
  15. PROTEASES IN NEURONAL CELL DEATH
    Guy Salvesen; Fiscal Year: 1999
    ..It will determine the requirements for activity of caspases that execute apoptosis, and then test the hypothesis that the disease-causing effect Alzheimer's Disease is due to apoptosis inappropriately triggered by lysosomal disruption. ..
  16. PROTEINASE INHIBITORY MECHANISMS OF SERPINS
    Guy Salvesen; Fiscal Year: 1999
    ..We will test the constructs for inhibition of target proteinases, for thermodynamic stability and structural integrity. ..
  17. INHIBITION OF PROTEASES BY IAPS
    Guy Salvesen; Fiscal Year: 1999
    ....
  18. INHIBITION OF PROTEASES BY IAPS
    Guy Salvesen; Fiscal Year: 2000
    ....
  19. PROTEASES IN NEURONAL CELL DEATH
    Guy Salvesen; Fiscal Year: 2000
    ..It will determine the requirements for activity of caspases that execute apoptosis, and then test the hypothesis that the disease-causing effect Alzheimer's Disease is due to apoptosis inappropriately triggered by lysosomal disruption. ..
  20. PROTEINASE INHIBITORY MECHANISMS OF SERPINS
    Guy Salvesen; Fiscal Year: 2000
    ....
  21. PROTEINASE INHIBITORY MECHANISMS OF SERPINS
    Guy Salvesen; Fiscal Year: 2001
    ....
  22. 2008 Cell Death Gordon Research Conference
    Guy Salvesen; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable] [unreadable]..