Research Topics
Species | Guy SalvesenSummaryAffiliation: The Burnham Institute Country: USA Publications
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Publications
Caspase 8: igniting the death machineG 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...- Caspases and apoptosisGuy 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... 
Caspase mechanismsGuy 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....- Caspase activation - stepping on the gas or releasing the brakes? Lessons from humans and fliesGuy 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... - Role of proteolysis in caspase-8 activation and stabilizationCristina 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... - Human caspase-7 activity and regulation by its N-terminal peptideJean 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... - The apoptosome activates caspase-9 by dimerizationCristina 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.... 
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...- Engineered hybrid dimers: tracking the activation pathway of caspase-7Jean-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... - Small-molecule antagonists of apoptosis suppressor XIAP exhibit broad antitumor activityAaron 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... - XIAP inhibits caspase-3 and -7 using two binding sites: evolutionarily conserved mechanism of IAPsFiona 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... - Activation and substrate specificity of caspase-14Jowita 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... - A unified model for apical caspase activationKelly 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... - The human anti-apoptotic proteins cIAP1 and cIAP2 bind but do not inhibit caspasesBrendan 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... - Dominant-interfering forms of MEF2 generated by caspase cleavage contribute to NMDA-induced neuronal apoptosisShu 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... - Nicotinamide rescues human embryonic stem cell-derived neuroectoderm from parthanatic cell deathFlavio 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... - Caspase-8 cleaves histone deacetylase 7 and abolishes its transcription repressor functionFiona 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... - The BIR domain of IAP-like protein 2 is conformationally unstable: implications for caspase inhibitionHwain 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... - Aminopeptidase fingerprints, an integrated approach for identification of good substrates and optimal inhibitorsMarcin 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.... - The apoptosome: signalling platform of cell deathStefan 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... - Mechanisms of caspase activationKelly 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... - Small ubiquitin-related modifier (SUMO)-specific proteases: profiling the specificities and activities of human SENPsJowita 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... - Activity profiling of human deSUMOylating enzymes (SENPs) with synthetic substrates suggests an unexpected specificity of two newly characterized members of the familyMarcin 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... - DeSUMOylating enzymes--SENPsMarcin 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... - Inhibitor specificity of recombinant and endogenous caspase-9Ciara 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... - Human caspases: activation, specificity, and regulationCristina 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... - The nematode death machine in 3DCristina 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... - Activation and specificity of human caspase-10Katherine 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.... - Transnitrosylation of XIAP regulates caspase-dependent neuronal cell deathTomohiro 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... - Transferring death: a role for tRNA in apoptosis regulationBram 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... - Identification of proteolytic cleavage sites by quantitative proteomicsMari 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... - 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... - Structural and kinetic determinants of protease substratesJohn 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... - Expression, purification, and characterization of caspasesJean-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... - Comparative analysis of apoptosis and inflammation genes of mice and humansJohn 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... - Caspase assays: identifying caspase activity and substrates in vitro and in vivoCristina 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... - CaspasesJean-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... - Sequential autolytic processing activates the zymogen of Arg-gingipainJowita 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... - Caspase 3 attenuates XIAP (X-linked inhibitor of apoptosis protein)-mediated inhibition of caspase 9Jean 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... - Vaccinia virus protein F1L is a caspase-9 inhibitorDayong Zhai
Sanford Burnham Medical Research Institute, La Jolla, California 92037, USA
J Biol Chem 285:5569-80. 2010.... - Apoptotic caspase activation and activityJean 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... - Caspases: keys in the ignition of cell deathJean-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 - Profiling constitutive proteolytic events in vivoJohn 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... - Identification of ubiquitination sites on the X-linked inhibitor of apoptosis proteinHwain 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... - Streptolysin O promotes group A Streptococcus immune evasion by accelerated macrophage apoptosisAnjuli 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... - Yersinia phosphatase induces mitochondrially dependent apoptosis of T cellsShane 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... - IAP proteins: blocking the road to death's doorGuy 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... - Structure of the Fas/FADD complex: a conditional death domain complex mediating signaling by receptor clusteringGuy 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... - Early processing of Bid and caspase-6, -8, -10, -14 in the canine brain during cardiac arrest and resuscitationMaryla Krajewska
The Burnham Institute, La Jolla, CA 92037, USA
Exp Neurol 189:261-79. 2004.... - Characteristics of the caspase-like catalytic domain of human paracaspaseScott 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... - Emerging principles in protease-based drug discoveryMarcin 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.... - Caspases and neuronal developmentCiara 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... - Apoptosome: the seven-spoked death machineGuy 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... - Human inhibitor of apoptosis proteins: why XIAP is the black sheep of the familyBrendan P Eckelman
Burnham Institute for Medical Research, La Jolla, California 92037, USA
EMBO Rep 7:988-94. 2006.... - Activity-based probes that target diverse cysteine protease familiesDaisuke 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... - Glycosylation broadens the substrate profile of membrane type 1 matrix metalloproteinaseYi 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... - Neutralization of Smac/Diablo by inhibitors of apoptosis (IAPs). A caspase-independent mechanism for apoptotic inhibitionJohn 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... - An IAP-IAP complex inhibits apoptosisTakehiko 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... - Selective disruption of lysosomes in HeLa cells triggers apoptosis mediated by cleavage of Bid by multiple papain-like lysosomal cathepsinsTina 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... - Direct cleavage of AMPA receptor subunit GluR1 and suppression of AMPA currents by caspase-3: implications for synaptic plasticity and excitotoxic neuronal deathChengbiao Lu
Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, Baltimore, MD 21224, USA
Neuromolecular Med 1:69-79. 2002.... - The protein structures that shape caspase activity, specificity, activation and inhibitionPablo 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... - Engineering ML-IAP to produce an extraordinarily potent caspase 9 inhibitor: implications for Smac-dependent anti-apoptotic activity of ML-IAPDomagoj 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... - Caspases: opening the boxes and interpreting the arrowsGuy S Salvesen
Cell Death Differ 9:3-5. 2002 - Activation-coupled membrane-type 1 matrix metalloproteinase membrane traffickingYi I Wu
Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Biochem J 407:171-7. 2007.... - Identification of early intermediates of caspase activation using selective inhibitors and activity-based probesAlicia 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... - Lack of involvement of strand s1'A of the viral serpin CrmA in anti-apoptotic or caspase-inhibitory functionsMiljan 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... - Reprieval from execution: the molecular basis of caspase inhibitionHenning 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... - Chemical ligation--an unusual paradigm in protease inhibitionHenning R Stennicke
Department for Haemostasis Biochemistry, Biopharmaceuticals Research Unit, Novo Nordisk, Novo Nordisk Park, , 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... - Regulating cysteine protease activity: essential role of protease inhibitors as guardians and regulatorsBoris 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... - Carboxyl-terminal proteolytic processing of CUX1 by a caspase enables transcriptional activation in proliferating cellsMary 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... - Small molecules not direct activators of caspasesJean-Bernard Denault
Nat Chem Biol 3:519; author reply 520. 2007 - Design, synthesis, and evaluation of aza-peptide epoxides as selective and potent inhibitors of caspases-1, -3, -6, and -8Karen 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.... - Aza-peptide Michael acceptors: a new class of inhibitors specific for caspases and other clan CD cysteine proteasesOzlem 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... 
XIAP-mediated caspase inhibition in Hodgkin's lymphoma-derived B cellsHamid 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...- Caspases on the brainCarol 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... - A novel caspase-7 specific monoclonal antibodyUros Gregorc
Immunol Lett 98:167-9. 2005 - Cysteine cathepsins trigger caspase-dependent cell death through cleavage of bid and antiapoptotic Bcl-2 homologuesGabriela 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... - Aza-peptide epoxides: a new class of inhibitors selective for clan CD cysteine proteasesJuliana 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... - Ionomycin-activated calpain triggers apoptosis. A probable role for Bcl-2 family membersShirley 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 Grants
- INHIBITION OF PROTEASES BY IAPSGuy Salvesen; Fiscal Year: 2001....
- Apoptosis: Basic Mechanisms and Disease RelevanceGuy 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 ..
- PROTEINASE INHIBITORY MECHANISMS OF SERPINSGuy Salvesen; Fiscal Year: 2003....
- ASPIC, a novel MS technology, applied to degradomicsGuy 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. ..
- PROTEASES IN NEURONAL CELL DEATHGuy Salvesen; Fiscal Year: 2007....
- 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. ..
- INHIBITION OF PROTEASES BY IAPSGuy Salvesen; Fiscal Year: 2002..abstract_text> ..
- PROTEASES IN NEURONAL CELL DEATHGuy 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. ..
- PROTEINASE INHIBITORY MECHANISMS OF SERPINSGuy Salvesen; Fiscal Year: 1999..We will test the constructs for inhibition of target proteinases, for thermodynamic stability and structural integrity. ..