Caspases : their role in cell death and cell survival / [edited by] Marek Los, Henning Walczak.

Format:

Book

Contributor:

Los, Marek, MD

Walczak, Henning.

Series:

Molecular biology intelligence unit ; 24.

Molecular biology intelligence unit ; 24

Language:

English

Subjects (All):

Aspartic proteinases.

Apoptosis.

Physical Description:

253 pages, 3 unnumbered pages of plates : illustrations (some color) ; 24 cm.

Place of Publication:

Georgetown, Tex., U.S.A. : Landes Bioscience ; New York, N.Y., U.S.A. : Kluwer Academic/Plenum Pub., [2002]

Summary:

The volume offers insight into the key research topics that involve caspases. Leading experts from various areas of biology and medicine have compiled this volume so that both the novice and the professional will use this as the main reference for caspases for years to come. The reader will learn about the role of caspases in apoptosis signaling, inflammation and cancer therapy while being updated on the methodology used to study caspases and the efforts of pharmaceutical research in targeting caspases.

Contents:

1. The Caspase Family / Mohamed Lamkanfi, Wim Declercq, Bart Depuydt, Michael Kalai, Xavier Saelens, Peter Vandenabeele 1

Primary Structure of Caspases 2

Pro Caspase Maturation 3

Three-Dimensional Structure of Mature Caspases 6

Catalytic Mechanism 9

Caspase Prodomains 11

Caspase Splice Variants 12

Caspase Substrates 14

Synthetic Peptide Substrates and Site Preferences of Human Caspases 19

Caspase Inhibitors 20

Phylogenetic Analysis of the Caspases 24

2. Caspase Cascades in Apoptosis / Colin Adrain, Emma M. Creagh, Seamus J. Martin 41

Caspases: Molecular Wrecking Balls 41

Caspase Activation Pathways: Getting the Wrecking Ball Rolling 42

Caspase Activation Cascades: A Trickle Becomes a Flood 42

Coordinating the Demolition: Foremen and Laborers 43

The Cytochrome c / Apaf-1-Initiated Caspase Cascade 44

Initiator and Executioner Caspases: Blurring the Distinctions 44

The Roads to Ruin Beyond the DISC 46

The Granzyme B-Initiated Caspase Cascade 46

Lonely Caspase Seeks Others for Meaningful Cascade 47

3. Caspase Activation at the TNF-R Family Members Death Inducing Signaling Complexes (DISCs) / Martin R. Sprick, Henning Walczak 53

Identification of "Tumor Necrosis Factor" 53

The Death Ligands 54

The Death Receptors 54

Biochemistry of TNF and TNFR Interactions 55

Identification of CD95 (APO-1/Fas) Apoptosis System 55

Identification of the TRAIL (APO-2L) Apoptosis System 56

Initializing Death: Formation of the Death Inducing Signaling Complex (DISC) 57

DISC Components and Mode of DISC Assembly 58

The Initiator Caspases 59

Mechanism of Caspase Activation at the DISC 61

Activation of the Initiator Caspases 8 and 10 62

Caspase Inhibition by cFLIP 63

Spreading the Fire 63

The Step-Sisters of the DISC 65

TRADD and TNF-R DISC Assembly 65

Other DD-Containing Receptors 66

Final Words and Reflections 66

4. Mitochondrial/Apoptosome Dependent Activation of Caspases / Kelvin Cain 73

Mechanisms of Caspase Activation 74

Primitive Apoptosomes 78

The Mammalian Apoptosome 78

Regulation and Modulation of the Apoptosome 85

5. Modulation of Caspase Activity by Cellular Inhibitors / Klaus W. Wagner, Badry D. Bursulaya, Quinn L. Deveraux 91

The Inhibitor of Apoptosis (IAP) Protein Family 92

Cellular FLIP 100

6. Virus-Encoded Caspase Inhibitors / Grant McFadden, Richard W. Moyer 105

CrmA:/SPI-2-Family: A Poxvirus Encoded Inhibitory Serpins and Caspase Inhibitors 106

Viral Inhibitor of Apoptosis Proteins (vIAPs) 113

P35 115

7. Apoptosis Dependent and Independent Functions of Caspases / Alicia Algeciras-Schimnich, Bryan C. Barnhart, Marcus E. Peter 123

Regulation of Apoptosis by a Combination of Initiator and Effector Caspases 123

Role of Caspases in Development, Cell Proliferation and Cell Cycle 125

Inactivation of Survival Pathways by Caspases 127

Caspases in Cell Spreading and Migration 129

Novel Function of Caspases: Role in Receptor Internalization 129

8. The Role of Caspases in Modulation of Cytokines and other Molecules in Apoptosis and Inflammation / Harald Loppnow, Krzysztof Guzik, Juliusz Pryjma 135

The Role of Caspases in Modulation of Activity of Cytokines 135

Caspase-Dependent Modulation of Cytokine Production 138

Regulation of Cytokine Processing by Caspases 138

Caspase-1, IL-1 and Apoptosis 139

Cytokines both Augment and Block Caspase-Dependent Apoptosis 140

Caspases in the Regulation of Transcription 141

9. Caspases, Bcl-2 Family Proteins and Other Components of the Death Machinery: Their Role in the Regulation of the Immune Response / Marc Pellegrini, Andreas Strasser 155

Overview of the Immune System 156

Overview of the Apoptotic Program, the Operating System and Caspases 157

The Caspase Hardware 161

Deciphering the Operating Language of the Apoptotic Program in the Immune System 161

When the Program Crashes or is Corrupted 163

Infectious Diseases 165

10. Learning from Deficiency: Gene Targeting of Caspases / Timothy S. Zheng 175

Overview of Caspase Deficient Mice 175

Caspases in Apoptosis Execution 178

The Plasticity of Caspase Activation 179

Caspase Beyond Death 180

Future Perspectives 180

11. Caspase Activation in Cancer Therapy / Simone Fulda, Klaus-Michael Debatin 185

Caspases as Central Death Effector Molecules 186

Pathways of Caspase Activation 186

Signaling Pathways in Cancer Therapy 188

Regulation of Caspase Activation 189

Caspase-Independent Cell Death 190

Role of Caspases for Treatment Response in vivo 191

12. In Situ Activation of Caspases Revealed by Affinity Labeling Their Enzymatic Sites / Jerzy Grabarek, Zbigniew Darzynkiewicz 197

Affinity Labeling of Enzyme Centers with FLICA 198

Subcellular Localization of FLICA-Binding Sites 199

Detection of Caspase Activation Combined with Other Probes of Apoptosis 200

Stathmo-Apoptosis: The Use of FLICA to Arrest the Process of Apoptosis 203

13. Other Methods of Caspase Activity Monitoring / Hubert Hug, Christof Burek, Marek Los 211

Theoretical Background 211

Detection of Caspase Activation by Western Blot 212

Fluorescent Measurement of Caspase Activity in Intact Cells 215

Detection of Caspase Activity in Cell Extracts 217

14. Caspases as Targets for Drug Development / Manuela Michalke, Anna Stepczynska, Malgorzata Burek, Truc Nguyen Bui, Karin Loser, Krzysztof Krzemieniecki, Marek Los 221

Modulation of Caspase Activity, Implications for Apoptosis and Cytokine Maturation 225

Modulation of the Mitochondrial Death Pathway: Pro- and Antiapoptotic Bcl-2 Family Members and Their Perspectives in the Clinic 227

How to Control Already-Activated Caspases?

IAPs, Smac/DIABLO and Omi/HtrA2 229

Receptor-Mediated PCD

Prospects and Limitations 231

Perspectives 231

15. Caspase-Independent Cell Death Mechanisms / Donat Kogel, Jochen H. M. Prehn 237

Multiple Forms of PCD 237

Caspase-Independent PCD Controlled by Bcl-2 Family Proteins 238

Studies Using Caspase Inhibitors 239

Mitochondrial Dysfunction Due to Loss of Cytochrome c 240

Role of Other Proapoptotic Factors Released from Mitochondria in a Bcl-2-Dependent Manner 241

Caspase-Independent Cell Death in Response to Death Receptor Signaling 241

Necrosis Controlled by Bcl-2 Family Members 242

Involvement of Non-Caspase Proteases in PCD 243

Oncogenic Transformation: Escape from PCD 243.

Notes:

Includes bibliographical references and index.

ISBN:

0306474417

OCLC:

51306071