Signalling Pathways in Apoptosis (Modern Genetics, Vol. 5)

BOOK COVER......Page 1
HALF-TITLE......Page 2
TITLE......Page 4
COPYRIGHT......Page 5
CONTENTS......Page 6
PREFACE TO THE SERIES......Page 8
PREFACE......Page 9
CONTRIBUTORS......Page 10
OVERVIEW: A MATTER OF LIFE AND DEATH......Page 16
TRANSCRIPTIONAL REGULATION OF APOPTOSIS......Page 17
THE BCL-2 FAMILY......Page 19
CASPASES......Page 23
THE TNF-A/FAS PATHWAY OF APOPTOSIS......Page 26
REFERENCES......Page 31
Part 1 INDUCERS OF APOPTOSIS......Page 46
INTRODUCTION......Page 47
THE DEATH LIGANDS......Page 49
The CD95 system......Page 50
The TNF system......Page 54
DEATH RECEPTOR-ASSOCIATING MOLECULES......Page 56
THE DEATH-INDUCING SIGNALLING COMPLEX (DISC)......Page 59
EFFECTOR CASPASES......Page 61
Role of non-caspase proteases......Page 64
The sphingomyelin pathway......Page 65
Stress-activated protein kinases......Page 67
Reactive oxygen intermediates: necrosis versus apoptosis......Page 68
CELLULAR ANTI-APOPTOTIC MECHANISMS......Page 70
Receptor-associated mechanisms......Page 71
FLICE (caspase-8) inhibitory proteins......Page 72
The family of IAPs......Page 73
The Bcl-2 family of proteins......Page 74
Other anti-apoptotic mechanisms......Page 76
NF-kB as an anti-apoptotic transcription factor......Page 77
CONCLUSIONS......Page 79
REFERENCES......Page 80
INTRODUCTION......Page 102
SPHINGOLIPIDS ARE ESSENTIAL FOR CELL VIABILITY AND STRESS RESPONSES IN YEAST AND IN MAMMALIAN CELLS......Page 104
CERAMIDE, THE CARDINAL LIPID OF SPHINGOLIPID METABOLISM......Page 105
Ceramide and cell cycle arrest......Page 106
Ceramide and senescence......Page 107
Ceramide and differentiation......Page 108
Ceramide and the immune response......Page 109
CERAMIDE: A KEY COMPONENT OF INTRACELLULAR STRESS RESPONSE PATHWAYS......Page 110
Ceramide activated protein phosphatase......Page 112
LESSONS FROM YEAST......Page 113
CONCLUSIONS AND FUTURE DIRECTIONS......Page 114
REFERENCES......Page 115
INTRODUCTION......Page 120
RADIATION-INDUCED DNA DAMAGE......Page 121
IMPORTANCE OF PRE-EXISTING PROTEINS......Page 122
PLASMA MEMBRANE INVOLVEMENT IN RADIATION-INDUCED SIGNALLING......Page 123
RESPONSE THROUGH CERAMIDE......Page 124
CELL CYCLE CHECKPOINT ACTIVATION......Page 126
ATAXIA-TELANGIECTASIA......Page 127
REFERENCES......Page 129
Part 2 REGULATION OF APOPTOSIS......Page 139
INTRODUCTION......Page 140
Mechanism Of Activation Of PI3K And Akt......Page 141
Identification of IGF-1 and PDGF as survival factors......Page 142
PI3K mediates cell survival......Page 143
Akt/PKB is the critical PI3K target......Page 144
Organization Of The MAPK Cascade......Page 145
Organization Of The SAPK Cascades......Page 147
Does the balance of MAPK vs SAPK activation determine cell fate?......Page 149
Does MAPK activation promote cell survival?......Page 150
Is SAPK activation required for apoptosis?......Page 151
Caspases and SAPKs, who regulates whom?......Page 152
Summary and speculation......Page 153
REFERENCES......Page 154
5. PROTEIN KINASE C ISOENZYMES: EVIDENCE FOR SELECTIVITY IN THE REGULATION OF APOPTOSIS......Page 165
PKC Isoenzymes......Page 166
Activation of PKC isoenzymes......Page 167
PKC translocation and subcellular targetting......Page 169
PKC ISOENZYMES AND APOPTOSIS......Page 171
PKC-alpha......Page 173
PKC-beta......Page 174
n-PKC Isoenzymes......Page 176
PKC-delta......Page 177
a-PKC Isoenzymes......Page 178
PKC Substrates......Page 179
PKC, APOPTOSIS AND DISEASE......Page 180
CONCLUSIONS......Page 181
REFERENCES......Page 182
INTRODUCTION......Page 192
THE OCCURRENCE OF PCD DURING DEVELOPMENT......Page 193
SIGNALS THAT GOVERN CELL DEATH......Page 194
MUTATIONS THAT REDUCE THE INCIDENCE OF APOPTOSIS......Page 195
THE REAPER REGION, A GENOMIC INTERVAL REQUIRED FOR APOPTOSIS......Page 196
GRIM......Page 199
HEAD INVOLUTION DEFECTIVE......Page 200
GENETICS OF THE H99 CELL DEATH INTERVAL......Page 201
THE DROSOPHILA IAP GENES......Page 202
DROSOPHILA CASPASES......Page 204
FINAL REMARKS......Page 205
REFERENCES......Page 206
Functions Accomplished by Apoptosis......Page 211
VIRAL ANTI-APOPTOTIC GENES......Page 212
p35—A Baculovirus Apoptosis Inhibitory Protein......Page 213
Insect Virus IAP Proteins......Page 214
Protection by IAPs in Evolutionarily Divergent Species......Page 215
Mammalian IAPs......Page 216
Endogenous insect IAPs......Page 217
Structure of Cellular IAPs......Page 218
CONCLUSION......Page 219
REFERENCES......Page 220
INTRODUCTION......Page 225
Cells lacking mitochondria DNA can undergo apoptosis......Page 226
Cell-free system apparently not implying mitochondria......Page 228
A two-step model of apoptosis: an initial mitochondrial step followed by a secondary nuclear step......Page 229
Apoptogenic factors released by mitochondria:cytochrome c and AIF......Page 230
Dissipation of the mitochondrial transmembrane potential......Page 232
Pharmacological data implying mitochondria in apoptosis......Page 233
Impact of Bcl-2 on mitochondria......Page 234
CONCLUSIONS AND PERSPECTIVES......Page 237
REFERENCES......Page 239
INTRODUCTION......Page 246
HOW CAN WE STUDY CELL DEATH COMMITMENT?......Page 247
CASPASES AND THE COMMITMENT TO CELL DEATH......Page 248
CASPASES AND DEVELOPMENTAL CELL DEATH......Page 251
COMMITMENT DOWNSTREAM OF DOWNSTREAM CASPASES......Page 253
ANTI-APOPTOTIC ONCOGENES AND CELL DEATH COMMITMENT......Page 254
WHAT AND WHERE ARE THE COMMITMENT TO CELL DEATH AND APOPTOSIS?......Page 256
REFERENCES......Page 257
Part 3 THE EXECUTION OF APOPTOSIS......Page 265
INTRODUCTION......Page 266
STRUCTURAL FEATURES......Page 267
ACTIVATION DURING APOPTOSIS......Page 269
LINK WITH OTHER COMPONENTS OF THE DEATH PATHWAY......Page 271
FUTURE PERSPECTIVES......Page 273
REFERENCES......Page 274
INTRODUCTION......Page 283
A brief history......Page 284
A predicted structure......Page 286
Insertion into the target membrane lipid bilayer......Page 287
A variety of protease specificities......Page 289
Perforin—undoubtedly the key mediator......Page 290
Granzymes trigger apoptosis......Page 291
Several hypotheses......Page 292
Mammalian Ced-3-like proteases......Page 293
Granzyme B is an exogenous aspase that can activate and augment the caspase cascade......Page 294
Do granzymes have additional intracellular targets?......Page 296
Bcl-2-/CED-9-like inhibitors......Page 297
Viruses Subvert Cell Death Pathways Mediated By Killer Cells......Page 298
Killer Cells Have The Final Say—Or Do They?......Page 299
ACKNOWLEDGEMENTS......Page 300
REFERENCES......Page 302
INTRODUCTION......Page 313
PROTEOLYTIC TARGETS WHICH ARE ACTIVATED AFTER CLEAVAGE......Page 314
SUBSTRATES WHICH ARE INACTIVATED BY CLEAVAGE......Page 316
CYTOSKELETAL PROTEINS......Page 319
PROTEOLYTIC TARGETS INVOLVED IN NEURODEGENERATIVE DISORDERS......Page 322
CONCLUSIONS......Page 323
REFERENCES......Page 326
INDEX......Page 335