Cell Death (Encyclopedia of Life Sciences)

Cover......Page 2
Cell Death......Page 6
Copyright Page......Page 7
Contents......Page 8
Contributors......Page 10
Preface......Page 14
The Siren’s Song: This Death That Makes Life Live......Page 16
Further Reading......Page 27
Introduction......Page 28
From Predator/Prey Coevolution to Symbioses: A ’Red Queen’ Hypothesis in the Bacteria World......Page 29
A Stable Evolutionary Strategy despite High Individual Costs......Page 30
The ’Original Sin’ Hypothesis: Self-destruction as an Unavoidable Consequence of Life......Page 31
Walking Around the Evolutionary Bush......Page 32
’There is Grandeur in This View of Life...’......Page 33
References......Page 34
Further Reading......Page 35
Cell Death in C. elegans......Page 36
ced-3, ced-4, ced-9 and egl-1 are Conserved Genes Essential for Programmed Cell Death in C. elegans......Page 38
Engulfment of Dying Cells......Page 39
DNA Damage-induced Germline Apoptosis......Page 41
Conclusion......Page 42
References......Page 43
Further Reading......Page 44
History and Classification......Page 45
Structure and Active Site......Page 46
Substrate Recognition and Mechanism of Action......Page 47
Inhibitors......Page 48
Caspase Knockouts......Page 49
Pathological Implications......Page 50
References......Page 51
The Apoptosome: The Executioner of Mitochondria-mediated Apoptosis......Page 52
Apaf1......Page 53
Apoptosome assembly......Page 54
Caspase-9......Page 55
Cytochrome c......Page 56
Modulation of the Apoptosome Formation......Page 57
Apoptosome-like Complexes in Evolution. Is the Mitochondrial Pathway of Apoptosis Conserved?......Page 58
Drosophila melanogaster......Page 60
Caspase-9 knockout......Page 62
Final Remarks......Page 63
References......Page 64
Introduction......Page 65
Caspases Classification and Structure......Page 66
Pathways That Lead to Caspase Activation......Page 67
Granzyme B pathway......Page 68
Demolition Phase of Apoptosis......Page 69
Detachment, rounding and blebbing......Page 70
Immune Clearance and Immune Tolerance of Apoptotic Cells......Page 71
References......Page 73
Dismantling the Apoptotic Cell......Page 75
Caspases: Regulators of the Apoptotic Process......Page 76
Effect of caspase-mediated cleavage on target substrates - gain- or loss-of-function......Page 77
Nuclear events......Page 79
Caspases alter the transcriptional and translational machinery......Page 81
Caspase-independent cell death......Page 82
References......Page 83
The BCL-2 Family Proteins - Key Regulators and Effectors of Apoptosis......Page 84
Structure......Page 85
Binding between Family Members......Page 86
Integration and Regulation of Apoptotic Signals......Page 87
Roles In Vivo......Page 88
References......Page 89
BH3-only Proteins......Page 90
Introduction......Page 91
Overview of the apoptotic machinery......Page 92
The role of the Bcl-2 family in tumourigenesis......Page 93
Noxa and Puma......Page 94
Bim/Bod/Bcl2L11......Page 97
Bmf......Page 99
Conclusions......Page 101
References......Page 102
Further Reading......Page 104
Introduction......Page 105
Intrinsic Apoptotic Signalling......Page 106
The Bcl-2 Family Controls MOMP......Page 107
There are Two Models to Explain the Induction of MOMP......Page 108
The Role of Mitochondrial Bioenergetics in MOMP......Page 109
References......Page 110
Further Reading......Page 111
Ultrastructure of mitochondria......Page 112
Dynamic network-like organization of mitochondria in the cell......Page 113
Mitochondrial Fusion......Page 114
Mitochondrial fission......Page 116
Cellular role of Mitochondrial Network Organization: An Overview......Page 117
Role of Bcl-2 Family in the Regulation of Mitochondrial Network Dynamics......Page 118
Role of core mitochondrial fusion and fission proteins in progression of apoptosis......Page 120
References......Page 122
Further Reading......Page 124
Death Ligands and Initiation of Death Receptor Signalling......Page 125
Caspases in Death Receptor Signalling......Page 126
CD95/Fas/APO-1 Signalling......Page 127
Modulation of DR-induced Apoptosis......Page 129
References......Page 130
Further Reading......Page 131
Death Receptors as Potential Therapeutic Targets......Page 132
TRAIL/TRAIL-Receptors - Lessons from Studies at the Molecular Level......Page 134
Targeting TRAIL Death Receptors for Cancer Therapy......Page 139
References......Page 140
Death Receptor-induced Necroptosis......Page 142
Introduction......Page 143
Death Receptor-induced Necroptosis Signalling Complexes......Page 144
Death Receptor-induced Necroptosis, Dying from too much Respiration......Page 146
The Way to Necroptosis is Paved with Many Pathways......Page 148
Physiological Role of Necroptosis......Page 149
References......Page 150
Further Reading......Page 152
Structure of the BIR fold......Page 153
XIAP......Page 156
cIAP1 and cIAP2......Page 157
IAPs and Cancer......Page 158
Survivin and BRUCE......Page 159
References......Page 160
Structures, Domains and Functions in Cell Death (DD, DED, CARD, PYD)......Page 162
Death-inducing signalling complex for activation of caspase-8 and caspase-10 and its inhibition by FLIPs......Page 163
Apoptosome for caspase-9 activation......Page 164
Structures of Isolated Domains and Their Surface Features......Page 165
DED:DED interaction in the tandem DED structure of MC159 v-FLIP......Page 167
Summary......Page 169
References......Page 170
Structure and Function of IAP and Bcl-2 Proteins......Page 171
Introduction......Page 172
Structural Basis of Bcl-2 Family Action......Page 174
Structural Basis of IAP Function......Page 175
Caspase Regulation by IAPs......Page 176
IAP and Bcl-2 Antagonists: A Route to New Cancer Therapies?......Page 177
References......Page 179
Engulfment of Apoptotic Cells and its Physiological Roles......Page 180
‘‘Find-me’’ Signals......Page 181
‘‘Eat-me’’ Signals......Page 182
Signaling Pathways for Engulfment......Page 183
Engulfment Mediated by Bridging Molecules......Page 184
Phosphatidylserine Receptors......Page 186
Conclusions and Future Prospects......Page 187
References......Page 188
Autophagy......Page 190
Two ubiquitin-like conjugations systems......Page 191
Rabs, SNAREs and more......Page 193
Regulation of the Autophagic Pathway......Page 194
Autophagy in Pathological Processes......Page 195
Cancer......Page 196
Infectious and inflammatory diseases......Page 198
Autophagy and Cell Death......Page 199
References......Page 200
Further Reading......Page 203
Regulation of Autophagy......Page 204
Functions of Autophagy......Page 206
Cell Death......Page 207
Neurodegeneration......Page 208
Ageing......Page 209
References......Page 210
Introduction......Page 212
Intrinsic or Bcl-2 blockable apoptosis......Page 213
Extrinsic death receptor apoptosis pathways......Page 214
Death receptor activation of pro-survival signalling......Page 216
Perforin and granzyme B-induced cell death......Page 217
p53......Page 218
Bcl-2......Page 220
XIAP......Page 221
Targeting death receptors in cancer......Page 222
Fas and disease......Page 223
TNF receptor signalling and disease......Page 224
References......Page 225
Further Reading......Page 226
Immune Response to ’Danger’......Page 227
Immunity in Drosophila: the caspase DREDD activates RELISH and is required for resistance to infection by Gram-negative bacteria......Page 228
The Nod signalosome......Page 230
The inflammatory caspases......Page 232
Caspases in Inflammatory Disorders......Page 234
Caspases Tailor the Adaptive Immune Response......Page 235
References......Page 236
Further Reading......Page 237
Introduction......Page 238
Granzyme B and Apoptosis......Page 239
Cell Death Induced by Granzymes Other than Granzyme B......Page 241
References......Page 243
Further Reading......Page 244
Introduction......Page 245
The extrinsic pathway and p53......Page 247
The intrinsic pathway and p53......Page 248
Inhibition of pro-survival signals by p53......Page 249
P53 Family Members and Apoptosis......Page 250
Cancer Therapy and p53......Page 251
References......Page 253
Epidermal Differentiation and Cornified Cell Envelope Formation......Page 255
Skin Transglutaminases......Page 257
Loricrin......Page 260
Small Proline-Rich Proteins......Page 261
Profilaggrin......Page 262
Cell Adhesion and Desquamation......Page 263
Extracellular Proteases......Page 264
Conclusions......Page 265
References......Page 266
Further Reading......Page 267
What happens during apoptosis?......Page 268
Apoptosis mediators......Page 269
Mouse studies of autoimmunity......Page 270
Humans with genetic defects in apoptosis......Page 271
Apoptosis and Malignancy......Page 274
References......Page 275
Further Reading......Page 276
Introduction......Page 277
Generation of ROS/RNS by Casup2+ Influx through NMDA Receptor Channels in Response to Glutamatergic Signalling......Page 278
Nitrosative Stress, Protein Misfolding, Synaptic Injury and Neuronal Cell Death......Page 280
S-nitrosylation of Parkin and the UPS......Page 281
Memantine and derivatives......Page 282
Electrophiles......Page 283
References......Page 285
Introduction......Page 287
Apoptosis Induction and the Benefits of Apoptosis Inhibition for Microbes......Page 288
Inhibitors of Apoptosis Induction: Activation of Pro -survival Pathways......Page 289
Bcl-2-like viral proteins......Page 290
Viral caspase inhibitors: serpin-like proteins and vFLIPs......Page 292
Bacterial Inhibitors of Apoptosis......Page 293
Parasitic Protozoa and the Inhibition of Apoptosis......Page 294
Concluding Remarks......Page 295
References......Page 296
Drug Discovery in Apoptosis......Page 297
Role of Apoptosis in Disease......Page 298
Discovery of Small Molecule Caspase Inhibitors......Page 299
Alternative Approaches to Caspase Inhibitor Discovery......Page 302
Noncaspase Targets for Apoptosis Drug Discovery......Page 304
References......Page 305
Further Reading......Page 306
A
......Page 308
B
......Page 309
C
......Page 310
D
......Page 311
G
......Page 312
K
......Page 313
N
......Page 314
P
......Page 315
S
......Page 316
W
......Page 317
Z
......Page 318