In apoptosis in the mammalian system, cells have a finite life - they develop, are used and then die. Cancer cells escape this programmed routine but, from an understanding of apoptosis, they can be programmed to die. This book addresses the
Author(s): M Sluyser
Edition: 1
Year: 1996
Language: English
Pages: 303
Book Cover......Page 1
Half-Title......Page 2
Title......Page 3
Copyright......Page 4
Contents......Page 5
Editor’s Introduction......Page 7
1.1 Introduction......Page 8
1.3 Genesis of the Apoptosis Concept......Page 9
1.4 Morphological Features of Apoptosis......Page 12
1.5 Further Development of the Apoptosis Concept, 1972–1980......Page 14
1.6 Applications and Mechanisms 1981–1990......Page 18
1.7 Apoptosis—a Scientific Revolution......Page 20
References......Page 21
2.1 Introduction......Page 25
2.2 Proteases......Page 26
2.3 Nucleases......Page 28
2.5 Lipid Modifying Enzymes......Page 32
2.6 Transglutaminases......Page 33
References......Page 34
3.1 Introduction......Page 41
3.2 Characteristics of Apoptosis......Page 42
3.3 Molecular Mechanisms of Apoptosis......Page 44
3.3.2 Determination of Apoptosis......Page 47
3.3.3 Execution of Apoptosis......Page 49
3.4 Biological Implications of Apoptosis......Page 54
3.5 Conclusion......Page 56
References......Page 57
4.2 Genetic Regulation of Apoptosis......Page 61
4.3 Genes Associated with Apoptosis......Page 62
4.5 Apoptosis Transduced from the Cell Surface......Page 63
4.6 Cell Death Genes in Invertebrates and Mammalian Homologues......Page 64
4.7 Oncogenes Associated with Apoptosis......Page 65
References......Page 66
5.2 Models of Programmed Cell Death......Page 70
5.2.1 Invertebrate Models of Programmed Cell Death......Page 71
c-Myc and Apoptosis......Page 73
Bcl-2: a Suppressor of Apoptosis......Page 76
Expression of Immediately Early Genes in Apoptosis......Page 77
Tumour Suppressor Genes and their Role in Apoptosis......Page 78
5.3.1 Anti-apoptotic Insect Virus Genes......Page 79
5.3.2 Anti-apoptotic Genes in Mammalian Viruses......Page 80
5.5 ‘Death’ Genes......Page 82
5.6 Summary—Apoptosis and the Possibilities for Novel Pharmacological Intervention in Disease......Page 83
Interactions Between Genes that Regulate Apoptosis and their Relevance to Tumourigenesis......Page 84
References......Page 85
6.1 Introduction......Page 93
6.2.2 Biochemical and Biological Properties of p53......Page 94
6.3 p53 can Promote Apoptosis......Page 95
6.4.1 Apoptosis in Immature Thymocytes......Page 96
6.4.3 Apoptosis in Epithelial Stem Cells......Page 97
6.4.5 Mechanism of Apoptosis......Page 98
6.4.6 p53-Dependent Apoptosis and Tumor Suppression......Page 99
6.5.1 Apoptosis is a Common Feature of Malignant Tumors......Page 100
p53 is Required for E1A-induced Apoptosis......Page 101
Many Oncogenic Alterations Modulate p53-dependent Apoptosis......Page 102
6.5.3 p53 can Directly Suppress Oncogenic Transformation......Page 103
Proliferation and Apoptosis in the Mouse Embryonic Lens......Page 104
p53 Mutations in Anaplastic Wilm’s Tumor......Page 105
6.6.1 Model Systems......Page 106
6.6.2 Does p53 Mutation Enhance Drug Resistance in Human Cancer?......Page 108
6.7 Mechanism of p53-dependent Apoptosis in Oncogene-expressing Cells......Page 109
6.7.2 Physiological Stimuli and Genotoxic Agents Trigger Apoptosis......Page 110
6.7.4 Biochemical Activities of p53 Involved in Apoptosis......Page 111
References......Page 112
7.2 Discovery of Bcl-2 at the Breakpoints of t(14;18) Translocations in Lymphomas......Page 119
7.2.1 Structure and Consequences of t(14;18) Translocations in Follicular Lymphomas......Page 120
7.3 Bcl-2 Gene Activation in Other Types of Cancer......Page 123
7.3.1 Loss of p53 Tumor Suppressor as a Potential Mechanism of bcl-2 Deregulation......Page 124
7.4 Bcl-2 and Chemoresistance in Cancer......Page 125
7.4.1 Bcl-2 Blocks both p53-dependent and p53-independent Pathways for Drug-induced Apoptosis......Page 127
7.5 Bcl-2 Regulates a Distal Event in an Evolutionarily Conserved Pathway for Cell Death......Page 128
7.6 The Bcl-2 Protein: Possible Mechanisms of Action......Page 130
7.7.1 Bcl-2 Homologs......Page 132
BAG-1......Page 138
R-Ras and Raf-1......Page 139
Nip-1, Nip-2, Nip-3......Page 140
7.8 Expression of Bcl-2 Family Proteins in Normal Tissues and Cancers......Page 141
7.8.1 Molecular Mechanisms of Bcl-2 Gene Regulation......Page 142
7.8.2 Tumor Suppressor p53 is a Direct Transcriptional Regulator of bax Gene Expression......Page 143
References......Page 146
8.1 Introduction......Page 158
8.2 Detection and Occurrence of PCD During Development......Page 159
8.4 Signals that Govern Cell Death......Page 160
8.5 Mutations that Cause Ectopic Cell Death......Page 161
8.6 Mutations and Genes that Reduce the Incidence of Apoptosis......Page 162
8.7 Reaper, a Gene Required for Apoptosis......Page 163
8.8 Other Candidate Cell Death Genes Drosophila......Page 165
8.9 Engulfment of Apoptotic Cells......Page 166
8.10 Conclusion......Page 167
References......Page 168
9.2 Observations of Cell Death in Different Organisms......Page 173
9.3 Natural Selection of Genes for Cell Death......Page 174
9.4 The Mechanism of Cell Death......Page 175
9.5 Uses for Cell Death......Page 177
9.6 Apoptosis and Necrosis......Page 178
9.8 The Role of Cytotoxic Cells......Page 179
References......Page 180
10.1 Introduction......Page 184
10.3 Occurrence and Localization of Apoptosis in the Gonads......Page 185
10.4 Hormonal Control of Gonadal Cell Apoptosis......Page 187
10.4.1 Role of Gonadotropins......Page 188
10.4.2 Role of Sex Steroids......Page 189
10.4.3 Role of Growth Factors......Page 191
10.4.4 Role of Other Factors......Page 192
10.5 Comparison of Ovarian and Testicular Cell Apoptosis......Page 194
10.6 Conclusion......Page 195
References......Page 196
11.2.1 Development of T Lymphocytes in the Thymus......Page 203
11.2.2 Development of B Lymphocytes in the Bone Marrow......Page 208
11.2.3 B-1 B Cells......Page 210
11.3.1 Antigen-induced Apoptosis of Mature T Cells......Page 211
11.3.2 Affinity Maturation of T-dependent B Cell Responses......Page 212
11.3.3 Fas and its Counterstructure......Page 214
11.4.1 Mode of Target Cell Destruction: the Role of Perforin......Page 216
11.5 The Innate Immune System......Page 217
11.5.2 Phagocytosis of Apoptotic Cells......Page 218
11.6 Conclusions: Apoptosis and the Immune System in Health and Disease......Page 220
References......Page 222
12.1 Introduction......Page 230
12.2.1 Apoptosis of CS-21 Cells in vitro......Page 231
12.2.2 Suppression of Apoptosis by Adhesion to Stromal Cells......Page 232
12.3.2 Inhibition of Apoptosis by mAbs......Page 235
12.4 Summary......Page 236
References......Page 238
13.1 Introduction......Page 241
Epithelia......Page 242
Epithelia......Page 243
13.2.4 Relationship Between bcl-2 and p53 Expression in Normal Tissues......Page 244
13.3.1 Haematopoietic Malignancies......Page 245
13.3.3 Prostate and bcl-2......Page 247
Acknowledgements......Page 248
References......Page 249
14.1 Introduction......Page 252
14.2 Neural Trophic Factors and their Receptors......Page 253
14.3 The Role of the ICE Family of Genes in Controlling Neuronal Cell Death......Page 256
14.4 The Role of bcl-2 in Neuronal Cell Death......Page 258
14.5.1 Alzheimer’s Disease......Page 259
14.5.3 Ischemia......Page 261
14.5.4 Superoxide Dismutase and Motoneuron Disease (ALS)......Page 262
References......Page 263
Index......Page 271
