TRAIL (eBook)

Cover 1
Contents 8
Contributors 18
Preface 24
Chapter 1. Specificity of Molecular Recognition Learned from the Crystal Structures of TRAIL and the TRAIL:sDR5 Complex 26
I. Introduction: The TNF and TNF Receptor Superfamilies 27
II. TRAIL and its Receptors 28
III. Selective Antitumor Activity and Biologic Functions of TRAIL 29
IV. Overall Structure of TRAIL 30
V. Zinc Binding and its Critical Role 30
VI. Unique Frame Insertion in the AA'' Loop 33
VII. Structure of TRAIL:sDR5 Complex 34
VIII. Determinants Conferring Specificity of Receptor Recognition 37
IX. Conclusions and Perspectives 38
References 39
Chapter 2. Crystal Structure of RANK Ligand Involved in Bone Metabolism 44
I. Introduction 45
II. The OPG/RANKL/RANK System 46
III. Three-Dimensional Structure of RANKL 50
IV. Conclusion 54
References 55
Chapter 3. Promoter of TRAIL-R2 Gene 60
I. Introduction 61
II. Basic Structure of TRAIL-R2 Promoter 62
III. Regulator of TRAIL-R2 65
IV. Possibility of Cancer Therapy Using TRAIL-R2 68
References 70
Chapter 4. Transcriptional Regulation of the TRAIL-R3 Gene 76
I. Introduction: TRAIL and its Receptors 77
II. Decoy Receptors 79
III. TRAIL-R3 81
IV. Future Directions 85
References 85
Chapter 5. Monoclonal Antibodies Against TRAIL 90
I. Introduction 91
II. Overview of Monoclonal Antibodies Against TRAIL 92
III. Applications of Monoclonal Antibodies Against TRAIL 95
IV. Physiologic Significance of TRAIL 99
V. Future Aspects 101
References 101
Chapter 6. Modulation of TRAIL Signaling Complex 106
I. TRAIL: A New Member of TNF Family 107
II. TRAIL Death Receptors: DR4 and DR5 108
III. TRAIL Decoy Receptors. DcR1, DcR2, and OPG 109
IV. TRAIL-Induced DISC: Cleavage of Apoptosis Initiating Protease Caspase-8 110
V. TRAIL-Induced Bid Cleavage: Activation of Mitochondrial Pathways 112
VI. TRAIL-Induced Cell Proliferation: RIP-Mediated NF-kB Activation 112
VII. TRAIL-Induced c-FLIP Recruitment: DISC Modulation 113
VIII. TRAIL-Induced PED Recruitment: Differential Modulation of the DISC 115
IX. TRAIL Physiologic Functions: Tumor Surveillance 116
X. Recombinant TRAIL: A Novel Cancer Therapeutic Agent 116
References 118
Chapter 7. TRAIL and NF kB Signaling„A Complex Relationship 126
I. Introduction 127
II. Regulation of TRAIL-Induced Apoptosis by NFkB 138
III. TRAIL Activates NFkB 144
References 146
Chapter 8. CARDINAL Roles in Apoptosis and NFkB Activation 158
I. Introduction 159
II. Regulation of NFkB Activation 159
III. CARD Proteins 160
IV. CARD Proteins and NFkB Activation 160
V. Functions of CARDINAL 163
VI. CARDINAL as a Negative Regulator of Diverse NFkB Activation Pathways 163
VII. CARDINAL and Apoptosis 165
VIII. CARDINAL and Caspase-1 Activation 165
IX. The Inflammasome 166
X. CARDINAL Contradictions 167
XI. Conclusions 168
References 168
Chapter 9. TRAIL in the Airways 174
I. Introduction 175
II. TRAIL: Synthetic and Signaling Pathways 175
III. Effects of TRAIL in the Airways 178
IV. Conclusions 187
References 187
Chapter 10. TRAIL Death Receptors, Bcl-2 Protein Family, and Endoplasmic Reticulum Calcium Pool 194
I. Introduction 195
II. The Endoplasmic Reticulum 195
III. Endoplasmic Reticulum CA2+ Pools and Regulation of Apoptosis 197
IV. Concluding Remarks 208
References 210
Chapter 11. FLIP Protein and TRAIL-Induced Apoptosis 214
I. Introduction 215
II. FLIP: Structure and Mechanisms of Action 215
III. FLIP Function in Normal Physiology and Disease 219
IV. TRAIL and FLIP 222
References 224
Chapter 12. Epidermal Growth Factor and TRAIL Interactions in Epithelial-Derived Cells 232
I. Epidermal Growth Factor Receptor–Mediated Cell Survival 233
II. Epidermal Growth Factor Signaling Pathways 234
III. Transcriptional Activation 238
IV. Antiapoptotic Proteins 239
V. Targeting Epidermal Growth Factor Receptor Signaling for Treatment of Cancer 241
VI. TRAIL Death Receptors 242
VII. TRAIL as a Cancer Treatment 243
VIII. Convergence of the Epidermal Growth Factor and TRAIL Signaling Pathways 244
References 247
Chapter 13. TRAIL and Ceramide 254
I. Introduction 255
II. TRAIL 256
III. Sphingolipids 259
IV. TRAIL and Ceramide 268
References 269
Chapter 14. TRAIL and Viral Infection 282
I. Introduction 283
II. Apoptosis as a Process of Degradation of Host Cell and Viral Constituents 284
III. Death Receptor/Ligand Systems 285
IV. The Cytotoxic Activity of TRAIL Against Virus-Infected Cells 287
V. Viral Strategies to Circumvent TRAIL-Induced Apoptosis 289
VI. TRAIL in Virus-Induced Immunosuppression 290
VII. Viruses and TRAIL in Malignant Disease 291
VIII. Conclusions 293
References 294
Chapter 15. Modulation of TRAIL Signaling for Cancer Therapy 300
I. Introduction 301
II. The Core Apoptotic Machinery 302
III. TRAIL and its Receptors 303
IV. TRAIL Signaling 303
V. Defective TRAIL Signaling in Cancers 304
VI. TRAIL and Cancer Therapy 306
VII. Conclusions 309
References 310
Chapter 16. Interferon-Gamma and TRAIL in Human Breast Tumor Cells 316
I. Introduction 317
II. Interferon-y 318
III. TRAIL System 322
IV. Regulation by IFN-y of TRAIL-Induced Apoptosis in Breast Tumor Cells 328
V. Conclusions 333
References 334
Chapter 17. Retinoids and TRAIL: Two Cooperating Actors to Fight Against Cancer 344
I. Introduction 345
II. Origin of Retinoids 347
III. Mechanism of Retinoid Action 347
IV. Anticancer Activity of Retinoic Acids 350
V. Retinoid Action on Human Cancers 353
VI. APO2L/TRAIL and its Receptors 355
VII. Preventive and Therapeutic Potential of Retinoids: The TRAIL Connection 359
VIII. Future Directions 361
References 363
Chapter 18. Potential for TRAIL as a Therapeutic Agent in Ovarian Cancer 372
I. Introduction 373
II. Ovarian Cancer 373
III. Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand 376
IV. Interleukin-8 379
V. Role of p38 MAPK in Apoptosis 381
VI. Summary 382
References 383
Chapter 19. TRAIL and Chemotherapeutic Drugs in Cancer Therapy 390
I. Introduction 391
II. Receptors for TRAIL 392
III. Signaling Pathways of TRAIL Receptors 393
IV. Bioactivity of TRAIL 394
V. Synergistic Effect of TRAIL and Chemotherapeutic Drugs 397
VI. Molecular Mechanisms of the Synergistic Effect 397
VII. Conclusions and Prospects 401
References 402
Chapter 20. Additive Effects of TRAIL and Paclitaxel on Cancer Cells: Implications for Advances in Cancer Therapy 410
I. Introduction 411
II. Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand 413
III. Paclitaxel 417
IV. Biologic and Clinical Benefits of TRAIL and Paclitaxel Combination Therapy 422
V. Conclusions 427
References 428
Chapter 21. Regulation of Sensitivity to TRAIL by the PTEN Tumor Suppressor 434
I. Introduction 436
II. Regulation of TRAIL-Induced Apoptosis 436
III. Regulation of the Phosphatidylinositol-3 Kinase Pathway by PTEN 439
IV. Modulation of TRAIL Sensitivity by the Phosphatidylinositol-3 Kinase/PTEN/Akt Pathway 441
V. Downstream Targets of the Phosphatidylinositol-3 Kinase/PTEN/Akt Pathway 442
VI. Strategies for Overcoming TRAIL Resistance 444
VII. Conclusion 446
References 447
Chapter 22. TRAIL and Malignant Glioma 452
I. Malignant Glioma 453
II. Apoptosis in Cancer 455
III. Apoptosis Pathways Overview 458
IV. TRAIL 460
V. TRAIL and Glioma 462
VI. Future Directions 469
References 469
Chapter 23. Regulation of TRAIL-Induced Apoptosis by Ectopic Expression of Antiapoptotic Factors 478
I. Introduction 479
II. Negative Regulation of TRAIL-Induced Apoptosis 483
III. Inhibitors of Antiapoptotic Factors as Therapeutic Agents 496
IV. Effect of TRAIL on Normal Cells 498
V. Conclusions 499
References 500
Index 510