Apoptosis

by Kumar, Sharad

• ISBN13: 9783540646242
• ISBN10: 3540646248
• Format: Hardcover
• Copyright: 1999-01-01
• Publisher: Springer Verlag

Summary

This volume deals with many of the recent advances made in uncovering the molecular and cellular basis of apoptosis and elaborates on how this accumulating knowledge is helping us to understand the significance of apoptosis in pathogenesis of diseases arising from inappropriate cell death. Further, mechanistic aspects of cell death and role of apoptosis in disease is covered.

Table of Contents

Caspases in Cell Death	1	(24)
L. Dorstyn
M. Kinoshita
S. Kumar
1 Introduction	1	(1)
2 Discovery of Caspases	1	(1)
3 Structure	2	(2)
4 Substrate and Target Specificities	4	(2)
5 Caspases in Apoptosis	6	(5)
5.1 Viral Inhibitors of Caspases	6	(2)
5.2 Synthetic Inhibitors of Caspases Suppress Apoptosis	8	(2)
5.3 Caspase Null Mutant Mice	10	(1)
5.4 Activation of DNA Fragmentation Factor	10	(1)
6 Regulation	11	(5)
6.1 Regulation by Transcription	11	(1)
6.2 Regulation by Proteolytic Activation	12	(1)
6.3 Regulation by Alternative Splicing	12	(1)
6.4 Regulation by Subcellular Localisation	13	(1)
6.5 Regulation by Cellular Proteins	14	(2)
6.5.1 Apoptosis Inducing Factor	14	(1)
6.5.2 Cytochrome c	14	(1)
6.5.3 Apaf-1	15	(1)
6.5.4 Cellular FLIPs	15	(1)
6.5.5 Mammalian IAP-Like Proteins	16	(1)
7 Non-apoptotic Functions	16	(1)
8 Concluding Remarks	17	(1)
References	17	(8)
Proteolytic Targets in Cell Death	25	(20)
D. Watters
N. Waterhouse
1 Introduction	25	(1)
2 Proteolytic Targets Involved in Cell Homeostasis	26	(6)
2.1 DNA Repair and Replication	26	(2)
2.1.1 Poly (ADP-Ribose) Polymerase	26	(1)
2.1.2 DNA-Dependent Protein Kinase	26	(1)
2.1.3 Replication Factor C	27	(1)
2.1.4 Topoisomerases and Histones	27	(1)
2.2 RNA Processing	28	(1)
2.2.1 The 70-kDa Protein Component of the U1 Small Ribonucleoprotein	28	(1)
2.2.2 Heteronuclear Ribonucleoprotein C	28	(1)
2.3 Components of Signal Transduction Pathways	29	(3)
2.3.1 DNA Fragmentation Factor	29	(1)
2.3.2 Phospholipase A2	29	(1)
2.3.3 Protein Kinase CDelta	30	(1)
2.3.4 PITSLRE Kinases	30	(1)
2.3.5 Retinoblastoma Protein	30	(1)
2.3.6 Mdm2	31	(1)
2.3.7 Sterol Regulatory Element Binding Proteins	31	(1)
3 Proteins Involved in Maintenance of Cell Structure	32	(4)
3.1 Cytoskeletal Proteins	32	(2)
3.1.1 Nuclear Lamins	32	(1)
3.1.2 Nuclear Matrix Protein	32	(1)
3.1.3 Fodrin	33	(1)
3.1.4 Actin	33	(1)
3.2 Regulators of the Cytoskeleton	34	(2)
3.2.1 p21-Activated Kinase 2	34	(1)
3.2.2 Gas2	35	(1)
3.2.3 D4-GDP Dissociated Inhibitor	35	(1)
4 Proteolytic Targets of Unknown Function	36	(1)
4.1 Huntingtin	36	(1)
4.2 Adenomatous Polyposis Coli	36	(1)
4.3 Terminin	37	(1)
5 Molecular Ordering of Proteolytic Events	37	(1)
6 Conclusions	38	(1)
References	39	(6)
The Point of No Return: Mitochondria, Caspases, and the Commitment to Cell Death	45	(18)
D.R. Green
G.P. Amarante-Mendes
1 Introduction: The Problem of Time of Death	45	(1)
2 The Faces of Cell Death	46	(1)
3 "Commitment" to Die	47	(1)
4 Caspases and the Moment of Truth	47	(3)
5 Programmed Cell Death: Caspases as Either Judge of Executioner	50	(1)
6 When the Executioner is Also the Judge	51	(3)
7 Anti-apoptotic Oncogenes and Refusal to Commit	54	(1)
8 What and Where is Commitment?	54	(3)
9 Summary	57	(1)
References	58	(5)
Serpins and Regulation of Cell Death	63	(28)
P.I. Bird
1 The Serpin Superfamily	63	(5)
1.1 Evolution and Roles of Serpins	63	(1)
1.2 Serpin Structure	64	(2)
1.3 Mechanism of Serpin Inhibition of Cognate Proteinases	66	(1)
1.4 Specificity of the Serpin-Proteinase Interaction	67	(1)
1.5 Ovalbumin Serpins	67	(1)
2 Serpins and Apoptosis	68	(14)
2.1 Poxvirus Cytokine Response Modifier A (CrmA/SPI-2)	69	(8)
2.1.1 Structure and Function of CrmA	69	(1)
2.1.2 Inhibition of Caspases by CrmA	69	(1)
2.1.2.1 Caspase-1	69	(1)
2.1.2.2 Caspase-3	70	(1)
2.1.3 Interaction of CrmA with Granzyme B	70	(1)
2.1.4 CrmA and the Control of Apoptosis	71	(1)
2.1.4.1 CrmA in Matrix Detachment, Serum and Growth Factor Withdrawal	71	(1)
2.1.4.2 CrmA in FasL- and TNF-Induced Apoptosis	72	(2)
2.1.4.3 CrmA and Staurosporine, Steroid Hormone and Radiation-Induced Apoptosis	74	(1)
2.1.4.4 Role of CrmA in Cytotoxic Lymphocyte-Induced Apoptosis	75	(1)
2.1.4.5 Role of CrmA During Viral Infection	76	(1)
2.2 Poxvirus Serine Protease Inhibitor 1 (SPI-1)	77	(1)
2.3 Proteinase Inhibitor 9 (PI-9)	78	(1)
2.4 Plasminogen Activator Inhibitor 2 (PAI-2)	79	(2)
2.5 Protease Nexin I (PN-I)	81	(1)
3 Summary	82	(1)
References	83	(8)
The IAP Family of Apoptotic Regulators	91	(14)
L.J. Eiben
C.S. Duckett
1 Introduction	91	(2)
1.1 Apoptosis: An Essential, Evolutionary Conserved Biological Phenomenon	91	(1)
1.2 Dynamic Interplay Between Viruses and Host Cells	92	(1)
2 Discovery of Baculoviral iap Genes	93	(1)
3 Structure of IAP Proteins	94	(1)
4 Discovery of Cellular iap Homologues	95	(1)
5 Vertebrate IAP-Related Proteins	95	(3)
5.1 c-IAP1 and c-IAP2	95	(2)
5.2 Human IAP-Like Protein (hILP)	97	(1)
5.3 Neuronal Apoptosis Inhibitory Protein (NAIP)	97	(1)
5.4 Survivin	97	(1)
6 Invertebrate IAP-Related Proteins	98	(1)
7 Mechanism of Action of IAP Proteins	98	(3)
7.1 Invertebrate IAPs	98	(1)
7.2 Vertebrate IAPs	99	(2)
8 Future Directions	101	(1)
References	102	(3)
Apoptosis Versus Necrosis: The Shape of Neuronal Cell Death	105	(32)
M. Leist
P. Nicotera
1 Introduction	105	(1)
2 Significance of Neuronal Apoptosis	105	(4)
3 Specific Features of Cell Death in the Nervous System	109	(2)
4 Excitotoxicity and Nitric Oxide in Neuronal Death	111	(9)
4.1 Excitotoxicity	111	(1)
4.2 Energy-Linked Excitotoxicity	112	(1)
4.3 Nitric Oxide	113	(3)
4.4 The Role of Poly-(ADP-Ribose)-Polymerase	116	(1)
4.5 The Role of Apoptosis in Excitotoxicity	116	(4)
5 Apoptosis in Neuronal Disease and Development	120	(2)
5.1 Neuronal Apoptosis	120	(1)
5.2 Oligodendrocyte Apoptosis	121	(1)
References	122	(15)
Prevention of Neuronal Cell Death by Bcl-2	137	(20)
Y. Tsujimoto
1 Introduction	137	(1)
2 The bcl-2 Gene Family	137	(4)
2.1 Discovery of the bcl-2 Gene	137	(1)
2.2 Discovery of the Anti-apoptotic Activity of Bcl-2	138	(1)
2.3 Bcl-2 Family Proteins	138	(2)
2.4 Bcl-2-Binding Proteins	140	(1)
3 Role of Bcl-2 in Neurons	141	(6)
3.1 Expression in Embryos Versus Adults	141	(1)
3.2 Lessons from bcl-2-Transgenic Mice with Gain-of-Function or Loss-of-Function	142	(5)
3.2.1 Prevention of Naturally Occurring Cell Death and Injury-Induced Cell Death by Bcl-2 Overexpression	142	(1)
3.2.2 Bcl-2 is Not a Permissive Factor for Neutrotrophic Factor-Derived Survival Signals	143	(1)
3.2.3 Bax is Required for Trophic Factor Depletion-Induced Neuronal Death and Developmental NOCD of Sympathetic and Facial Motor Neurons	144	(1)
3.2.4 Dominant Role of Bcl-2 in Maintenance of Several Neuron Populations in the Early Postnatal Period	145	(1)
3.2.5 Enhancement of Axonal Regeneration by Bcl-2	146	(1)
3.2.6 Failure of Bcl-2 Overexpression to Prevent Motoneuron Degeneration in Wobbler and Progressive Motor Neuropathy Mutant Mice	146	(1)
4 Biochemical Basis for Prevention of Cell Death by Bcl-2	147	(1)
5 Role of Bcl-2 Family Proteins in Human Neuronal Diseases	148	(2)
5.1 Ischemic Injury	148	(1)
5.2 Spinal Muscular Atrophy (SMA)	149	(1)
6 Implications	150	(1)
References	150	(7)
CD95 (APO-1/Fas) in Hematopoietic Diseases	157	(18)
K.-M. Debatin
1 Introduction	157	(1)
2 CD95 Mediated Death	158	(1)
3 Genetic Defects of CD95 in Lymphoproliferative Disorders	159	(2)
4 CD95 and Hematologic Malignancies	161	(2)
5 Role of the CD95 System in T Cell Depletion in AIDS	163	(2)
6 The CD95 System and Anticancer Drugs	165	(2)
7 Conclusion	167	(1)
References	167	(8)
The Cornified Envelope: A Model of Cell Death in the Skin	175	(38)
G. Melino
V. De Laurenzi
M.V. Catani
A. Terrinoni
B. Ciani
E. Candi
L. Morekov
P.M. Steinert
1 Introduction	175	(1)
2 The Cornified Cell Envelope	176	(1)
3 Transglutaminases	177	(4)
3.1 Defects of TGases	180	(1)
4 Involvement of TGase 2 in Apoptosis	181	(3)
5 Modulation of TGases by Retinoids	184	(2)
6 TGase Substrates of Epidermal Cornified Cell Envelopes	186	(14)
6.1 Loricrin	186	(5)
6.2 Small Proline-Rich Proteins (SPRs)	191	(2)
6.3 Trichohyalin	193	(2)
6.4 Involucrin	195	(1)
6.5 Profilaggrin	195	(2)
6.6 Keratin Intermediate Filaments	197	(3)
7 Diseases Caused by Defects in CE Structure	200	(4)
7.1 CE Structural Proteins	200	(2)
7.2 Keratin Diseases	202	(1)
8 Skin Lipids and Their Defects	203	(1)
9 Cell Death: Apoptosis (Basal Layer) Versus Cornification (Cornified Layer)	204	(1)
10 Conclusions: Has Cornification-Cell Death Evolved from Apoptosis?	205	(1)
References	206	(7)
Radiation-Induced Cell Death and its Implications in Human Disease	213	(20)
M.F. Lavin
1 Introduction	213	(1)
2 Radiation-Induced DNA Damage	214	(1)
3 Extranuclear Targets for Radiation Damage/Signalling	215	(1)
4 Reactive Oxygen Species and Signalling	216	(2)
5 p53 and Radiation-Induced Cell Cycle Delay	218	(1)
6 p53 and Radiation-Induced Apoptosis	219	(2)
7 Radiation-Induced Ceramide Production and Apoptosis	221	(2)
8 Apoptosis/Radiation and Disease	223	(2)
References	225	(8)
T Cell Apoptosis in HIV Infection: Mechanism and Relevance for AIDS Pathogenesis	233	(16)
M.-L. Gougeon
E. Ledru
H. Lecoeur
S. Garcia
1 Introduction	233	(1)
2 Programmed Cell Death (PCD) Involvement in CD4 T Cell Depletion in AIDS	234	(2)
2.1 Increased Lymphocyte Apoptosis in HIV-Infected Patients	234	(1)
2.2 Priming for Apoptosis is the Consequence of Chronic Immune Activation	235	(1)
2.3 Relation Between Lymphocyte Apoptosis and Disease Progression	236	(1)
3 Molecular Control of PCD in HIV Infection: Role of the Fas/FasL System	236	(4)
3.1 Dysregulation of the Fas (CD95) System in HIV Infection	236	(2)
3.2 Effectors of Fas-Mediated Apoptosis	238	(1)
3.3 Molecular Control of the Fas Pathway in HIV Infection	239	(1)
4 Cytokine Dysregulation in HIV Infection: Consequences on T Cell Susceptibility to Apoptosis	240	(2)
4.1 The Th1/Th2 Dichotomy in HIV Infection	240	(1)
4.2 Influence of Cytokines on T Cell Apoptosis	241	(1)
5 Consequences of Exacerbation of PCD on T Cell Homeostasis in HIV Infection	242	(2)
5.1 Control of T Cell Homeostasis by Apoptosis	242	(1)
5.2 Altered Homeostasis and Renewal Capacities in HIV -Infected Patients	243	(1)
References	244	(5)
Index	249