Hetz BCL-2 Protein Family

Essential Regulators of Cell Death
1. Auflage 2011
ISBN: 978-1-4419-6706-0
Verlag: Springer
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 145 Seiten

In this book, scientists pioneering the field have compiled a series of focused chapters to highlight the relevance of the BCL-2 family of proteins in apoptosis, physiology and disease. An important focus of this volume is considering the potential TH ERA PEUT IC benefits of targeting apoptosis pathways in the context of human disease. Readers interested in understanding how a cell handles stress and the consequences of dysregulation of this process for human disease will find this book very valuable. It attempts to describe a fascinating area of research where physiology and biomedicine converge at different levels, revealing a trip from the molecular regulation of apoptosis to the impact of this process to the physiology of a whole organism.

Claudio Hetz received his BA in Biotechnology Engineering from the University of Chile in 2000. In his PhD work with Claudio Soto at Serono Pharmaceutical Research Institute, Geneva, he showed that Prion pathogenesis involves endoplasmic reticulum stress responses and apoptosis. In 2004 he joined as a postdoctoral fellow Stanley Korsmeyer's lab at Dana-Farber Cancer Institute, a pioneer in the apoptosis field. Together they discovered new functions of the BCL-2 family in organelle physiology. Dr. Hetz followed his projects in Laurie Glimcher's lab at Harvard. During this period he expanded his studies on neurodegeneration, addressing the connection between apoptosis and the unfolded protein response in vivo. Since 2007 he is an Assistant Professor at the University of Chile and adjunct professor at Harvard. His lab uses animal models to investigate the signaling responses involved in protein misfolding disorders and the role of the BCL-2 protein family in stress conditions. He was recently awarded with the TWAS-ROLAC Young Scientist Prize, also as finalist with the Eppendorf and Science Award in Neurobiology, and other important recognitions.

Autoren/Hrsg.

Hetz, Claudio

Inhaltsverzeichnis

1;Title Page;3
2;Copyright Page;4
3;FOREWORD;5
4;PREFACE;6
5;ABOUT THE EDITOR...;8
6;PARTICIPANTS;9
7;Table of Contents;12
8;Chapter 1 Homeostatic Functions of BCL-2 Proteins beyond Apoptosis;15
8.1;Introduction;15
8.2;Mitochondrial Energy Metabolism;17
8.2.1;Functional Interaction of BCL-XL and VDAC in Regulation of Mitochondrial Outer Membrane Permeability to Metabolites;18
8.2.2;Deciphering Calcium Signals: BCL-2 Family and the ER-Mitochondria Cross Talk;19
8.2.3;Remodeling the Mitochondrial Membrane: BCL-2 Family Members and Mitochondrial Dynamics;21
8.2.4;BCL-2 Family and Mitochondrial Fuel Metabolism: A Role for BAD in Glucose Sensing;24
8.3;Autophagy;28
8.4;Protein Quality Control and the Unfolded Protein Response;30
8.4.1;The Sensors and Effectors Downstream of UPR;31
8.4.2;The Outcomes of Signaling Downstream of UPR;31
8.5;Physiologic Roles for BCL-2 Family Proteins in Cell Cycle Checkpoints, Differentiation and DNA Damage Response;33
8.5.1;BCL-2 Family and Cell Cycle Checkpoints;33
8.5.2;Differentiation;35
8.5.3;has not been formally examined.;36
8.6;Conclusion;37
8.7;References;37
9;Chapter 2 Alternative Functions of the BCL-2 Protein Family at the Endoplasmic Reticulum;47
9.1;Introduction;47
9.2;The BCL-2 Protein Family and the Unfolded Protein Response;48
9.3;Chronic ER Stress and BH3-Only Proteins;51
9.4;The BCL-2 Protein Family and the Calcium Rheostat;53
9.5;Autophagy and the BCL-2 Protein Family of Proteins;54
9.5.1;The BCL-2 Protein Family and ER Morphogenesis;56
9.6;Conclusion;56
9.7;References;57
10;Chapter 3 BH3-Only Proteins and Their Effects on Cancer;62
10.1;Introduction;62
10.2;Categories of BCL-2 Family Proteins and Their Apoptotic Functions;63
10.2.1;Multidomain Proapoptotic Members;63
10.2.2;Anti-Apoptotic BCL-2 Family Members;64
10.2.3;Proapoptotic BH3-Only Function;64
10.3;Regulation of Various BH3-Only Proteins and Cell Stress Sensing;66
10.4;BH3-Only Proteins and Cancer Development;68
10.5;BH3-Only Proteins and Chemotherapy Response and Resistance;70
10.6;BH3-Only Mimetic Drugs;71
10.7;Conclusion;71
10.8;References;71
11;Chapter 4 Endoplasmic Reticulum Stress and BCL-2 Family Members;77
11.1;Introduction;77
11.2;UPR: The Good and the Evil Side;79
11.3;UPR and BCL-2 Family Members;80
11.4;Autophagy, UPR and BCL-2 Family Members;83
11.5;Conclusion;85
11.6;References;86
12;Chapter 5 Targeting Survival Pathways in Lymphoma;90
12.1;Introduction;90
12.1.1;BCL-2 Proteins and Apoptosis;91
12.2;Pharmacologic Modulation of BCL-2 Proteins and Apoptosis;92
12.2.1;Modified Peptides;93
12.2.2;Small Molecule Inhibitors of Anti-Apoptotic Proteins;93
12.2.2.1;HA14-1 and Analogs;93
12.2.2.2;BH3I-2 and Analogs;94
12.2.2.3;Antimycin and Analogs;95
12.2.2.4;Gossypol and Derivatives;95
12.2.2.5;GX015-070 (Obatoclax Mesylate);97
12.2.2.6;ABT-737 and ABT-263;98
12.2.3;Antisense Strategies;100
12.2.4;Targeting TRAIL;101
12.2.4.1;Agonistic Antibodies;101
12.2.4.2;Ligand Based Receptor Agonism;101
12.3;BCL-2 Proteins and Non-Apoptotic Cell Death;101
12.4;Conclusion;102
12.5;References;102
13;Chapter 6 The Interplay between BCL-2 Family Proteins and Mitochondrial Morphology in the Regulation of Apoptosis;108
13.1;Introduction;108
13.1.1;An Historical Perspective on the Proteins of the BCL-2 Family;108
13.1.2;Apoptotic Pathways;109
13.2;BCL-2 Family;109
13.2.1;BH Domains and Molecular Interaction;111
13.2.2;BCL-2 Antiapoptotic Proteins;111
13.2.2.1;BCL-2 and BCL-XL;111
13.2.2.2;Bcl-W;112
13.2.2.3;Mcl-1;113
13.2.2.4;Bfl-1/A1;113
13.2.3;BCL-2 Proapoptotic Proteins;114
13.2.3.1;Bax and Bak;114
13.2.4;BH3 Only Proteins;114
13.3;Mitochondrial Shape and Apoptosis;117
13.3.1;Mitochondrial Morphology: An Equilibrium between Fusion and Fission;117
13.3.2;Mitochondrial Fragmentation during Apoptosis: The Role of BCL-2 Family Members;119
13.3.3;Mitochondrial Ultrastructural Changes during Apoptosis;120
13.4;Conclusion;120
13.5;References;120
14;Chapter 7 Noncanonical Functions of BCL-2 Proteins in the Nervous System;126
14.1;Introduction;126
14.2;Extending the Traditional View of BCL-2 Family Proteins;127
14.3;Challenging the Traditional BCL-2 Family Model;128
14.4;BCL-2 Family Proteins in the Nervous System;129
14.5;When Anti-Death BCL-2 Proteins Become Pro-Death;130
14.6;When Pro-Death BCL-2 Proteins Protect Neurons;131
14.7;Protection Predicts New Functions with a Seizure;133
14.8;BCL-2 Family Proteins Regulate Synaptic Activity;134
14.9;Conclusion;135
14.10;References;135
15;Chapter 8 Mitochondria on Guard: Role of Mitochondrial Fusion and Fission in the Regulation of Apoptosis;141
15.1;Introduction;141
15.2;Regulation of Mitochondrial Fusion and Fission;141
15.2.1;Mitochondrial Fusion;141
15.2.2;Mitochondrial Fission;142
15.3;Mitochondrial Network Dynamics and Cell Homeostasis;143
15.3.1;Mutual Relations between Cell Homeostasis and Mitochondrial Network Dynamics;143
15.3.2;Mitochondrial Dynamics and Early Development;144
15.4;Role of Mitochondrial Dynamics in Cell Death;144
15.5;Mechanism of the OMM Permeabilization: A Vital Role for Mitochondrial Fusion and Fission?;146
15.5.1;Opal and Cristae Remodeling;146
15.5.2;Mitochondrial Morphogenesis and the OMM Permeabilization;147
15.6;Emerging Evidence for the Role of BCL-2 Family Proteins in the Regulation of Mitochondrial Network Dynamics in Healthy Cells;148
15.7;Conclusion;150
15.8;References;150
16;Index;153