Cover

Title page

Copyright Page

Contents

Contributors

Chapter One - Molecular Mechanisms of Noncanonical Autophagy

Abstract

1 Introduction

2 The Canonical Autophagic Pathway

2.1 The Core ATG Machinery and the Formation of Autophagosomes

2.2 Maturation of Autophagosomes

3 Noncanonical Autophagy

3.1 ULK1-Independent Autophagy

3.2 Beclin 1-Independent and VPS34-Independent Autophagy

3.3 VPS34/VPS15-Independent Autophagy

3.4 Autophagy Independent of Ubiquitin-Like Conjugation Actors

4 Conclusions

Acknowledgments

References

Chapter Two - Epigenetic Control of Gene Expression in Maize

Abstract

1 Introduction

2 McClintock's Bequest: Transposable Elements Form the Foundation of Epigenetics and Come Back Into Focus in the ``Omics´´ Era

3 The Battle Between two Genomes: Maternal and Paternal Influences on Gene Expression

4 A Puzzling and Illuminating Phenomenon: Paramutation as a Model to Study Transcriptional Silencing in Maize

5 Putting it all Together: Mutants Replace the Mystery With Mechanism

5.1 MOP1

5.2 MOP2

5.3 MOP3

5.4 RMR1

5.5 RMR2

5.6 Unstable for Orange 1 (Ufo)

5.7 Transgene Reactivated (Tgr)

6 Location, Location, Location, and Know Your Neighbors: Real Estate Rules Apply to Genomes for Cytosine Methylation and Gene Expression

7 Cultivating Diversity: Differentially Methylated Regions Coincide With Inherited Phenotypic Diversity

8 Having the Right Tool for the Job: Diversified ``RNA-Directed DNA-Methylation´´ May Have Emerged in Conjunction With the Complex Maize Genome

9 Maize Epigenetics in the Postgenomics Era

References

Chapter Three - Mitochondria in Multiple Sclerosis: Molecular Mechanisms of Pathogenesis

Abstract

1 Introduction

2 Biological Importance of Mitochondria

2.1 Mitochondrial Regulation of Energy Metabolism in the CNS

2.2 Mitochondrial Regulation of Cell Survival and Death

2.2.1 Apoptosis

2.2.2 Autophagy

2.2.3 Necrosis

3 Neurodegeneration Associated With Mitochondria

3.1 General Aspects

4 MS

4.1 Background on MS

4.2 MS Pathology: Inflammation and Neurodegeneration

5 Mitochondria and MS

5.1 Alterations of mtDNA and Mitochondrial Proteins in MS

5.2 Oxidative Stress in MS

5.3 Cellular Ionic Imbalance in MS

5.4 Apoptosis in MS

5.5 Cellular Clearance Mechanisms

6 Mitochondria as a Potential Therapeutic Target for MS

7 MS Models

7.1 In Vitro Model

7.1.1 Oligodendrocytes

7.1.2 Neurons

7.1.3 Astrocytes

7.1.4 Cocultures

7.1.5 Human Stem Cell-Derived Neural Cells

7.1.6 Brain Slices

7.2 In Vivo Model

7.2.1 EAE

7.2.2 Cuprizone Model

8 Conclusions and Perspectives

Acknowledgments

References

Chapter Four - Molecular Regulation of the Spindle Assembly Checkpoint by Kinases and Phosphatases

Abstract

1 Introduction

2 The Spindle Assembly Checkpoint: Inducers, Actors, and Effectors

2.1 Sensing Microtubule Attachment by SAC

2.2 SAC Activation and SAC Silencing

3 Kinases Involved in the Spindle Assembly Checkpoint

3.1 MPS1

3.1.1 Recruitment of MPS1 to the Outer KT

3.1.2 Role of MPS1 in the SAC

3.2 Aurora B

3.2.1 Indirect Contribution of Aurora B to the SAC

3.2.2 Direct Contribution of Aurora B to the SAC

3.2.3 Other SAC-Related Functions of Aurora B

3.3 BUB1

3.3.1 Regulation of Sister Chromatid Biorientation by BUB1

3.3.2 Involvement of the Kinase Activity of BUB1 in the SAC

3.4 PLK1

3.4.1 Role of PLK1 in the SAC

3.4.2 Interplays Between PLK1 and SAC Kinases

4 Phosphatases Involved in the Spindle Assembly Checkpoint

4.1 PP1

4.1.1 PP1 Recruitment to the Outer Kinetochore

4.1.2 PP1 Activity in the SAC

4.2 PP2A

4.2.1 Impact of PP2A Activity in Mitosis and SAC

4.2.2 Role of PP2A in Sister Chromatid Cohesion

5 Conclusions

Acknowledgments

References

Chapter Five - BH3-Only Proteins in Health and Disease

Abstract

1 Introduction

2 Between the Quick and the Dead

3 Fidelity Versus Promiscuity

4 The Activation Conundrum

5 BH3-Only Proteins, Homeostasis, and Development: It's a Matter of Life and Death

5.1 BH3-Only Proteins and Homeostasis

5.1.1 If No Phenotype, Cross it With Bim-/-

5.1.2 Breaking Bad: Beyond Apoptosis

5.2 BH3-Only Proteins and Diseases

5.2.1 BH3-Only Proteins and Tumor Development

5.2.2 BH3-Only Proteins in Sepsis

5.2.3 BH3-Only Proteins in Cardiomyopathy

5.2.4 BH3-Only Proteins in Diabetes

5.2.5 BH3-Only Proteins in Neurodegenerative Disorders

5.2.6 BH3-Only Proteins in Arthritic Diseases

5.2.7 BH3-Only Proteins in Hepatic Disorders

5.2.8 BH3-Only Proteins in Autoimmune Disorders

6 Concluding Remarks

Acknowledgments

References

Chapter Six - The Multifaceted Contributions of Chromatin to HIV-1 Integration, Transcription, and Latency

Abstract

1 Introduction

1.1 HIV-1 Infection

1.2 HIV-1 Replication and Latency

1.3 Role of Chromatin in HIV-1 Replication

2 Role of Chromatin in HIV-1 Integration

2.1 Mechanism of Integration

2.2 Distribution of HIV-1 Integration Sites

2.3 Position of HIV-1 Integration in Latency

2.3.1 Mechanistic Insights From In Vitro HIV-1 Latency Models

2.3.2 HIV-1 Integration Site Distribution in Patient Latent Reservoir

2.4 Nuclear Architecture as Topological Determinant of HIV-1 Integration Site Distribution

2.5 Cellular Proteins Involved in PIC Nuclear Import and DNA Targeting

2.5.1 Nuclear Transport Components

2.5.2 Cleavage and Polyadenylation Specific Factor (CPSF6)

2.5.3 Lens Epithelium-Derived Growth Factor (LEDGF/p75)

2.5.4 Integrase Interactor 1 (INI-1)

3 Role of Chromatin in HIV-1 LTR Transcription and Latency

3.1 Basal HIV-1 Transcription

3.1.1 Transcription Factors Regulating the HIV-1 LTR

3.1.2 RNA Pol II Pausing at the HIV-1 LTR

3.1.3 Nucleosome Positioning at the HIV-1 LTR

3.2 Chromatin Modifiers and the LTR Nucleosomal Structure

3.2.1 ATP-Dependent Chromatin Remodelers

3.2.2 Histone Modifying Complexes

3.3 Tat-Mediated HIV-1 Transcription

3.3.1 Recruitment of the Super Elongation Complex

3.3.2 Tat Coactivating Complexes

4 Chromatin: a Druggable Target in HIV-1 Therapeutics

4.1 LEDGINs

4.2 Targeting HIV-1 Latency: The Shock and Kill Approach

4.2.1 Latency Reversal Agents

5 Concluding Remarks

Acknowledgments

References

Chapter Seven - The Inflammatory Signal Adaptor RIPK3: Functions Beyond Necroptosis

Abstract

1 Introduction

2 RIPK3 Functions as an Essential Adaptor for Necroptosis

2.1 Phosphorylation-Driven Activation of RIPK3

2.2 RHIM-Mediated Formation of RIPK3 Oligomer During Necroptosis

3 Negative Regulatory Mechanisms of Necroptosis

3.1 Endogenous Necroptosis Inhibitory Proteins

3.2 Viral Necroptosis Inhibitory Proteins

4 How Does RIPK3 Promote Inflammation?

5 Nonnecrotic Functions of RIPK3

5.1 RIPK3 in NF-?B Activation

5.2 RIPK3 in Inflammasome Activation

5.3 RIPK3 Functions in Apoptosis

5.4 Necroptosis-Independent Functions of RIPK3 in Inflammatory Diseases

6 Concluding Remarks

References

Index

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