Maiese Forkhead Transcription Factors

Vital Elements in Biology and Medicine
1. Auflage 2010
ISBN: 978-1-4419-1599-3
Verlag: Springer US
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, Band 665, 292 Seiten

Reihe: Advances in Experimental Medicine and Biology

Forkhead Transcription Factors: Vital Elements in Biology and Medicine provides a unique platform for the presentation of novel work and new insights into the vital role that forkhead transcription factors play in multiple systems throughout the body. Leading international authorities provide their knowledge and insights to offer a novel perspective for translational medicine that highlights the role of forkhead genes and proteins that may have the greatest impact for the development of new strategies for a broad array of disorders. Equally important, Forkhead Transcription Factors: Vital Elements in Biology and Medicine clearly sets a precedent for the necessity to understand the diverse and complex nature of forkhead proteins since this family of transcription factors can limit as well as foster disease progression depending upon the cellular environment. The presentation and discussion of innovative studies and especially those that examine previously unexplored pathways that may influence clinical survival and longevity offer an exciting approach to address the potential of forkhead transcription factors for new therapeutic avenues in multiple disciplines.

KENNETH MAIESE is a physicianscientist whose interests focus on the basic and clinical mechanisms that control neuronal and vascular longevity and immune system function. He presently is the Chief of the Division of Cellular and Molecular Cerebral Ischemia and is a Professor in the Departments of Neurology and Anatomy and Cell Biology, the Center for Molecular Medicine and Genetics, the Barbara Ann Karmanos Cancer Institute, and the National Institute of Environmental Health Sciences at Wayne State University School of Medicine. Dr. Maiese graduated from the University of Pennsylvania Suma cum Laude with Distinction and received his medical degree as a Teagle and Grupe Foundation Scholar from Weill Medical College of Cornell University. He obtained his internship and residency at The New York Hospital-Cornell Medical Center and subsequently completed his clinical and basic science postdoctoral training at Cornell and the National Institute of Aging. Dr. Maiese has been fortunate to receive recognition with outstanding teaching awards and election to America's Top Physicians and The Best of U.S. Physicians. His investigations are designed to translate basic science into successful therapeutic treatments for conditions such as cancer, metabolic disorders, cardiovascular disease, diabetes, stroke, and Alzheimer's disease. His work has received the distinction of 'High Impact Research and Potential Public Health Benefit' by the National Institutes of Health with continuous funding from sources that include the American Diabetes Association, the American Heart Association, the Bugher Foundation, a Johnson and Johnson Focused Giving Award, and the National Institutes of Health. He chairs national grant committees and is a chartered panel member or consultant for several national and international foundations as well as multiple study sections and special emphasis panels for the National Institutes of Health. Dr. Maiese serves as the Editor-in-Chief for two international journals as well an Associate Editor or a member of the editorial board for several journals, executive committees, technology transfer panels, and scientific advisory councils. Given the broad applications of his work, Dr. Maiese is frequently honored as the chairperson and/or the plenary speaker for a number of international symposiums in a range of disciplines that include cell biology, neuroscience, vascular biology, cardiac disease, molecular oncology, and renal physiology.

Autoren/Hrsg.

Maiese, Kenneth

Inhaltsverzeichnis

1;PREFACE;6
2;ABOUT THE EDITOR...
;8
3;PARTICIPANTS;9
4;Table of Contents
;14
5;SECTION I Insights into Immunity ,Infection and Cancer ;21
5.1;CHAPTER 1 FOXO1, T-Cell Trafficking and Immune Responses
;22
5.1.1;Abstract;22
5.1.2;Introduction;22
5.1.3;Mechanisms of T-Cell Homing into Lymph Nodes
;22
5.1.4;FOXO1, L-Selectin and T-Cell Homing
;24
5.1.5;FOXO1 and T-Cell Proliferation
;26
5.1.6;New Potential Targets of FOXO1 to Impose T-Cell Fate
;28
5.1.7;FOXO1, T-Cell Egress and Peripheral Homing
;29
5.1.8;Conclusion;30
5.1.9;References;32
5.2;CHAPTER 2 FOXP3 and Its Role in the Immune System
;36
5.2.1;Abstract;36
5.2.2;Introduction;36
5.2.3;Structure and Function of FOXP3
;37
5.2.4;Expression of FOXP3
;38
5.2.5;Ontogeny and Migration of FOXP3+ Cells
;39
5.2.6;Mechanisms of Suppression Mediated by FOXP3+ T-Cells
;40
5.2.7;Role of FOXP3+T-Cellsin Suppression of Diseases
;42
5.2.8;Functions of FOXP3 in Nonhematopoietic Cells
;43
5.2.9;Concluding Remarks
;43
5.2.10;References;43
5.3;CHAPTER 3 Molecular Regulation of Cellular Immunity by FOXP3 ;49
5.3.1;Abstract;49
5.3.2;Introduction;49
5.3.3;Discovery of FOXP3 and Key Structural Features
;50
5.3.4;Phenotype and Function of FOXP3+ Treg Cells
;51
5.3.5;Role of FOXP3 in the Development of Treg Cells
;51
5.3.5.1;Naturally Occurring versus Induced Treg Cells;51
5.3.5.2;Reprogramming CD4+T-Cells into Treg Cells by Ectopic Expression of FOXP3
;52
5.3.6;Role of FOXP3 in Conventional T-Cells
;53
5.3.7;Molecular and Cellular Biology of IPEX
;53
5.3.8;Isoforms of FOXP3 in Humans
;54
5.3.9;FOXP3 Protein Interactions;55
5.3.9.1;Homo-Oligomerization;55
5.3.9.2;Interactions with NFAT;55
5.3.9.3;Interactions with API;55
5.3.9.4;Interactions with NFKB;56
5.3.9.5;Interactions with Runx1;56
5.3.9.6;Interaction with ROR-a
;56
5.3.9.7;Interaction with ROR-.t
;56
5.3.10;The FOXP3-TIP60-HDAC7 Complex
;57
5.3.10.1;Interaction with HDAC9;57
5.3.11;Post-Translational Modifications of FOXP3
;57
5.3.12;Epigenetic Regulation of FOXP3 and Its Target Genes
;58
5.3.12.1;Epigenetics of Genes Regulated by FOXP3
;58
5.3.12.2;Epigenetic Regulation of FOXP3 Expression
;58
5.3.13;Role of FOXP3 in Treg versus 1h17 Cell Development
;59
5.3.14;Conclusion;60
5.3.15;References;60
5.4;CHAPTER 4 The Biology of FoxP3: AKey Player in Immune Suppression during Infections, Autoimmune Diseases and Cancer ;66
5.4.1;Abstract;66
5.4.2;Introduction;66
5.4.3;The Discovery of FoxP3
;66
5.4.4;Functional and Structural Features of FoxP3
;67
5.4.4.1;Forkhead Domain
;67
5.4.4.2;Leucine Zipper Domain;68
5.4.4.3;Forkhead- Leucine Zipper Linker Region;68
5.4.4.4;N-Terminal Proline Rich Repressor Domain
;68
5.4.4.5;Multiple Isoforms and Subcellular Localization
;69
5.4.5;FoxP3 Regulation and Function;69
5.4.5.1;Role of FoxP3 in Developmentand Function of Tregs
;69
5.4.5.2;Cell Extrinsic Regulation of FoxP3
;70
5.4.5.3;Epigenetic and Posttranslational Regulation of Foxp3
;70
5.4.6;Role of FoxP3 in Cancer
;71
5.4.7;FoxP3 in Infectious Diseases;71
5.4.7.1;Parasitic Infections;71
5.4.7.2;ViralInfections;72
5.4.7.3;HIV Infection
;72
5.4.8;Foxp3 in Transplantation Tolerance;72
5.4.9;FoxP3 in Autoimmune Diseases;73
5.4.9.1;Multiple Sclerosis;73
5.4.9.2;Inflammatory Bowel Diseases
;73
5.4.9.3;Type I Diabetes;73
5.4.10;Emerging and Potential Therapeutic Intervention;73
5.4.11;References;75
6;SECTION II Elucidating the Components Responsible for Vascular Development and Disease in the Cardiovascular System;79
6.1;CHAPTER 5 The Cooperative Roles of Foxcl and Foxc2 in Cardiovascular Development ;80
6.1.1;Abstract;80
6.1.2;Introduction;80
6.1.3;FoxC1 and FoxC2 Proteins
;80
6.1.4;Overlapping Expression of
Foxcl and Foxc2 during Development;81
6.1.5;Developmental Defects in Foxc Mutant Mouse Embryos
;81
6.1.6;Mutations in FOXC1 and FOXC2 Genes Associated with Developmental Disorders in Humans
;82
6.1.7;Cooperative Roles of Foxc1 and Foxc2 in Cardiovascular Development
;83
6.1.8;Foxc Function in Arterial Specification;83
6.1.9;Foxc Function in Lymphatic Vessel Development;85
6.1.10;Foxc Function in Angiogenesis;85
6.1.11;Foxc Function in the Second Heart Field;87
6.1.12;Foxc Function in Cardiac Neural Crest Cells
;89
6.1.13;Foxc Function in Epicardial-Derived Cells;89
6.1.14;Future Directions;90
6.1.15;References;91
6.2;CHAPTER 6 FoxO Proteins and Cardiac Pathology
;95
6.2.1;Abstract;95
6.2.2;The FoxO Family
;95
6.2.3;The Spectrum of Transcriptional Responses Mediated by FoxO Family Members
;95
6.2.4;Regulation of FoxO Proteins
;96
6.2.4.1;Phosphorylation;96
6.2.4.2;Ubiquitinization;97
6.2.4.3;Acetylation;98
6.2.5;Transcriptional Partners of FoxO
;98
6.2.6;FoxO Transcription Factors in Cardiac Pathology
;99
6.2.6.1;Myocardial Ischemia and Post-Ischemic Reperfusion
;99
6.2.6.2;Hypertrophy;101
6.2.6.3;Development;102
6.2.7;Conclusion;102
6.2.8;References;102
6.3;CHAPTER 7 The Forkhead Transcription Factors Play Important Roles in Vascular Pathology and Immunology
;107
6.3.1;Abstract;107
6.3.2;Introduction;107
6.3.3;Introduction of the FOX Transcription Factor Superfamily
;108
6.3.3.1;Structure;108
6.3.3.2;Expression;108
6.3.3.3;Functional Modes of FOX Transcription Factors
;108
6.3.3.4;Combinatorial Regulation of Gene Expression by FOX Transcription Factorsand Other Transcription Factors ;109
6.3.3.5;Post-Translational Modification
;109
6.3.4;FOX Transcription Factors and Endothelial Cell Pathology;110
6.3.4.1;Endothelial Apoptosis;110
6.3.4.2;EPC Apoptosis and Maturation
;111
6.3.4.3;Endothelial Cell Proliferation;111
6.3.4.4;Roles of FOX Transcription Factors in VEGF Signaling
;112
6.3.4.5;Endothelial Responses to Stress
;112
6.3.4.6;Neovascularization;113
6.3.5;FOX Transcription Factors and Vascular Smooth Muscle Cells (VSMCs)
;113
6.3.5.1;VSMC Apoptosis
;113
6.3.5.2;VSMC Proliferation;113
6.3.5.3;FoxO in VSMC Differentiation
;114
6.3.5.4;FoxO in Aging VSMCs;114
6.3.5.5;Roles of Other FOX Transcription Factors in VSMCs
;114
6.3.6;FOX Transcription Factors, Inflammation and Immune System;115
6.3.6.1;FOX Transcription Factors and Inflammation
;115
6.3.6.2;FoxP3, Regulatory T-Cells and Immune Suppression
;116
6.3.6.3;FoxNl and Thymocyte Development;117
6.3.6.4;FOX Transcription Factorsand T-Cell Activation
;117
6.3.7;Conclusion;117
6.3.8;References;118
6.4;CHAPTER 8 Regulatory T-Cells, FoxP3 and Atherosclerosis
;123
6.4.1;Abstract;123
6.4.2;Atherosclerosis, Inflammation and Autoimmunity;123
6.4.3;Regulatory T-Cells, Developmental and Functional Aspects;123
6.4.4;FoxP3 in Experimental Models of Autoimmunity and Atherosclerosis
;126
6.4.5;Foxp3, Regulatory T-Cells and Atherosclerosis in Humans;127
6.4.6;Treg and Atherosclerosis: Prospects;128
6.4.7;References;129
7;SECTION III Dissecting the Pathways of Neuronal Integration and Plasticity in the Nervous System ;132
7.1;CHAPTER 9 FOXP Genes, Neural Development, Speech and Language Disorders ;133
7.1.1;Abstract;133
7.1.2;Introduction;133
7.1.3;TheFoxp Subfamily
;134
7.1.4;Discovery of FOXP2 asa 'Language Gene'
;134
7.1.5;FOXP2 and Specific Language Impairment (SLI) and Autism ;135
7.1.6;Expression of Foxp SubfamilyMembers in the Brain
;135
7.1.6.1;Basal Ganglia;136
7.1.6.2;Cerebral Cortex and Hippocampus
;137
7.1.6.3;Thalamus;138
7.1.6.4;Cerebellum;139
7.1.6.5;Spinal Cord;139
7.1.7;Language Impairments in the Affected Members of the KE Family
;139
7.1.8;Imaging Studies on the KE Family;139
7.1.9;The FOXP2 Expression Pattern in the Brain and Its Relation to the Cognitive Functions of Speechand Language ;139
7.1.10;Phenotype in Foxp2 Mutant Mice;140
7.1.11;Transcriptional Activity of the FOXP2 Protein
;141
7.1.12;Foxp2 Upstream and Downstream Genes (Fig. 2);141
7.1.13;Perspectives;142
7.1.14;References;143
7.2;CHAPTER 10 Pathophysiological Relevance of Forkhead Transcription Factorsin Brain Ischemia
;146
7.2.1;Abstract;146
7.2.2;FOXO Phosphorylation Regulating Shuttlingbetween Nucleus and Cytoplasm
;146
7.2.3;FOXO Phosphorylation in Response to Oxidative and Ischemic Stresses
;148
7.2.4;Decreased Akt Activity following Brain Ischemia Triggers Activation of Proapoptotic Proteins
;149
7.2.5;Dephosphorylation and Activation of FOXOs following Brain Ischemia
;149
7.2.6;Crosstalk between Akt and Calcineurin Signaling in Neuronal Death
;150
7.2.7;Synergistic Activation of Fas-Ligand Promoter by NFATs and FOXOs
;150
7.2.8;Downstream Targets for FOXOI in Delayed Neuronal Death;152
7.2.9;Regulation of FOXO Pathways by SIRT1;153
7.2.10;Therapeutic Perspectives;153
7.2.11;References;155
7.3;CHAPTER 11 New Insights for FOXO and Cell-Fate Decision in HIV Infection and HIV Associated Neurocognitive Disorder ;159
7.3.1;Abstract;159
7.3.2;Introduction;159
7.3.2.1;FOXO Family Members and General Function
;159
7.3.2.2;Regulation of FOXO Protein Activity
;160
7.3.3;FOXO in HIV-1 Infection and HIV-1 Associated Neurocognitive Disorders
;162
7.3.4;FOXO in T-Cell Depletion
;163
7.3.4.1;Potential Signaling Pathway of FOX03a in T-Cell Depletion
;163
7.3.4.2;FOX03a Commits to the Survival o/CentralMemory CD4+ T-Cell in HIV Injection
;164
7.3.5;FOXO in Macrophage/Monocyte Pathology of HIV-1 Infection
;164
7.3.5.1;The Potential Relationship of FOXO Proteins and Viral Replicationin Macrophage
;165
7.3.5.2;The DualRole of FOX03a in HIV Infection in Macrophages
;165
7.3.6;FOXO and HIV-1 Mediated Central Nervous System Damage
;166
7.3.6.1;FOXO Proteins in the Regulation of Stem Cell Homeostasis in the Nervous System
;168
7.3.6.2;FOXO Proteins Are Pivotal Factors in Neuronal Apoptosis
;169
7.3.6.3;FOX03a in Proinflammatory Cytokine-Induced Astrogliosis
;170
7.3.6.4;Summary and Future Directions;170
7.3.7;References;171
8;SECTION IV Translating Vital Cellular Mechanisms into Successful Clinical Care
;176
8.1;CHAPTER 12 FOXP3+ Regulatory T-Cells in Chronic Kidney Disease: Molecular Pathways and Clinical Implications;177
8.1.1;Abstract;177
8.1.2;Introduction;177
8.1.3;Pathobiology of CD4+/FOXP3+ Regulatory T-Cells
;178
8.1.4;Forkhead BoxP3 and T-Cell Receptor Signalingin Tregs;179
8.1.5;Costimulatory Signaling Pathways and FOXP3 Expression
;179
8.1.6;Interleukin-2 and FOXP3 Expression
;179
8.1.7;Impaired CD4+/FOXP3+ Regulatory T-Cell Functionin Patients with ESKD
;180
8.1.8;Place of oxLDL in Tregs Apoptosis in Patients with ESKD ;180
8.1.9;Place of 26S Proteasome in Tregs Apoptosis;180
8.1.10;FOXP3+ Regulatory T-Cells Apoptosis in Uremia: Role of the 26S Proteasome ;181
8.1.11;Conclusion;182
8.1.12;References;182
8.2;CHAPTER 13 Transcriptional Role of FOXOIinDrug Resistance through AntioxidantDefense Systems
;185
8.2.1;Abstract;185
8.2.2;Introduction;185
8.2.3;Differential Expression of FOXOl in Cancer Cells
;186
8.2.4;Induction and Translocation of FOXOl by Paclitaxel in Cancer Cell Lines;186
8.2.5;FOXOI Attenuates Sensitivity to Paclitaxel-Induced Cell Death in Paclitaxel Resistant Cell Lines ;189
8.2.6;Attenuation of Oxidative Stress byPaclitaxel and FOXO1 in Ovarian Cancer Cell Lines;190
8.2.7;MnSOD Expression in Paclitaxel Sensitive and Resistant Ovarian Cancer Cell Lines and Ovarian Cancer Samples
;190
8.2.8;References;193
8.3;CHAPTER 14 Foxp3 Expressing Regulatory T-Cells in Allergic Disease ;194
8.3.1;Abstract;194
8.3.2;Introduction;194
8.3.3;Background;195
8.3.4;Regulatory T-Cells in Health and Allergic Conditions;196
8.3.4.1;Health;197
8.3.4.2;Experimental Models
;197
8.3.4.3;Allergic Rhinitis and Asthma
;198
8.3.4.4;Mucosal System;199
8.3.4.5;Atopy;200
8.3.4.6;Atopic Dermatitis;200
8.3.5;Modulation of TRegs with Treatment
;201
8.3.5.1;Glucocorticoids;201
8.3.5.2;Specific Allergen Immunotherapy;202
8.3.5.3;Venom Immunotherapy
;203
8.3.6;Conclusion;204
8.3.7;References;205
8.4;CHAPTER 15 Human Clinical Phenotype Associated with FOXN1 Mutations
;209
8.4.1;Abstract;209
8.4.2;Introduction: Severe Combined Immunodeficiencies;209
8.4.3;The Nude/SCID Phenotype;211
8.4.4;Fox Family Members and Immune System;215
8.4.5;FOXNl Skin Specific Expression and T-Cell Development
;217
8.4.6;References;218
8.5;CHAPTER 16 FOXL2:At the Crossroads of Female Sex Determination and Ovarian Function;221
8.5.1;Abstract;221
8.5.2;Introduction;221
8.5.3;FoxL2 Protein Sequence Is Highly Conserved;222
8.5.4;Expression of FOXL2
;222
8.5.5;Disease-Causing FOXL2 Mutations in Humans
;223
8.5.5.1;Intragenic FOXL2 Mutations
;223
8.5.5.2;Missense Mutations;223
8.5.5.3;Nonsense or Early Stop Codon-Inducing Frameshift Mutations;224
8.5.5.4;Frameshift Mutations Leading to Elongated Proteins;225
8.5.5.5;PolyAlanine Length Variations;225
8.5.5.6;Chromosomal Rearrangement and Extragenic Mutations Leadingto BPES
;225
8.5.5.7;A Genotype/Phenotype Correlation?;226
8.5.5.8;Learning from MiceModels
;226
8.5.6;Regulation of the Expression and Activity of FOXL2
;227
8.5.7;Regulation of Target Genes and of Cellular Functions by FOXL2
;231
8.5.7.1;FOXL2 Targets in the Pituitary;231
8.5.7.2;FOXL2 Targets in the Ovary;231
8.5.7.3;The FOXL2 Response Element (FLRE) and Its Specificity
;235
8.5.8;Conclusion;236
8.5.9;References;236
8.6;CHAPTER 17 FOXO Transcription Factors: From Cell Fate Decisions to Regulation of Human Female Reproduction;241
8.6.1;Abstract;241
8.6.2;Introduction;241
8.6.3;Regulation of FOXO Activity
;242
8.6.4;FOXO and Cell Fate
;243
8.6.4.1;Cell Cycle Progression, Checkpoint Control and Apoptosis
;244
8.6.4.2;Cellular Stress Response and Longevity
;245
8.6.4.3;Tumor Suppression
;246
8.6.5;FOXO and the Endometrium
;247
8.6.5.1;Endometrial Differentiation and Menstrual Shedding
;247
8.6.5.2;The Decidua of Pregnancy
;249
8.6.5.3;Endometriosis and Endometrial Cancer
;249
8.6.6;FOXO and the Ovary
;250
8.6.6.1;Follicular Development and Ovulation
;250
8.6.6.2;Primary Ovarian Insufficiency;251
8.6.7;References;251
8.7;CHAPTER 18 The "O" Class: Crafting Clinical Care with FoxO Transcription Factors ;256
8.7.1;Abstract;256
8.7.2;Abbreviations;256
8.7.3;Introduction;257
8.7.4;FoxO Protein Expression;257
8.7.5;FoxO Protein Structure and Function as Transcription Factors;257
8.7.6;FoxO Proteins, Posttranslational Modulation, Novel Signal Transduction Pathways, and Cell Cycle Regulation
;258
8.7.7;FoxO Proteins, Metabolism and Cell Longevity;262
8.7.8;FoxO Proteins, Stem Cells and Cardiovascular Development
;264
8.7.9;FoxO Proteins and the Immune System;265
8.7.10;FoxO Proteins and Cancer;266
8.7.11;Conclusions and Future Perspectives for Clinical Care;267
8.7.12;References;268
9;INDEX;275