The Rho GTPases in Cancer (eBook)

Golen_Frontmatter.pdf 1
Golen_PartI.pdf 20
Golen_Ch01.pdf 21
Chapter 1 21
Overview of Rho GTPase History 21
Introduction 21
Evolution of Rho GTPases 22
Discovery 22
Regulation and Function of Rho-Family Members 28
Nucleotide Binding, Lipid Modification, and Subcellular Localization 28
Regulators of Rho GTPases 30
Atypical Rho GTPases 33
Upstream Signaling and Downstream Effectors and Rho Biological Processes 34
Implicating Rho GTPases in Signal Transduction 34
Linking Extracellular Signals with Rho GTPases 35
Actin Cytoskeleton Regulation 36
Protein Kinase Effectors 37
Conclusion 37
References 38
Golen_Ch02.pdf 46
Chapter 2 46
Rho Proteins in Cancer 46
Introduction 46
Rho-Family Structure 47
Rho Regulatory Proteins 48
Guanine Nucleotide Exchange Factors (GEFs) 48
GTPase-Activating Proteins (GAPs) 50
Rho Effector Interactions: General Considerations 51
Rho GTPases Drive Cell Migration 52
Conclusions 53
References 53
Golen_PartII.pdf 60
Golen_Ch03.pdf 61
Chapter 3 61
RhoGDIs in Cancer 61
GDIs Function 61
General Mechanism of Regulation of GDIs 63
GDIs in Cancer 65
Mechanism for the Biological Effects of Changing GDI Protein Levels in Cancer 67
RhoGDIs as Prognostic Indicators in Cancer 68
Tumor Suppression by HMG-CoA Inhibitors (Statins) and RhoGDI Function 69
GDIs as Drug Targets? 71
References 71
Golen_Ch04.pdf 75
Chapter 4 75
Signaling through Galpha12/13 and RGS-RhoGEFs 75
Introduction 75
RGS-RhoGEFs: Form and Function 76
RGS-RhoGEF Interaction with Other Proteins 79
Mechanisms of Regulation 79
Structural Basis of RGS-RhoGEF Function 83
DH/PH Domains 85
Physiological Functions of Ga12/13-RhoA Signaling 86
RGS-RhoGEFs and Human Disease 87
Summary 88
References 88
Golen_Ch05.pdf 93
Chapter 5 93
Vav Proteins in Cancer 93
Introduction 93
Structure, Function, and Regulation of Vav Family GEFs 94
Linking Vav Proteins to Intracellular Signaling 98
The Role of Vav Proteins in Human Cancer 100
Conclusion 103
References 104
Golen_Ch06.pdf 109
Chapter 6 109
Rho GTPase-Activating Proteins in Cancer 109
Introduction 109
Biochemical Function 110
Cellular Functions 112
Physiological Studies 113
Human Cancers 114
Deleted in Liver Cancer (DLC) 115
p190 RhoGAP 117
Chimaerins 117
Other RhoGAPs Associated with Cancer 118
Conclusions 118
References 120
Golen_PartIII.pdf 124
Golen_Ch07.pdf 125
Chapter 7 125
RhoBTB Proteins in Cancer 125
Introduction 125
RhoBTB structure 127
BTB Domains 127
Rho Domain 127
C-Terminal Domain 130
Genetic Alteration of RhoBTBs in Cancer 130
RhoBTB Signalling 131
Transcriptional Regulation by RhoBTBs 132
RhoBTBs and Cell Cycle 133
Are RhoBTBs Bona Fide Tumour Suppressors? 134
References 134
Golen_Ch08.pdf 137
Chapter 8 137
RhoC GTPase in Cancer Progression and Metastasis 137
Introduction 137
RhoA GTPase Versus RhoC GTPase (What Is the Difference?) 138
RhoC GTPase in Cancer and Metastasis 140
Conclusions 144
References 144
Golen_Ch09.pdf 149
Chapter 9 149
RhoB GTPase and FTIs in Cancer 149
Introduction 149
Unique Features of RhoB 151
Function of RhoB in Endocytic Trafficking 152
Trafficking to Lysosome, Plasma Membrane, or Nucleus 152
Trafficking Mechanisms 154
Role of RhoB in Cancer 156
Evidence for the Suppressive Role of RhoB in Neoplasia 156
Decreased Expression of RhoB in Human Cancer 157
Mechanisms of RhoB Involvement in Cancer Suppression 157
RhoB in Apoptosis by DNA Damage 159
Role of RhoB in FTI Anticancer Response 160
References 163
Golen_Ch10.pdf 168
Chapter 10 168
Regulation of Rho GTPase Activity Through Phosphorylation Events: A Brief Overview 168
Introduction 168
Modulation of RhoA GTPase Activity by Protein Kinases A and G 169
Phosphorylation of Rho Proteins by Akt/Protein Kinase B 170
Phosphorylation of RhoA and RhoC by Protein Kinase C 172
Conclusions 173
References 174
Golen_Ch11.pdf 176
Chapter 11 176
The Rho-regulated ROCK kinases in cancer 176
Introduction 176
ROCK Structure and Regulation 176
ROCK Inhibitor Specificity 179
Expression, Substrates, and Function 180
ROCK-Induced Stress Fiber Formation and Cell Adhesion 181
ROCK Functions in Embryonic Development 182
Contribution of ROCK Signaling to Cancer 183
Proliferation 184
ROCK Regulation of Proliferation: Role for the Actin Cytoskeleton 186
Signaling Pathways Influenced by ROCK 187
Mitogen-Activated Protein Kinase 187
Stat3 188
Cell Cycle Regulation 188
Cyclins and CDKs 189
CDK Inhibitors 190
ROCK and Cell Survival 192
ROCK in Tumor Cell Invasion and Metastasis 193
Migration 193
ROCK in In Vivo Models of Cancer Cell Invasion and Metastasis 194
Conclusions 195
References 195
Golen_Backmatter.pdf 206
Golen_AuthorIndex.pdf 206
Golen_SubjectIndex.pdf 215