Clusterin (eBook)

Front Cover 4
Advances in Cancer Research 4
Copyright Page 5
Contents 6
Contributors 10
Chapter 1: Introduction 12
I. Introduction 12
Acknowledgments 18
References 18
Chapter 2: From One Gene and Two Transcripts to Many Proteins 20
I. Introduction 21
II. CLU Gene Organization, Promoter Region, and Transcription Products 22
III. CLU Protein Forms 29
IV. Conclusions 30
Acknowledgments 31
References 32
Chapter 3: The Shifting Balance Between CLU Forms During Tumor Progression 36
I. Introduction 36
II. Shifting of Cell Metabolism in Tumorigenesis 37
III. Shifting of CLU Forms During Tumor Progression 38
IV. Concluding Remarks 42
Acknowledgments 42
References 42
Chapter 4: Clusterin Activity by Calcium 44
I. Introduction 45
II. Ca2+ Signal 45
III. Ca2+ Contribution to CLU-Mediated Effects 46
IV. Ca2+ Influx Through TRPM-2 Channels and CLU Location 48
V. Ca2+ And Cell Proliferation 49
VI. Is CLU a Ca2+-Dependent Pro- or Antiapoptotic Gene? 50
VII. Ca2+ Homeostasis and CLU Transcription 54
VIII. CLU Translocations in Response to Ca2+ Signal 58
IX. ER Stress, Unfolded Protein Response, Ca2+, and CLU 59
X. Ca2+, Clusterin, and DNA Repair 61
XI. Conclusions 62
Acknowledgments 63
References 63
Chapter 5: Nuclear CLU (nCLU) and the Fate of the Cell 70
I. Introduction: Where is CLU? 71
II. Preliminary Remarks Before Dealing with nCLU: The Possible Action of sCLU as Differentiating Agent 73
III. A Brief History of nCLU 75
IV. CLU Expression and Localization in the Regressing Rat Ventral Prostate 76
V. CLU was Found Positively Linked to Apoptosis and Negatively Linked to Proliferation: The Early Years (1993-1995)... 78
VI. CLU and Follicular Atresia, Another Model of Tissue Involution Linked to Apoptosis 80
VII. CLU Expression was Found Associated to Nonapoptotic Cell Death 80
VIII. CLU Expression was Found Associated to Lesions in Central and Peripheral Nervous System 81
IX. Increased CLU Expression is Linked to Inhibition of Proliferation and Induction of Cell Differentiation 82
X. Early Studies on Translational Upregulation of CLU During Apoptosis: The Role of NF1 83
XI. CLU Gene Expression and Cell Death Induced by Vitamin D (Calcitriol) and Tamoxifen (Tam): Implication in Chemioresist... 84
XII. Early Observations: CLU Expression is Induced by TGF-Beta 1 NF-Kappa B Inhibitors Blocked the Secretion of CLU...
XIII. 1996: nCLU Finally Appears in the Literature 86
XIV. A Role For nCLU in the Nucleus: Binding to Ku70 88
XV. nCLU Today: The Dark Side of the Moon Revealed 89
XVI. The Molecular Mechanisms of Production of nCLU are Still Sketchy 91
XVII. In the End: Is Targeting of CLU to the Nucleus an Experimental Artifact? 94
XVIII. Conclusions 95
Acknowledgments 96
References 96
Chapter 6: The Chaperone Action of Clusterin and Its Putative Role in Quality Control of Extracellular Protein Folding 100
I. Introduction 101
II. Clusterin as a Chaperone 103
III. In Vivo Insights into the Chaperone Action of Clusterin 107
IV. Other Extracellular Chaperones (ECs) and a Model For Quality Control (QC) of Extracellular Protein Folding... 109
V. Future Research Directions 114
VI. Conclusion 118
References 118
Chapter 7: Cell Protective Functions of Secretory Clusterin (sCLU) 126
I. Introduction 126
II. sCLU-A Component of High-Density Lipoproteins 127
III. sCLU in Apoptosis-Signaling Toward Cell Survival? 128
IV. sCLU in the Removal of Dead Cells and Cellular Debris 131
V. sCLU in Immune Modulation 134
VI. Role of sCLU in Amyloid Beta (Abeta) Clearance in M. Alzheimer 137
VII. Conclusions and Perspectives 139
References 140
Chapter 8: Clusterin: A Multifacet Protein at the Crossroad of Inflammation and Autoimmunity 150
I. Introduction 151
II. Inflammation, the Danger Signal, and Autoimmunity 152
III. Immune System Homeostasis and Regulation: The Common Purpose of Autoimmunity and Cancer 153
IV. Inflammation 153
V. The Place and Role of CLU In Autoimmune Diseases (Table I and Fig. 1) 161
VI. Concluding Remarks 172
References 174
Chapter 9: Oxidative Stress in Malignant Progression: The Role of Clusterin, A Sensitive Cellular Biosensor of Free Radicals.. 182
I. Introduction 183
II. Molecular Effects of Altered Oxidative Load in Human Cells 184
III. Oxidative Injury in Ageing and Age-Related Diseases 188
IV. Oxidative Stress in Malignant Progression 190
V. Clusterin as a Sensitive Cellular Biosensor of Oxidative Stress 192
VI. Concluding Remarks-Perspectives 202
Acknowledgments 206
References 206
Color Plates 227