Structure, Function and Regulation of TOR complexes from Yeasts to Mammals

by Tamanoi; Hall

• ISBN13: 9780123810052
• ISBN10: 0123810051
• Edition: 1st
• Format: Hardcover
• Copyright: 2010-10-12
• Publisher: Elsevier Science

Summary

This volume of The Enzymes features high-caliber thematic articles on the topic of glycosylphopshatidylinositol (GPI) anchoring of proteins. * Contributions from leading authorities * Informs and updates on all the latest developments in the field

Table of Contents

Preface	p. xi
mTORC1-Mediated Control of Protein Translation
Abstract	p. 1
Introduction	p. 1
mTORC1 Targets and Control of Translation	p. 5
Conclusion	p. 15
References	p. 15
The TSC1-TSC2 Complex: A Key Signal-Integrating Node Upstream of TOR
Abstract	p. 21
Introduction	p. 22
Downstream Functions: Regulation of the TOR Complexes by the TSC1-TSC2 Complex	p. 26
Upstream Regulation: The TSC1-TSC2 Complex Integrates Diverse Signals to Regulate mTORC1	p. 30
Aberrant Inhibition of the TSC1-TSC2 Complex Leading to Activation of mTORC1 in the Majority of Human Tumors	p. 38
Important Outstanding Questions Concerning the TSC1-TSC2 Complex	p. 40
References	p. 41
AMPK Control of mTOR Signaling and Growth
Abstract	p. 49
AMPK is an Energy Sensing Kinase	p. 50
mTOR is a Central Conserved Regulator of Growth and Metabolism	p. 52
AMPK Inhibits mTORC1 Through Phosphorylation of TSC2 and Raptor	p. 54
AMPK and mTOR Have Opposing Roles in Specialized Metabolic Tissues in Mammals	p. 57
AMPK and TOR Function in Model Organisms to Control Growth, Metabolism, Autophagy, and Aging	p. 60
Therapeutic Implications	p. 62
Future Perspectives	p. 66
Acknowledgments	p. 67
References	p. 68
mTOR Signaling by Amino Acid Nutrients: Involvement of MAP4K3
Abstract	p. 77
Nutrient Signaling to mTOR: Introduction	p. 78
The Sensing of Amino Acid Nutrients	p. 79
Amino Acid Transporters and mTOR Signaling	p. 82
Evidence That Intracellular Signaling Molecules Relay the Presence of Amino Acid Sufficiency to mTORC1	p. 85
MAP4K3 Participates in Amino Acid Signaling and Maintenance of Cell Size	p. 87
MAP4K3 Promotes Apoptosis via Regulation of the BH3-Only Proteins	p. 90
Acknowledgments	p. 92
References	p. 92
mTORC2: The Other Facet of mTOR
Abstract	p. 99
Structure of mTOR Complex 2 (mTORC2)	p. 100
Role of mTORC2	p. 102
Regulation of mTORC2	p. 107
Potential of mTOR Inhibitors in Cancer Treatment	p. 114
References	p. 116
TORC2 and Chemotaxis in Dictyostelium discoideum
Abstract	p. 125
Introduction	p. 126
The Life Cycle of D. discoideum	p. 127
The Components of TORC2-PDK-PKB Pathway in D. discoideum	p. 128
The Signal Transduction Pathway for Chemotaxis	p. 133
Conclusion	p. 139
Acknowledgments	p. 140
References	p. 140
The TOR-Mediated Regulation of Autophagy in the Yeast Saccharomyces cerevisiae
Abstract	p. 143
Autophagy and ATG Genes in Yeast	p. 144
Induction of Autophagy by Nutrient Limitation	p. 144
Induction of Autophagy by TOR Inactivation	p. 148
Regulation of Atg1 Kinase Complex by TOR Complex1	p. 149
Phosphorylation of Atg13 by TORC1 to Regulate Autophagy	p. 155
ULK Complex: Mammalian Counterpart of Yeast Atg1 Complex	p. 157
Concluding Remarks	p. 158
Acknowledgments	p. 160
References	p. 160
Conservation of the Tsc/Rheb/TORC1/S6K/S6 Signaling in Fission Yeast
Abstract	p. 167
Introduction	p. 168
Overview of the TSC/Rheb/TORC1 Signaling in Fission Yeast	p. 169
PAS Assay and Detection of S6 in Fission Yeast	p. 173
S6 Kinase in Fission Yeast	p. 177
Regulation of the TORC1 Signaling	p. 178
Effect of Rapamycin on the TORC1 Signaling	p. 179
Future Prospects	p. 182
Acknowledgments	p. 182
References	p. 182
The Systemic Control of Growth, Physiology, and Behavior by TOR Signaling in Drosophila
Abstract	p. 189
Introduction	p. 189
Growth Rate	p. 191
Developmental Timing	p. 195
Feeding Behavior	p. 197
Fertility	p. 198
Control of Lifespan	p. 200
References	p. 201
Cell-Intrinsic Functions and Regulation of TOR Signaling in Drosophila
Abstract	p. 205
Introduction	p. 206
Genetic Screens: Identification of Network Components and Their Relationships	p. 206
Identification and Analysis of TOR-Dependent Cellular Functions in Drosophila	p. 210
References	p. 214
TOR Signaling and Cell Death
Abstract	p. 217
Introduction: Overview of the TOR Signaling Pathway	p. 218
Anti-Cell Death Functions of TOR	p. 220
Cell Death Associated with the Upregulation of TOR	p. 226
Autophagy Protects Cells from Neurodegenerative Diseases	p. 231
Conclusions and Prospectives	p. 238
References	p. 239
Elucidating TOR Signaling in Chlamydomonas reinhardtii
Abstract	p. 245
Introduction	p. 246
Inhibition of TOR Signaling by Rapamycin in Chlamydomonas	p. 247
TOR Complexes	p. 249
Control of Autophagy by TOR	p. 254
Perspectives	p. 257
Acknowledgments	p. 257
References	p. 258
mTORC1 and mTORC2 in Energy Homeostasis
Abstract	p. 263
Introduction	p. 263
mTORC1 in the Hypothalamus	p. 264
mTORC1 in Pancreatic ß-Cells	p. 267
mTORC1 and mTORC2 in Adipose Tissue	p. 268
mTORC1 and mTORC2 in Muscle	p. 270
mTORC1 in the Liver	p. 271
Conclusion	p. 273
Acknowledgments	p. 273
References	p. 273
TOR Signaling and Aging
Abstract	p. 279
Introduction	p. 280
TOR and Aging in S. cerevisiae	p. 280
TOR and Aging in C. elegans	p. 285
TOR and Aging in Drosophila	p. 289
TOR and Aging in Mammals	p. 291
Conclusion and Future Perspectives	p. 293
Acknowledgments	p. 294
References	p. 294
mTOR Signaling and Human Cancer
Abstract	p. 301
Introduction	p. 302
Frequent Activation of the mTOR Signaling in Human Cancer	p. 303
Identification of mTOR Mutations in Human Cancer	p. 306
Inhibitors of the mTOR Signaling	p. 309
Future Prospects	p. 313
Acknowledgment	p. 314
References	p. 314
Systems Biology and TOR: Past, Present, and Future
Abstract	p. 317
Introduction	p. 318
Genome-Wide Approach to Defining the TOR Network	p. 320
Integration of Data	p. 333
Computational Modeling and Prediction	p. 336
Future: TOR and Cancer	p. 339
References	p. 342
Author Index	p. 349
Index	p. 381
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