The Enzymes: Structure, Function and Regulation of Tor Complexes from Yeasts to Mammals

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  • Edition: 1st
  • Format: Hardcover
  • Copyright: 2010-10-01

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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

Prefacep. xi
mTORC1-Mediated Control of Protein Translation
Abstractp. 1
Introductionp. 1
mTORC1 Targets and Control of Translationp. 5
Conclusionp. 15
Referencesp. 15
The TSC1-TSC2 Complex: A Key Signal-Integrating Node Upstream of TOR
Abstractp. 21
Introductionp. 22
Downstream Functions: Regulation of the TOR Complexes by the TSC1-TSC2 Complexp. 26
Upstream Regulation: The TSC1-TSC2 Complex Integrates Diverse Signals to Regulate mTORC1p. 30
Aberrant Inhibition of the TSC1-TSC2 Complex Leading to Activation of mTORC1 in the Majority of Human Tumorsp. 38
Important Outstanding Questions Concerning the TSC1-TSC2 Complexp. 40
Referencesp. 41
AMPK Control of mTOR Signaling and Growth
Abstractp. 49
AMPK is an Energy Sensing Kinasep. 50
mTOR is a Central Conserved Regulator of Growth and Metabolismp. 52
AMPK Inhibits mTORC1 Through Phosphorylation of TSC2 and Raptorp. 54
AMPK and mTOR Have Opposing Roles in Specialized Metabolic Tissues in Mammalsp. 57
AMPK and TOR Function in Model Organisms to Control Growth, Metabolism, Autophagy, and Agingp. 60
Therapeutic Implicationsp. 62
Future Perspectivesp. 66
Acknowledgmentsp. 67
Referencesp. 68
mTOR Signaling by Amino Acid Nutrients: Involvement of MAP4K3
Abstractp. 77
Nutrient Signaling to mTOR: Introductionp. 78
The Sensing of Amino Acid Nutrientsp. 79
Amino Acid Transporters and mTOR Signalingp. 82
Evidence That Intracellular Signaling Molecules Relay the Presence of Amino Acid Sufficiency to mTORC1p. 85
MAP4K3 Participates in Amino Acid Signaling and Maintenance of Cell Sizep. 87
MAP4K3 Promotes Apoptosis via Regulation of the BH3-Only Proteinsp. 90
Acknowledgmentsp. 92
Referencesp. 92
mTORC2: The Other Facet of mTOR
Abstractp. 99
Structure of mTOR Complex 2 (mTORC2)p. 100
Role of mTORC2p. 102
Regulation of mTORC2p. 107
Potential of mTOR Inhibitors in Cancer Treatmentp. 114
Referencesp. 116
TORC2 and Chemotaxis in Dictyostelium discoideum
Abstractp. 125
Introductionp. 126
The Life Cycle of D. discoideump. 127
The Components of TORC2-PDK-PKB Pathway in D. discoideump. 128
The Signal Transduction Pathway for Chemotaxisp. 133
Conclusionp. 139
Acknowledgmentsp. 140
Referencesp. 140
The TOR-Mediated Regulation of Autophagy in the Yeast Saccharomyces cerevisiae
Abstractp. 143
Autophagy and ATG Genes in Yeastp. 144
Induction of Autophagy by Nutrient Limitationp. 144
Induction of Autophagy by TOR Inactivationp. 148
Regulation of Atg1 Kinase Complex by TOR Complex1p. 149
Phosphorylation of Atg13 by TORC1 to Regulate Autophagyp. 155
ULK Complex: Mammalian Counterpart of Yeast Atg1 Complexp. 157
Concluding Remarksp. 158
Acknowledgmentsp. 160
Referencesp. 160
Conservation of the Tsc/Rheb/TORC1/S6K/S6 Signaling in Fission Yeast
Abstractp. 167
Introductionp. 168
Overview of the TSC/Rheb/TORC1 Signaling in Fission Yeastp. 169
PAS Assay and Detection of S6 in Fission Yeastp. 173
S6 Kinase in Fission Yeastp. 177
Regulation of the TORC1 Signalingp. 178
Effect of Rapamycin on the TORC1 Signalingp. 179
Future Prospectsp. 182
Acknowledgmentsp. 182
Referencesp. 182
The Systemic Control of Growth, Physiology, and Behavior by TOR Signaling in Drosophila
Abstractp. 189
Introductionp. 189
Growth Ratep. 191
Developmental Timingp. 195
Feeding Behaviorp. 197
Fertilityp. 198
Control of Lifespanp. 200
Referencesp. 201
Cell-Intrinsic Functions and Regulation of TOR Signaling in Drosophila
Abstractp. 205
Introductionp. 206
Genetic Screens: Identification of Network Components and Their Relationshipsp. 206
Identification and Analysis of TOR-Dependent Cellular Functions in Drosophilap. 210
Referencesp. 214
TOR Signaling and Cell Death
Abstractp. 217
Introduction: Overview of the TOR Signaling Pathwayp. 218
Anti-Cell Death Functions of TORp. 220
Cell Death Associated with the Upregulation of TORp. 226
Autophagy Protects Cells from Neurodegenerative Diseasesp. 231
Conclusions and Prospectivesp. 238
Referencesp. 239
Elucidating TOR Signaling in Chlamydomonas reinhardtii
Abstractp. 245
Introductionp. 246
Inhibition of TOR Signaling by Rapamycin in Chlamydomonasp. 247
TOR Complexesp. 249
Control of Autophagy by TORp. 254
Perspectivesp. 257
Acknowledgmentsp. 257
Referencesp. 258
mTORC1 and mTORC2 in Energy Homeostasis
Abstractp. 263
Introductionp. 263
mTORC1 in the Hypothalamusp. 264
mTORC1 in Pancreatic -Cellsp. 267
mTORC1 and mTORC2 in Adipose Tissuep. 268
mTORC1 and mTORC2 in Musclep. 270
mTORC1 in the Liverp. 271
Conclusionp. 273
Acknowledgmentsp. 273
Referencesp. 273
TOR Signaling and Aging
Abstractp. 279
Introductionp. 280
TOR and Aging in S. cerevisiaep. 280
TOR and Aging in C. elegansp. 285
TOR and Aging in Drosophilap. 289
TOR and Aging in Mammalsp. 291
Conclusion and Future Perspectivesp. 293
Acknowledgmentsp. 294
Referencesp. 294
mTOR Signaling and Human Cancer
Abstractp. 301
Introductionp. 302
Frequent Activation of the mTOR Signaling in Human Cancerp. 303
Identification of mTOR Mutations in Human Cancerp. 306
Inhibitors of the mTOR Signalingp. 309
Future Prospectsp. 313
Acknowledgmentp. 314
Referencesp. 314
Systems Biology and TOR: Past, Present, and Future
Abstractp. 317
Introductionp. 318
Genome-Wide Approach to Defining the TOR Networkp. 320
Integration of Datap. 333
Computational Modeling and Predictionp. 336
Future: TOR and Cancerp. 339
Referencesp. 342
Author Indexp. 349
Indexp. 381
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