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

1. II. Introduction 2. III. mTORC1 Targets and Control of Translation 3. IV. Conclusion 4. The TSC1–TSC2 Complex 5. I. Abstract 6. II. Introduction 7. III. Downstream Functions: Regulation of the TOR Complexes by the TSC1–TSC2 Complex 8. IV. Upstream Regulation: The TSC1–TSC2 Complex Integrates Diverse Signals to Regulate mTORC1 9. V. Aberrant Inhibition of the TSC1–TSC2 Complex Leading to Activation of mTORC1 in the Majority of Human Tumors 10. VI. Important Outstanding Questions Concerning the TSC1–TSC2 Complex 11. AMPK Control of mTOR Signaling and Growth 12. I. Abstract 13. II. AMPK is an Energy Sensing Kinase 14. III. mTOR is a Central Conserved Regulator of Growth and Metabolism 15. IV. AMPK Inhibits mTORC1 Through Phosphorylation of TSC2 and Raptor 16. V. AMPK and mTOR Have Opposing Roles in Specialized Metabolic Tissues in Mammals 17. VI. AMPK and TOR Function in Model Organisms to Control Growth, Metabolism, Autophagy, and Aging 18. VII. Therapeutic Implications 19. VIII. Future Perspectives 20. Acknowledgments 21. mTOR Signaling by Amino Acid Nutrients 22. I. Abstract 23. II. Nutrient Signaling to mTOR: Introduction 24. III. The Sensing of Amino Acid Nutrients 25. IV. Amino Acid Transporters and mTOR Signaling 26. V. Evidence That Intracellular Signaling Molecules Relay the Presence of Amino Acid Sufficiency to mTORC1 27. VI. MAP4K3 Participates in Amino Acid Signaling and Maintenance of Cell Size 28. VII. MAP4K3 Promotes Apoptosis via Regulation of the BH3-Only Proteins 29. Acknowledgments 30. mTORC2 31. I. Abstract 32. II. Structure of mTOR Complex 2 (mTORC2) 33. III. Role of mTORC2 34. IV. Regulation of mTORC2 35. V. Potential of mTOR Inhibitors in Cancer Treatment 36. TORC2 and Chemotaxis in Dictyostelium discoideum 37. I. Abstract 38. II. Introduction 39. III. The Life Cycle of D. discoideum 40. IV. The Components of TORC2–PDK–PKB Pathway in D. discoideum 41. V. The Signal Transduction Pathway for Chemotaxis 42. VI. Conclusion 43. Acknowledgments 44. The TOR-Mediated Regulation of Autophagy in the Yeast Saccharomyces cerevisiae 45. I. Abstract 46. II. Autophagy and ATG Genes in Yeast 47. III. Induction of Autophagy by Nutrient Limitation 48. IV. Induction of Autophagy by TOR Inactivation 49. V. Regulation of Atg1 Kinase Complex by TOR Complex1 50. VI. Phosphorylation of Atg13 by TORC1 to Regulate Autophagy 51. VII. ULK Complex: Mammalian Counterpart of Yeast Atg1 Complex 52. VIII. Concluding Remarks 53. Acknowledgments 54. Conservation of the Tsc/Rheb/TORC1/S6K/S6 Signaling in Fission Yeast 55. I. Abstract 56. II. Introduction 57. III. Overview of the TSC/Rheb/TORC1 Signaling in Fission Yeast 58. IV. PAS Assay and Detection of S6 in Fission Yeast 59. V. S6 Kinase in Fission Yeast 60. VI. Regulation of the TORC1 Signaling 61. VII. Effect of Rapamycin on the TORC1 Signaling 62. VIII. Future Prospects 63. Acknowledgments 64. The Systemic Control of Growth, Physiology, and Behavior by TOR Signaling in Drosophila 65. I. Abstract 66. II. Introduction 67. III. Growth Rate 68. IV. Developmental Timing 69. V. Feeding Behavior 70. VI. Fertility 71. VII. Control of Lifespan 72. Cell-Intrinsic Functions and Regulation of TOR Signaling in Drosophila 73. I. Abstract 74. II. Introduction 75. III. Genetic Screens: Identification of Network Components and Their Relationships 76. IV. Identification and Analysis of TOR-Dependent Cellular Functions in Drosophila 77. TOR Signaling and Cell Death 78. I. Abstract 79. II. Introduction: Overview of the TOR Signaling Pathway 80. III. Anti-Cell Death Functions of TOR 81. IV. Cell Death Associated with the Upregulation of TOR 82. V. Autophagy Protects Cells from Neurodegenerative Diseases 83. VI. Conclusions and Prospectives 84. Elucidating TOR Signaling in Chlamydomonas reinhardtii 85. I. Abstract 86. II. Introduction 87. III. Inhibition of TOR Signaling by Rapamycin in Chlamydomonas 88. IV. TOR Complexes 89. V. Control of Autophagy by TOR 90. VI. Perspectives 91. Acknowledgments 92. mTORC1 and mTORC2 in Energy Homeostasis 93. I. Abstract 94. II. Introduction 95. III. mTORC1 in the Hypothalamus 96. IV. mTORC1 in Pancreatic β-Cells 97. V. mTORC1 and mTORC2 in Adipose Tissue 98. VI. mTORC1 and mTORC2 in Muscle 99. VII. mTORC1 in the Liver 100. VIII. Conclusion 101. Acknowledgments 102. TOR Signaling and Aging 103. I. Abstract 104. II. Introduction 105. III. TOR and Aging in S. cerevisiae 106. IV. TOR and Aging in C. elegans 107. V. TOR and Aging in Drosophila 108. VI. TOR and Aging in Mammals 109. VII. Conclusion and Future Perspectives 110. Acknowledgments 111. mTOR Signaling and Human Cancer 112. I. Abstract 113. II. Introduction 114. III. Frequent Activation of the mTOR Signaling in Human Cancer 115. IV. Identification of mTOR Mutations in Human Cancer 116. V. Inhibitors of the mTOR Signaling 117. VI. Future Prospects 118. Acknowledgment 119. Systems Biology and TOR 120. I. Abstract 121. II. Introduction 122. III. Genome-Wide Approach to Defining the TOR Network 123. IV. Integration of Data 124. V. Computational Modeling and Prediction 125. VI. Future: TOR and Cancer