mTOR at the nexus of nutrition, growth, ageing and disease

Repertoires of Autophagy in the Pathogenesis of Ocular Diseases

Li, Y., Jiang, Q. L., Cao, G.-F., Yao, J., & Yan, B. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000373980 · Cited by 16,351

Molecular Mechanisms of Depression: Perspectives on New Treatment Strategies

Lang, U. E., & Borgwardt, S. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350094 · Cited by 8,526

AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1

Kim, J., Kundu, M., Viollet, B., & Guan, K.-L. (2011) · Nature Cell Biology · doi:10.1038/ncb2152 · Cited by 7,227

Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex

Sarbassov, D. D., Guertin, D. A., Ali, S. M., & Sabatini, D. M. (2005) · Science · doi:10.1126/science.1106148 · Cited by 6,216

Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B

Cross, D. A. E., Alessi, D. R., Cohen, P., Andjelkovich, M., & Hemmings, B. A. (1995) · Nature · doi:10.1038/378785a0 · Cited by 5,244

Induction of the Vitamin D Receptor Attenuates Autophagy Dysfunction-Mediated Cell Death Following Traumatic Brain Injury

Cui, C., Cui, J., Jin, F., Cui, Y., Li, R., Jiang, X., Tian, Y., Wang, R. C., Jiang, P., & Gao, J. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000479571 · Cited by 5,214

SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver

Horton, J. D., Goldstein, J. L., & Brown, M. S. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15593 · Cited by 4,794

AMPK: guardian of metabolism and mitochondrial homeostasis

Herzig, S., & Shaw, R. J. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.95 · Cited by 4,192

SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver

Horton, J. D., Goldstein, J. L., & Brown, M. S. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215593 · Cited by 4,092

TSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival

Inoki, K., Zhu, T., & Guan, K.-L. (2003) · Cell · doi:10.1016/s0092-8674(03)00929-2 · Cited by 3,914

Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice

Hara, T., Nakamura, K., Matsui, M., Yamamoto, A., Nakahara, Y., Suzuki-Migishima, R., Yokoyama, M., Mishima, K., Saito, I., Okano, H., et al. (2006) · Nature · doi:10.1038/nature04724 · Cited by 3,882

AMPK Phosphorylation of Raptor Mediates a Metabolic Checkpoint

Gwinn, D. M., Shackelford, D. B., Egan, D. F., Mihaylova, M. M., Mery, A., Vasquez, D. S., Turk, B. E., & Shaw, R. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.03.003 · Cited by 3,849

Rapamycin fed late in life extends lifespan in genetically heterogeneous mice

Harrison, D. E., Strong, R., Sharp, Z. D., Nelson, J. F., Astle, C. M., Flurkey, K., Nadon, N. L., Wilkinson, J. E., Frenkel, K., Carter, C. S., et al. (2009) · Nature · doi:10.1038/nature08221 · Cited by 3,766

Stimulation of adipogenesis in fibroblasts by PPARγ2, a lipid-activated transcription factor

Tontonoz, P., Hu, E., & Spiegelman, B. M. (1994) · Cell · doi:10.1016/0092-8674(94)90006-x · Cited by 3,564

Loss of autophagy in the central nervous system causes neurodegeneration in mice

Komatsu, M., Waguri, S., Chiba, T., Murata, S., Iwata, J.-I., Tanida, I., Ueno, T., Koike, M., Uchiyama, Y., Kominami, E., et al. (2006) · Nature · doi:10.1038/nature04723 · Cited by 3,500

Anorexigenic and Orexigenic Hormone Modulation of Mammalian Target of Rapamycin Complex 1 Activity and the Regulation of Hypothalamic Agouti-Related Protein mRNA Expression

Watterson, K. R., Bestow, D., Gallagher, J. R., Hamilton, D. L., Ashford, F. B., Meakin, P. J., & Ashford, M. L. J. (2012) · Neurosignals · doi:10.1159/000334144 · Cited by 3,395

TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling

Inoki, K., Li, Y., Zhu, T., Wu, J., & Guan, K.-L. (2002) · Nature Cell Biology · doi:10.1038/ncb839 · Cited by 3,083

mTOR Interacts with Raptor to Form a Nutrient-Sensitive Complex that Signals to the Cell Growth Machinery

Kim, D., Sarbassov, D. D., Ali, S. M., King, J. E., Latek, R. R., Erdjument‐Bromage, H., Tempst, P., & Sabatini, D. M. (2002) · Cell · doi:10.1016/s0092-8674(02)00808-5 · Cited by 3,051

mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists

Li, N., Lee, B., Liu, R.-J., Banasr, M., Dwyer, J. M., Iwata, M., Li, X.-Y., Aghajanian, G., & Duman, R. S. (2010) · Science · doi:10.1126/science.1190287 · Cited by 2,881

The role of autophagy during the early neonatal starvation period

Kuma, A., Hatano, M., Matsui, M., Yamamoto, A., Nakaya, H., Yoshimori, T., Ohsumi, Y., Tokuhisa, T., & Mizushima, N. (2004) · Nature · doi:10.1038/nature03029 · Cited by 2,865

The Rag GTPases Bind Raptor and Mediate Amino Acid Signaling to mTORC1

Sancak, Y., Peterson, T. R., Shaul, Y. D., Lindquist, R. A., Thoreen, C. C., Bar-Peled, L., & Sabatini, D. M. (2008) · Science · doi:10.1126/science.1157535 · Cited by 2,773

Mechanism and medical implications of mammalian autophagy

Dikic, I., & Elazar, Z. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0003-4 · Cited by 2,771

Rictor, a Novel Binding Partner of mTOR, Defines a Rapamycin-Insensitive and Raptor-Independent Pathway that Regulates the Cytoskeleton

Sarbassov, D. D., Ali, S. M., Kim, D.-H., Guertin, D. A., Latek, R. R., Erdjument-Bromage, H., Tempst, P., & Sabatini, D. M. (2004) · Current Biology · doi:10.1016/j.cub.2004.06.054 · Cited by 2,665

Ragulator-Rag Complex Targets mTORC1 to the Lysosomal Surface and Is Necessary for Its Activation by Amino Acids

Sancak, Y., Bar-Peled, L., Zoncu, R., Markhard, A. L., Nada, S., & Sabatini, D. M. (2010) · Cell · doi:10.1016/j.cell.2010.02.024 · Cited by 2,464

Prolonged Rapamycin Treatment Inhibits mTORC2 Assembly and Akt/PKB

Sarbassov, D. D., Ali, S. M., Sengupta, S., Sheen, J.-H., Hsu, P. P., Bagley, A. F., Markhard, A. L., & Sabatini, D. M. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.03.029 · Cited by 2,365

Impairment of starvation-induced and constitutive autophagy in Atg7 -deficient mice

Komatsu, M., Waguri, S., Ueno, T., Iwata, J., Murata, S., Tanida, I., Ezaki, J., Mizushima, N., Ohsumi, Y., Uchiyama, Y., et al. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200412022 · Cited by 2,331

Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive

Jacinto, E., Loewith, R., Schmidt, A., Lin, S., Rüegg, M. A., Hall, A., & Hall, M. N. (2004) · Nature Cell Biology · doi:10.1038/ncb1183 · Cited by 2,097

Nutrient-dependent mTORC1 Association with the ULK1–Atg13–FIP200 Complex Required for Autophagy

Hosokawa, N., Hara, T., Kaizuka, T., Kishi, C., Takamura, A., Miura, Y., Iemura, S.-I., Natsume, T., Takehana, K., Yamada, N., et al. (2009) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-12-1248 · Cited by 2,076

The role of autophagy in neurodegenerative disease

Nixon, R. A. (2013) · Nature Medicine · doi:10.1038/nm.3232 · Cited by 2,059

A mammalian protein targeted by G1-arresting rapamycin–receptor complex

Brown, E. J., Albers, M. W., Bum Shin, T., ichikawa, K., Keith, C. T., Lane, W. S., & Schreiber, S. L. (1994) · Nature · doi:10.1038/369756a0 · Cited by 2,053

Activation of a metabolic gene regulatory network downstream of mTOR complex 1

Düvel, K., Yecies, J. L., Menon, S., Raman, P., Lipovsky, A. I., Souza, A. L., Triantafellow, E., Ma, Q., Gorski, R., Cleaver, S., et al. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.06.022 · Cited by 2,020

Targets for Cell Cycle Arrest by the Immunosuppressant Rapamycin in Yeast

Heitman, J., Movva, N. R., & Hall, M. N. (1991) · Science · doi:10.1126/science.1715094 · Cited by 2,010

NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses

Autry, A. E., Adachi, M., Nosyreva, E., Na, E. S., Los, M. F., Cheng, P.-F., Kavalali, E. T., & Monteggia, L. M. (2011) · Nature · doi:10.1038/nature10130 · Cited by 1,926

A lysosome‐to‐nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB

Settembre, C., Zoncu, R., Medina, D. L., Vetrini, F., Erdin, S., Erdin, S., Huynh, T., Ferron, M., Karsenty, G., Vellard, M. C., et al. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.32 · Cited by 1,920

Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling

Inoki, K., Li, Y., Xu, T., & Guan, K.-L. (2003) · Genes & Development · doi:10.1101/gad.1110003 · Cited by 1,911

Raptor, a Binding Partner of Target of Rapamycin (TOR), Mediates TOR Action

Hara, K., Maruki, Y., Long, X., Yoshino, K.-I., Oshiro, N., Sujuti, H., Tokunaga, C., Avruch, J., & Yonezawa, K. (2002) · Cell · doi:10.1016/s0092-8674(02)00833-4 · Cited by 1,810

An ATP-competitive Mammalian Target of Rapamycin Inhibitor Reveals Rapamycin-resistant Functions of mTORC1

Thoreen, C. C., Kang, S. A., Chang, J. W., Liu, Q., Zhang, J., Gao, Y., Reichling, L. J., Sim, T., Sabatini, D. M., & Gray, N. S. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m900301200 · Cited by 1,803

Rapamycin (AY-22,989), a new antifungal antibiotic. I. Taxonomy of the producing streptomycete and isolation of the active principle.

Vézina, C., KUDELSKI, A., & Sehgal, S. N. (1975) · The Journal of Antibiotics · doi:10.7164/antibiotics.28.721 · Cited by 1,691

Promoting Axon Regeneration in the Adult CNS by Modulation of the PTEN/mTOR Pathway

Park, K. K., Liu, K., Hu, Y., Smith, P. D., Wang, C., Cai, B., Xu, B., Connolly, L., Kramvis, I., Sahin, M., et al. (2008) · Science · doi:10.1126/science.1161566 · Cited by 1,686

Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity

Um, S. H., Frigerio, F., Watanabe, M., Picard, F., Joaquin, M., Sticker, M., Fumagalli, S., Allegrini, P. R., Kozma, S. C., Auwerx, J., et al. (2004) · Nature · doi:10.1038/nature02866 · Cited by 1,677

mTORC1 Senses Lysosomal Amino Acids Through an Inside-Out Mechanism That Requires the Vacuolar H + -ATPase

Zoncu, R., Bar-Peled, L., Efeyan, A., Wang, S., Sancak, Y., & Sabatini, D. M. (2011) · Science · doi:10.1126/science.1207056 · Cited by 1,673

Extensive Involvement of Autophagy in Alzheimer Disease: An Immuno-Electron Microscopy Study

Nixon, R. A., Wegiel, J., Kumar, A., Yu, W. H., Peterhoff, C., Cataldo, A., & Cuervo, A. M. (2005) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/64.2.113 · Cited by 1,588

Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway

Manning, B. D., Tee, A. R., Logsdon, M. N., Blenis, J., & Cantley, L. C. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00568-3 · Cited by 1,555

Termination of autophagy and reformation of lysosomes regulated by mTOR

Yu, L., McPhee, C. K., Zheng, L., Mardones, G. A., Rong, Y., Peng, J., Mi, N., Zhao, Y., Liu, Z., Wan, F., et al. (2010) · Nature · doi:10.1038/nature09076 · Cited by 1,544

De novo mutations in epileptic encephalopathies

Epi4K Consortium, & Epilepsy Phenome/Genome Project (2013) · Nature · doi:10.1038/nature12439 · Cited by 1,514

RAFT1: A mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs

Sabatini, D. M., Erdjument-Bromage, H., Lui, M., Tempst, P., & Snyder, S. H. (1994) · Cell · doi:10.1016/0092-8674(94)90570-3 · Cited by 1,509

mTOR controls mitochondrial oxidative function through a YY1–PGC-1α transcriptional complex

Cunningham, J. T., Rodgers, J. T., Arlow, D. H., Vazquez, F., Mootha, V. K., & Puigserver, P. (2007) · Nature · doi:10.1038/nature06322 · Cited by 1,488

Insulin-regulated hepatic gluconeogenesis through FOXO1–PGC-1α interaction

Puigserver, P., Rhee, J., Donovan, J., Walkey, C. J., Yoon, J. C., Oriente, F., Kitamura, Y., Altomonte, J., Dong, H., Accili, D., et al. (2003) · Nature · doi:10.1038/nature01667 · Cited by 1,487

A unifying model for mTORC1-mediated regulation of mRNA translation

Thoreen, C. C., Chantranupong, L., Keys, H. R., Wang, T., Gray, N. S., & Sabatini, D. M. (2012) · Nature · doi:10.1038/nature11083 · Cited by 1,477

Ablation in Mice of the mTORC Components raptor, rictor, or mLST8 Reveals that mTORC2 Is Required for Signaling to Akt-FOXO and PKCα, but Not S6K1

Guertin, D. A., Stevens, D. M., Thoreen, C. C., Burds, A. A., Kalaany, N. Y., Moffat, J., Brown, M., Fitzgerald, K. J., & Sabatini, D. M. (2006) · Developmental Cell · doi:10.1016/j.devcel.2006.10.007 · Cited by 1,467

ULK1·ATG13·FIP200 Complex Mediates mTOR Signaling and Is Essential for Autophagy

Ganley, I. G., Lam, D. H., Wang, J., Ding, X., Chen, S., & Jiang, X. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m900573200 · Cited by 1,447

SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth

Porstmann, T., Santos, C. R., Griffiths, B., Cully, M., Wu, M., Leevers, S., Griffiths, J. R., Chung, Y.-L., & Schulze, A. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.07.007 · Cited by 1,413

SIN1/MIP1 Maintains rictor-mTOR Complex Integrity and Regulates Akt Phosphorylation and Substrate Specificity

Jacinto, E., Facchinetti, V., Liu, D., Soto, N., Wei, S., Jung, S. Y., Huang, Q., Qin, J., & Su, B. (2006) · Cell · doi:10.1016/j.cell.2006.08.033 · Cited by 1,407

The Transcription Factor TFEB Links mTORC1 Signaling to Transcriptional Control of Lysosome Homeostasis

Roczniak-Ferguson, A., Petit, C. S. V., Froehlich, F., Qian, S., Ky, J., Angarola, B. L., Walther, T. C., & Ferguson, S. M. (2012) · Science Signaling · doi:10.1126/scisignal.2002790 · Cited by 1,393

Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex

Brugarolas, J., Lei, K., Hurley, R. L., Manning, B. D., Reiling, J. H., Hafen, E., Witters, L. A., Ellisen, L. W., & Kaelin, W. G. (2004) · Genes & Development · doi:10.1101/gad.1256804 · Cited by 1,384

TSC2 Integrates Wnt and Energy Signals via a Coordinated Phosphorylation by AMPK and GSK3 to Regulate Cell Growth

Inoki, K., Ouyang, H., Zhu, T., Lindvall, C., Wang, Y., Zhang, X., Yang, Q., Bennett, C., Harada, Y., Stankunas, K., et al. (2006) · Cell · doi:10.1016/j.cell.2006.06.055 · Cited by 1,377

Amino Acid Sufficiency and mTOR Regulate p70 S6 Kinase and eIF-4E BP1 through a Common Effector Mechanism

Hara, K., Yonezawa, K., Weng, Q.-P., Kozlowski, M. T., BELHAM, C. M., & Avruch, J. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.23.14484 · Cited by 1,370

Regulation of TORC1 by Rag GTPases in nutrient response

Kim, E., Goraksha-Hicks, P., Li, L., Neufeld, T. P., & Guan, K.-L. (2008) · Nature Cell Biology · doi:10.1038/ncb1753 · Cited by 1,349

Regulation of 4E-BP1 phosphorylation: a novel two-step mechanismPreprint

Gingras, A., Gygi, S. P., Raught, B., Polakiewicz, R. D., Abraham, R. T., Hoekstra, M. F., Aebersold, R. H., & Sonenberg, N. (1999) · Genes & Development · doi:10.1101/gad.13.11.1422 · Cited by 1,348

MTORC1 functions as a transcriptional regulator of autophagy by preventing nuclear transport of TFEB

Martina, J. A., Chen, Y., Gucek, M., & Puertollano, R. (2012) · Autophagy · doi:10.4161/auto.19653 · Cited by 1,333

The translational landscape of mTOR signalling steers cancer initiation and metastasis

Hsieh, A. C., Liu, Y., Edlind, M. P., Ingolia, N. T., Janes, M. R., Sher, A., Shi, E. Y., Stumpf, C. R., Christensen, C., Bonham, M. J., et al. (2012) · Nature · doi:10.1038/nature10912 · Cited by 1,313

Sestrin2 is a leucine sensor for the mTORC1 pathway

Wolfson, R. L., Chantranupong, L., Saxton, R. A., Shen, K., Scaria, S. M., Cantor, J. R., & Sabatini, D. M. (2016) · Science · doi:10.1126/science.aab2674 · Cited by 1,306

Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway

Kapahi, P., Zid, B. M., Harper, T., Koslover, D., Sapin, V., & Benzer, S. (2004) · Current Biology · doi:10.1016/j.cub.2004.03.059 · Cited by 1,293

Regulation of Yeast Replicative Life Span by TOR and Sch9 in Response to Nutrients

Kaeberlein, M., Powers, R. W., Steffen, K. K., Westman, E. A., Hu, D., Dang, N., Kerr, E. O., Kirkland, K. T., Fields, S., & Kennedy, B. K. (2005) · Science · doi:10.1126/science.1115535 · Cited by 1,293

mTOR Complex 1 Regulates Lipin 1 Localization to Control the SREBP Pathway

Peterson, T. R., Sengupta, S., Harris, T. E., Carmack, A. E., Kang, S. A., Balderas, E., Guertin, D. A., Madden, K. L., Carpenter, A. E., Finck, B. N., et al. (2011) · Cell · doi:10.1016/j.cell.2011.06.034 · Cited by 1,293

Phosphorylation and Functional Inactivation of TSC2 by Erk

Ma, L., Chen, Z., Erdjument-Bromage, H., Tempst, P., & Pandolfi, P. P. (2005) · Cell · doi:10.1016/j.cell.2005.02.031 · Cited by 1,268

mTOR and S6K1 Mediate Assembly of the Translation Preinitiation Complex through Dynamic Protein Interchange and Ordered Phosphorylation Events

Holz, M. K., Ballif, B. A., Gygi, S. P., & Blenis, J. (2005) · Cell · doi:10.1016/j.cell.2005.10.024 · Cited by 1,262

PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase

Sancak, Y., Thoreen, C. C., Peterson, T. R., Lindquist, R. A., Kang, S. A., Spooner, E., Carr, S. A., & Sabatini, D. M. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.03.003 · Cited by 1,236

Insulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40

Haar, E. V., Lee, S.-I., Bandhakavi, S., Griffin, T. J., & Kim, D. (2007) · Nature Cell Biology · doi:10.1038/ncb1547 · Cited by 1,227

DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival

Peterson, T. R., Laplante, M., Thoreen, C. C., Sancak, Y., Kang, S. A., Kuehl, W. M., Gray, N. S., & Sabatini, D. M. (2009) · Cell · doi:10.1016/j.cell.2009.03.046 · Cited by 1,202

Rapamycin-Induced Insulin Resistance Is Mediated by mTORC2 Loss and Uncoupled from Longevity

Lamming, D. W., Ye, L., Katajisto, P., Goncalves, M. D., Saitoh, M., Stevens, D. M., Davis, J. G., Salmon, A. B., Richardson, A., Ahima, R. S., et al. (2012) · Science · doi:10.1126/science.1215135 · Cited by 1,199

MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation

Laberge, R.-M., Sun, Y., Orjalo, A. V., Patil, C. K., Freund, A., Zhou, L., Curran, S. C., Davalos, A. R., Wilson-Edell, K. A., Liu, S., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3195 · Cited by 1,160

Rapamycin-FKBP specifically blocks growth-dependent activation of and signaling by the 70 kd S6 protein kinases

Chung, J., Kuo, C. J., Crabtree, G. R., & Blenis, J. (1992) · Cell · doi:10.1016/0092-8674(92)90643-q · Cited by 1,151

Loss of mTOR-Dependent Macroautophagy Causes Autistic-like Synaptic Pruning Deficits

Tang, G., Gudsnuk, K., Kuo, S.-H., Cotrina, M. L., Rosoklija, G., Sosunov, A., Sonders, M. S., Kanter, E., Castagna, C., Yamamoto, A., et al. (2014) · Neuron · doi:10.1016/j.neuron.2014.07.040 · Cited by 1,146

RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1

Burnett, P. E., Barrow, R. K., Cohen, N. A., Snyder, S. H., & Sabatini, D. M. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.4.1432 · Cited by 1,130

The TSC1-2 tumor suppressor controls insulin–PI3K signaling via regulation of IRS proteins

Harrington, L. S., Findlay, G. M., Gray, A., Толкачева, Т. А., Wigfield, S., Rebholz, H., Barnett, J., Leslie, N. R., Cheng, S., Shepherd, P. R., et al. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200403069 · Cited by 1,123

Ribosomal Protein S6 Kinase 1 Signaling Regulates Mammalian Life Span

Selman, C., Tullet, J. M. A., Wieser, D., Irvine, E., Lingard, S. J., Choudhury, A. I., Claret, M., Al-Qassab, H., Carmignac, D., Ramadani, F., et al. (2009) · Science · doi:10.1126/science.1177221 · Cited by 1,120

Active-Site Inhibitors of mTOR Target Rapamycin-Resistant Outputs of mTORC1 and mTORC2

Feldman, M. E., Apsel, B., Uotila, A., Loewith, R., Knight, Z. A., Ruggero, D., & Shokat, K. M. (2009) · PLoS Biology · doi:10.1371/journal.pbio.1000038 · Cited by 1,111

The LKB1 tumor suppressor negatively regulates mTOR signaling

Shaw, R. J., Bardeesy, N. M., Manning, B. D., Lopez, L. V., Kosmatka, M., DePinho, R. A., & Cantley, L. C. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.06.007 · Cited by 1,107

The mTOR‐regulated phosphoproteome reveals a mechanism of mTORC1‐mediated inhibition of growth factor signaling

Hsu, P. P., Kang, S. A., Rameseder, J., Zhang, Y., Ottina, K. A., Lim, D., Peterson, T. R., Choi, Y., Gray, N. S., Yaffe, M. B., et al. (2011) · Science · doi:10.1126/science.1199498 · Cited by 1,084

A Tumor Suppressor Complex with GAP Activity for the Rag GTPases That Signal Amino Acid Sufficiency to mTORC1

Bar-Peled, L., Chantranupong, L., Cherniack, A. D., Chen, W. W., Ottina, K. A., Grabiner, B. C., Spear, E. D., Carter, S. L., Meyerson, M., & Sabatini, D. M. (2013) · Science · doi:10.1126/science.1232044 · Cited by 1,080

Tuberous Sclerosis Complex Gene Products, Tuberin and Hamartin, Control mTOR Signaling by Acting as a GTPase-Activating Protein Complex toward Rheb

Tee, A. R., Manning, B. D., Roux, P. P., Cantley, L. C., & Blenis, J. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00506-2 · Cited by 1,080

mTOR kinase structure, mechanism and regulation

Yang, H., Rudge, D. G., Koos, J. D., Vaidialingam, B., Yang, H. J., & Pavletich, N. P. (2013) · Nature · doi:10.1038/nature12122 · Cited by 1,075

Influence of TOR kinase on lifespan in C. elegans

Vellai, T., Takacs-Vellai, K., Zhang, Y., Kovacs, A. L., Orosz, L., & Müller, F. (2003) · Nature · doi:10.1038/426620a · Cited by 1,057

Mechanisms of Life Span Extension by Rapamycin in the Fruit Fly Drosophila Melanogaster

Bjedov, I., Toivonen, J. M., Kerr, F., Slack, C., Jacobson, J., Foley, A., & Partridge, L. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2009.11.010 · Cited by 1,057

Insulin Activation of Rheb, a Mediator of mTOR/S6K/4E-BP Signaling, Is Inhibited by TSC1 and 2

Garami, A., Zwartkruis, F. J. T., Nobukuni, T., Joaquin, M., Roccio, M., Stocker, H., Kozma, S. C., Hafen, E., Bos, J. L., & Thomas, G. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00220-x · Cited by 1,043

Rheb Binds and Regulates the mTOR Kinase

Long, X., Lin, Y., Ortiz-Vega, S., Yonezawa, K., & Avruch, J. (2005) · Current Biology · doi:10.1016/j.cub.2005.02.053 · Cited by 1,005

GβL, a Positive Regulator of the Rapamycin-Sensitive Pathway Required for the Nutrient-Sensitive Interaction between Raptor and mTOR

Kim, D., Sarbassov, D. D., Ali, S. M., Latek, R. R., Guntur, K., Erdjument‐Bromage, H., Tempst, P., & Sabatini, D. M. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00114-x · Cited by 992

Extension of Chronological Life Span in Yeast by Decreased TOR Pathway Signaling

Powers, R. W., Kaeberlein, M., Caldwell, S. D., Kennedy, B. K., & Fields, S. (2006) · Genes & Development · doi:10.1101/gad.1381406 · Cited by 982

Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Birt-Hogg-Dubé syndrome

Nickerson, M. L., Warren, M. B., Toro, J. R., Matrosova, V. Y., Glenn, G. M., Turner, M. L. C., Duray, P. H., Merino, M. J., Choyke, P. L., Pavlovich, C. P., et al. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00104-6 · Cited by 940

A hierarchy of ATP-consuming processes in mammalian cells

Buttgereit, F., & Brand, M. D. (1995) · Biochemical Journal · doi:10.1042/bj3120163 · Cited by 939

Ragulator Is a GEF for the Rag GTPases that Signal Amino Acid Levels to mTORC1

Bar-Peled, L., Schweitzer, L. D., Zoncu, R., & Sabatini, D. M. (2012) · Cell · doi:10.1016/j.cell.2012.07.032 · Cited by 918

mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1)

García-Martínez, J. M., & Alessi, D. R. (2008) · Biochemical Journal · doi:10.1042/bj20081668 · Cited by 907

Lysosomal positioning coordinates cellular nutrient responses

Korolchuk, V. I., Saiki, S., Lichtenberg, M., Siddiqi, F. H., Roberts, E. A., Imarisio, S., Jahreiss, L., Sarkar, S., Futter, M., Menzies, F. M., et al. (2011) · Nature Cell Biology · doi:10.1038/ncb2204 · Cited by 891

Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner

Kalender, A., Selvaraj, A., Kim, S. Y., Gulati, P., Brûlé, S., Viollet, B., Kemp, B. E., Bardeesy, N., Dennis, P., Schlager, J. J., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.03.014 · Cited by 889

Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice

Tsai, P. T., Hull, C., Chu, Y., Greene-Colozzi, E., Sadowski, A. R., Leech, J. M., Steinberg, J., Crawley, J. N., Regehr, W. G., & Sahin, M. (2012) · Nature · doi:10.1038/nature11310 · Cited by 888

Isolation of a Protein Target of the FKBP12-Rapamycin Complex in Mammalian Cells

Sabers, C. J., Martin, M. M., Brunn, G. J., Williams, J. M., Dumont, F. J., Wiederrecht, G., & Abraham, R. T. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.2.815 · Cited by 887

Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1

Wang, S., Tsun, Z.-Y., Wolfson, R. L., Shen, K., Wyant, G. A., Plovanich, M., Yuan, E. D., Jones, T. D., Chantranupong, L., Comb, W. C., et al. (2015) · Science · doi:10.1126/science.1257132 · Cited by 865

Phosphoproteomic Analysis Identifies Grb10 as an mTORC1 Substrate That Negatively Regulates Insulin Signaling

Yu, Y., Yoon, S.-O., Poulogiannis, G., Yang, Q., Ma, X. M., Villén, J., Kubica, N., Hoffman, G. R., Cantley, L. C., Gygi, S. P., et al. (2011) · Science · doi:10.1126/science.1199484 · Cited by 864

Phosphorylation of the Translational Repressor PHAS-I by the Mammalian Target of Rapamycin

Brunn, G. J., Hudson, C. C., Sekulić, A., Williams, J. M., Hosoi, H., Houghton, P. J., Lawrence, J. C., & Abraham, R. T. (1997) · Science · doi:10.1126/science.277.5322.99 · Cited by 846

The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway

Chantranupong, L., Scaria, S. M., Saxton, R. A., Gygi, M. P., Shen, K., Wyant, G. A., Wang, T., Harper, J. W., Gygi, S. P., & Sabatini, D. M. (2016) · Cell · doi:10.1016/j.cell.2016.02.035 · Cited by 843

Target of rapamycin in yeast, TOR2, is an essential phosphatidylinositol kinase homolog required for G1 progression

Kunz, J., Henríquez, R., Schneider, U., Deuter‐Reinhard, M., Movva, N. R., & Hall, M. N. (1993) · Cell · doi:10.1016/0092-8674(93)90144-f · Cited by 838

Rapamycin differentially inhibits S6Ks and 4E-BP1 to mediate cell-type-specific repression of mRNA translation

Choo, A. Y., Yoon, S.-O., Kim, S. G., Roux, P. P., & Blenis, J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0809136105 · Cited by 829

Phosphorylation and Activation of p70 s6k by PDK1

Pullen, N., Dennis, P. B., Andjelkovic, M., Dufner, A., Kozma, S. C., Hemmings, B. A., & Thomas, G. (1998) · Science · doi:10.1126/science.279.5351.707 · Cited by 826

Pathogenic Lysosomal Depletion in Parkinson's Disease

Dehay, B., Bové, J., Rodríguez-Muela, N., Perier, C., Recasens, A., Boya, P., & Vila, M. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.1920-10.2010 · Cited by 825

Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans

Hansen, M., Taubert, S., Crawford, D., Libina, N., Lee, S., & Kenyon, C. (2007) · Aging Cell · doi:10.1111/j.1474-9726.2006.00267.x · Cited by 803

Inappropriate Activation of the TSC/Rheb/mTOR/S6K Cassette Induces IRS1/2 Depletion, Insulin Resistance, and Cell Survival Deficiencies

Shah, O. J., Wang, Z., & Hunter, T. R. (2004) · Current Biology · doi:10.1016/j.cub.2004.08.026 · Cited by 800

Transcriptional control of autophagy-lysosome function drives pancreatic cancer metabolism

Perera, R. M., Stoykova, S., Nicolay, B. N., Ross, K. N., Fitamant, J., Boukhali, M., Lengrand, J., Deshpande, V., Selig, M. K., Ferrone, C. R., et al. (2015) · Nature · doi:10.1038/nature14587 · Cited by 799

mTORC1 induces purine synthesis through control of the mitochondrial tetrahydrofolate cycle

Ben-Sahra, I., Hoxhaj, G., Ricoult, S. J. H., Asara, J. M., & Manning, B. D. (2016) · Science · doi:10.1126/science.aad0489 · Cited by 795

mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype

Herranz, N., Gallage, S., Mellone, M., Wuestefeld, T., Klotz, S., Hanley, C. J., Raguz, S., Acosta, J. C., Innes, A. J., Banito, A., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3225 · Cited by 788

Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila

Grandison, R. C., Piper, M. D. W., & Partridge, L. (2009) · Nature · doi:10.1038/nature08619 · Cited by 785

The Neurology of mTOR

Lipton, J. O., & Şahin, M. (2014) · Neuron · doi:10.1016/j.neuron.2014.09.034 · Cited by 771

A Role for Autophagy in the Extension of Lifespan by Dietary Restriction in C. elegans

Hansen, M., Chandra, A., Mitic, L. L., Onken, B., Driscoll, M., & Kenyon, C. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.0040024 · Cited by 766

Spatial Control of the TSC Complex Integrates Insulin and Nutrient Regulation of mTORC1 at the Lysosome

Menon, S., Dibble, C. C., Talbott, G., Hoxhaj, G., Valvezan, A. J., Takahashi, H., Cantley, L. C., & Manning, B. D. (2014) · Cell · doi:10.1016/j.cell.2013.11.049 · Cited by 766

S6K1 −/− / S6K2 −/− Mice Exhibit Perinatal Lethality and Rapamycin-Sensitive 5′-Terminal Oligopyrimidine mRNA Translation and Reveal a Mitogen-Activated Protein Kinase-Dependent S6 Kinase Pathway

Pende, M., Um, S. H., Mieulet, V., Sticker, M., Goss, V. L., Mestan, J., Mueller, M., Fumagalli, S., Kozma, S. C., & Thomas, G. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.8.3112-3124.2004 · Cited by 766

Differential regulation of mTORC1 by leucine and glutamine

Jewell, J. L., Kim, Y. C., Russell, R. C., Yu, F.-X., Park, H. W., Plouffe, S. W., Tagliabracci, V. S., & Guan, K.-L. (2015) · Science · doi:10.1126/science.1259472 · Cited by 757

Autophagy as a promoter of longevity: insights from model organisms

Hansen, M., Rubinsztein, D. C., & Walker, D. W. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0033-y · Cited by 754

mTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake

Yilmaz, Ö. H., Katajisto, P., Lamming, D. W., Gültekin, Y., Bauer-Rowe, K. E., Sengupta, S., Birsoy, K., Dursun, A., Yilmaz, V. O., Selig, M., et al. (2012) · Nature · doi:10.1038/nature11163 · Cited by 753

Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase

Roux, P. P., Ballif, B. A., Anjum, R., Gygi, S. P., & Blenis, J. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405659101 · Cited by 750

Signal integration by mTORC1 coordinates nutrient input with biosynthetic output

Dibble, C. C., & Manning, B. D. (2013) · Nature Cell Biology · doi:10.1038/ncb2763 · Cited by 743

Stimulation of de novo pyrimidine synthesis by growth signaling through mTOR and S6K1

Ben-Sahra, I., Howell, J. J., Asara, J. M., & Manning, B. D. (2013) · Science · doi:10.1126/science.1228792 · Cited by 739

Mature ribosomes are selectively degraded upon starvation by an autophagy pathway requiring the Ubp3p/Bre5p ubiquitin protease

Kraft, C., Deplazes, A., Sohrmann, M., & Peter, M. (2008) · Nature Cell Biology · doi:10.1038/ncb1723 · Cited by 733

S6K1- and ßTRCP-Mediated Degradation of PDCD4 Promotes Protein Translation and Cell Growth

Dorrello, N. V., Peschiaroli, A., Guardavaccaro, D., Colburn, N. H., Sherman, N. E., & Pagano, M. (2006) · Science · doi:10.1126/science.1130276 · Cited by 731

Hypoxia regulates TSC1/2–mTOR signaling and tumor suppression through REDD1-mediated 14–3–3 shuttling

DeYoung, M. P., Horak, P., Sofer, A., Sgroi, D., & Ellisen, L. W. (2008) · Genes & Development · doi:10.1101/gad.1617608 · Cited by 710

Two distinct signal transmission pathways in T lymphocytes are inhibited by complexes formed between an immunophilin and either FK506 or rapamycin.

Bierer, B. E., Mattila, P. S., Standaert, R. F., Herzenberg, L. A., Burakoff, S. J., Crabtree, G. R., & Schreiber, S. L. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.23.9231 · Cited by 706

mSin1 Is Necessary for Akt/PKB Phosphorylation, and Its Isoforms Define Three Distinct mTORC2s

Frías, M. A., Thoreen, C. C., Jaffe, J. D., Schroder, W. A., Sculley, T. B., Carr, S. A., & Sabatini, D. M. (2006) · Current Biology · doi:10.1016/j.cub.2006.08.001 · Cited by 690

Phosphorylation of ribosomal protein S6 is inhibitory for autophagy in isolated rat hepatocytes

Blommaart, E. F. C., Luiken, J. J. F. P., Blommaart, P. J. E., van Woerkom, G. M., & Meijer, A. J. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.5.2320 · Cited by 686

mTOR Regulation and Therapeutic Rejuvenation of Aging Hematopoietic Stem Cells

Chen, C., Liu, Y., Liu, Y., & Zheng, P. (2009) · Science Signaling · doi:10.1126/scisignal.2000559 · Cited by 680

The Mammalian Target of Rapamycin (mTOR) Partner, Raptor, Binds the mTOR Substrates p70 S6 Kinase and 4E-BP1 through Their TOR Signaling (TOS) Motif

Nojima, H., Tokunaga, C., Eguchi, S., Oshiro, N., Sujuti, H., Yoshino, K., Hara, K., Tanaka, N., Avruch, J., & Yonezawa, K. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.c200665200 · Cited by 678

SLC38A9 is a component of the lysosomal amino acid sensing machinery that controls mTORC1

Rebsamen, M., Pochini, L., Stasyk, T., de Araújo, M. E. G., Galluccio, M., Kandasamy, R. K., Snijder, B., Fauster, A., Rudashevskaya, E. L., Bruckner, M., et al. (2015) · Nature · doi:10.1038/nature14107 · Cited by 673

Cowden Syndrome and the PTEN Hamartoma Tumor Syndrome: Systematic Review and Revised Diagnostic Criteria

Pilarski, R., Burt, R., Kohlman, W., Pho, L. N., Shannon, K. M., & Swisher, E. (2013) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djt277 · Cited by 671

Ribosomal protein S6 phosphorylation is a determinant of cell size and glucose homeostasisPreprint

Ruvinsky, I., Sharon, N., Lerer, T., Cohen, H., Stolovich-Rain, M., Nir, T., Dor, Y., Zisman, P., & Meyuhas, O. (2005) · Genes & Development · doi:10.1101/gad.351605 · Cited by 668

FOXO transcription factors: key regulators of cellular quality control

Webb, A. E., & Brunet, A. (2014) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2014.02.003 · Cited by 649

TOR Signaling and Rapamycin Influence Longevity by Regulating SKN-1/Nrf and DAF-16/FoxO

Robida-Stubbs, S., Glover-Cutter, K., Lamming, D. W., Mizunuma, M., Narasimhan, S. D., Neumann-Haefelin, E., Sabatini, D. M., & Blackwell, T. K. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.007 · Cited by 648

mTORC1 controls fasting-induced ketogenesis and its modulation by ageing

Sengupta, S., Peterson, T. R., Laplante, M., Oh, S., & Sabatini, D. M. (2010) · Nature · doi:10.1038/nature09584 · Cited by 646

IKKβ Suppression of TSC1 Links Inflammation and Tumor Angiogenesis via the mTOR Pathway

Lee, D., Kuo, H.-P., Chen, C., Hsu, J.-M., Chou, C., Wei, Y., Sun, H., Li, L., Ping, B., Huang, W., et al. (2007) · Cell · doi:10.1016/j.cell.2007.05.058 · Cited by 639

The Regulation of AMPK β1, TSC2, and PTEN Expression by p53: Stress, Cell and Tissue Specificity, and the Role of These Gene Products in Modulating the IGF-1-AKT-mTOR Pathways

Feng, Z., Hu, W., de Stanchina, E., Teresky, A. K., Jin, S., Lowe, S., & Levine, A. J. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-4149 · Cited by 633

Disruption of the beclin 1–BCL2 autophagy regulatory complex promotes longevity in mice

Fernández, Á. F., Sebti, S., Wei, Y., Zou, Z., Shi, M., McMillan, K. L., He, C., Ting, T., Liu, Y., Chiang, W.-C., et al. (2018) · Nature · doi:10.1038/s41586-018-0162-7 · Cited by 630

The TOR pathway interacts with the insulin signaling pathway to regulate C. elegans larval development, metabolism and life span

Jia, K., Chen, D., & Riddle, D. L. (2004) · Development · doi:10.1242/dev.01255 · Cited by 615

TBC1D7 Is a Third Subunit of the TSC1-TSC2 Complex Upstream of mTORC1

Dibble, C. C., Elis, W., Menon, S., Qin, W., Klekota, J., Asara, J. M., Finan, P. M., Kwiatkowski, D. J., Murphy, L. O., & Manning, B. D. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.06.009 · Cited by 612

Essential function of TORC2 in PKC and Akt turn motif phosphorylation, maturation and signalling

Ikenoue, T., Inoki, K., Yang, Q., Zhou, X., & Guan, K. (2008) · The EMBO Journal · doi:10.1038/emboj.2008.119 · Cited by 605

SAMTOR is an S -adenosylmethionine sensor for the mTORC1 pathway

Gu, X., Orozco, J. M., Saxton, R. A., Condon, K. J., Liu, G. Y., Krawczyk, P. A., Scaria, S. M., Harper, J. W., Gygi, S. P., & Sabatini, D. M. (2017) · Science · doi:10.1126/science.aao3265 · Cited by 598

Hepatic mTORC2 Activates Glycolysis and Lipogenesis through Akt, Glucokinase, and SREBP1c

Hagiwara, A., Cornu, M., Cybulski, N., Polak, P., Betz, C., Trapani, F., Terracciano, L., Heim, M. H., Rüegg, M. A., & Hall, M. N. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.03.015 · Cited by 585

The Folliculin Tumor Suppressor Is a GAP for the RagC/D GTPases That Signal Amino Acid Levels to mTORC1

Tsun, Z.-Y., Bar-Peled, L., Chantranupong, L., Zoncu, R., Wang, T., Kim, C., Spooner, E., & Sabatini, D. M. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.09.016 · Cited by 565

The Dawn of the Age of Amino Acid Sensors for the mTORC1 Pathway

Wolfson, R. L., & Sabatini, D. M. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.07.001 · Cited by 563

Lysosomal cholesterol activates mTORC1 via an SLC38A9–Niemann-Pick C1 signaling complex

Castellano, B. M., Thelen, A. M., Moldavski, O., Feltes, M., van der Welle, R. E. N., Mydock-McGrane, L., Jiang, X., van Eijkeren, R. J., Davis, O. B., Louie, S. M., et al. (2017) · Science · doi:10.1126/science.aag1417 · Cited by 562

4E-BP Extends Lifespan upon Dietary Restriction by Enhancing Mitochondrial Activity in Drosophila

Zid, B. M., Rogers, A. N., Katewa, S. D., Vargas, M. A., Kolipinski, M., Lu, T. A., Benzer, S., & Kapahi, P. (2009) · Cell · doi:10.1016/j.cell.2009.07.034 · Cited by 548

Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40

Yang, H., Jiang, X., Li, B., Yang, H. J., Miller, M., Yang, A., Dhar, A., & Pavletich, N. P. (2017) · Nature · doi:10.1038/nature25023 · Cited by 548

mTOR-dependent activation of the transcription factor TIF-IA links rRNA synthesis to nutrient availabilityPreprint

Mayer, C., Zhao, J., Yuan, X., & Grummt, I. (2004) · Genes & Development · doi:10.1101/gad.285504 · Cited by 544

TOS Motif-Mediated Raptor Binding Regulates 4E-BP1 Multisite Phosphorylation and Function

Schalm, S. S., Fingar, D. C., Sabatini, D. M., & Blenis, J. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00329-4 · Cited by 528

Quantitative Phosphoproteomics Reveal mTORC1 Activates de Novo Pyrimidine Synthesis

Robitaille, A. M., Christen, S., Shimobayashi, M., Cornu, M., Fava, L. L., Moes, S., Prescianotto-Baschong, C., Sauer, U., Jenoe, P., & Hall, M. N. (2013) · Science · doi:10.1126/science.1228771 · Cited by 525

Regulation of eIF-4E BP1 Phosphorylation by mTOR

Hara, K., Yonezawa, K., Kozlowski, M. T., Sugimoto, T., Andrabi, K. I., Weng, Q.-P., Kasuga, M., Nishimoto, I., & Avruch, J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.42.26457 · Cited by 522

Autism-related deficits via dysregulated eIF4E-dependent translational control

Gkogkas, C. G., Khoutorsky, A., Ran, I., Rampakakis, E., Nevarko, T., Weatherill, D. B., Vasuta, C., Yee, S., Truitt, M., Dallaire, P., et al. (2013) · Nature · doi:10.1038/nature11628 · Cited by 522

Identification of Sin1 as an essential TORC2 component required for complex formation and kinase activityPreprint

Yang, Q., Inoki, K., Ikenoue, T., & Guan, K. (2006) · Genes & Development · doi:10.1101/gad.1461206 · Cited by 521

PIK-Related Kinases: DNA Repair, Recombination, and Cell Cycle Checkpoints

Keith, C. T., & Schreiber, S. L. (1995) · Science · doi:10.1126/science.270.5233.50 · Cited by 521

TORC1 inhibition enhances immune function and reduces infections in the elderly

Mannick, J. B., Morris, M., Hockey, H.-U. P., Roma, G., Beibel, M., Kulmatycki, K., Watkins, M., Shavlakadze, T., Zhou, W., Quinn, D., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aaq1564 · Cited by 496

mTORC1 Activator SLC38A9 Is Required to Efflux Essential Amino Acids from Lysosomes and Use Protein as a Nutrient

Wyant, G. A., Abu-Remaileh, M., Wolfson, R. L., Chen, W. W., Freinkman, E., Danai, L. V., Heiden, M. G. V., & Sabatini, D. M. (2017) · Cell · doi:10.1016/j.cell.2017.09.046 · Cited by 494

mTOR-Dependent Regulation of Ribosomal Gene Transcription Requires S6K1 and Is Mediated by Phosphorylation of the Carboxy-Terminal Activation Domain of the Nucleolar Transcription Factor UBF†

Hannan, K. M., Brandenburger, Y., Jenkins, A., Sharkey, K., Cavanaugh, A. H., Rothblum, L. I., Moss, T., Poortinga, G., McArthur, G. A., Pearson, R. B., et al. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.23.8862-8877.2003 · Cited by 489

Adipose-Specific Knockout of raptor Results in Lean Mice with Enhanced Mitochondrial Respiration

Polak, P., Cybulski, N., Feige, J. N., Auwerx, J., Rüegg, M. A., & Hall, M. N. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.09.003 · Cited by 480

Overcoming mTOR resistance mutations with a new-generation mTOR inhibitor

Rodrik-Outmezguine, V. S., Okaniwa, M., Yao, Z., Novotny, C. J., McWhirter, C., Banaji, A., Won, H., Wong, W., Berger, M., de Stanchina, E., et al. (2016) · Nature · doi:10.1038/nature17963 · Cited by 479

Regulation of Peroxisome Proliferator–Activated Receptor-γ Activity by Mammalian Target of Rapamycin and Amino Acids in Adipogenesis

Kim, J. E., & Chen, J. (2004) · Diabetes · doi:10.2337/diabetes.53.11.2748 · Cited by 478

Dose- and Schedule-Dependent Inhibition of the Mammalian Target of Rapamycin Pathway With Everolimus: A Phase I Tumor Pharmacodynamic Study in Patients With Advanced Solid Tumors

Tabernero, J., Rojo, F., Calvo, E., Burris, H., Judson, I., Hazell, K., Martinelli, E., Cajal, S. R. Y., Jones, S., Vidal, L., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.14.5482 · Cited by 474

Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice

Bitto, A., Ito, T. K., Pineda, V. V., LeTexier, N. J., Huang, H. Z., Sutlief, E., Tung, H., Vizzini, N., Chen, B., Smith, K., et al. (2016) · eLife · doi:10.7554/elife.16351 · Cited by 474

Regulation of mTORC1 by the Rag GTPases is necessary for neonatal autophagy and survival

Efeyan, A., Zoncu, R., Chang, S. H., Gumper, I., Snitkin, H., Wolfson, R. L., Kirak, O., Sabatini, D. M., & Sabatini, D. M. (2012) · Nature · doi:10.1038/nature11745 · Cited by 473

Ku-0063794 is a specific inhibitor of the mammalian target of rapamycin (mTOR)

García‐Martínez, J. M., Moran, J., Clarke, R. G., Gray, A., Cosulich, S. C., Chresta, C. M., & Alessi, D. R. (2009) · Biochemical Journal · doi:10.1042/bj20090489 · Cited by 473

The Sestrins Interact with GATOR2 to Negatively Regulate the Amino-Acid-Sensing Pathway Upstream of mTORC1

Chantranupong, L., Wolfson, R. L., Orozco, J. M., Saxton, R. A., Scaria, S. M., Bar-Peled, L., Spooner, E., Isasa, M., Gygi, S. P., & Sabatini, D. M. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.09.014 · Cited by 466

Inhibition of the immune response by rapamycin, a new antifungal antibiotic

Martel, R. R., Klicius, J., & Galet, S. (1977) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y77-007 · Cited by 464

Identification of Protor as a novel Rictor-binding component of mTOR complex-2

Pearce, L. R., Huang, X., Boudeau, J., Pawłowski, R., Wullschleger, S., Deák, M., Ibrahim, A. F. M., Gourlay, R., Magnuson, M. A., & Alessi, D. R. (2007) · Biochemical Journal · doi:10.1042/bj20070540 · Cited by 462

The utilization of extracellular proteins as nutrients is suppressed by mTORC1

Palm, W., Park, Y., Wright, K., Pavlova, N. N., Tuveson, D. A., & Thompson, C. B. (2015) · Cell · doi:10.1016/j.cell.2015.06.017 · Cited by 457

Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway

Saxton, R. A., Knockenhauer, K. E., Wolfson, R. L., Chantranupong, L., Pacold, M. E., Wang, T., Schwartz, T. U., & Sabatini, D. M. (2016) · Science · doi:10.1126/science.aad2087 · Cited by 457

mTOR Kinase Inhibition Causes Feedback-Dependent Biphasic Regulation of AKT Signaling

Rodrik-Outmezguine, V. S., Chandarlapaty, S., Pagano, N. C., Poulikakos, P. I., Scaltriti, M., Moskatel, E., Baselga, J., Guichard, S., & Rosen, N. (2011) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0085 · Cited by 442

Brain-derived neurotrophic factor induces mammalian target of rapamycin-dependent local activation of translation machinery and protein synthesis in neuronal dendrites

Takei, N., Inamura, N., Kawamura, M., Namba, H., Hara, K., Yonezawa, K., & Nawa, H. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.1427-04.2004 · Cited by 442

Longevity pathways converge on autophagy genes to regulate life span inCaenorhabditis elegans

Tóth, M. L., Sigmond, T., Borsos, É., Barna, J., Erdélyi, P., Takács‐Vellai, K., Orosz, L., Kovács, A., Csikós, G., Sass, M., et al. (2008) · Autophagy · doi:10.4161/auto.5618 · Cited by 429

mTORC1 Phosphorylation Sites Encode Their Sensitivity to Starvation and Rapamycin

Kang, S. A., Pacold, M. E., Cervantes, C., Lim, D., Lou, H. J., Ottina, K. A., Gray, N. S., Turk, B. E., Yaffe, M. B., & Sabatini, D. M. (2013) · Science · doi:10.1126/science.1236566 · Cited by 420

Regulation of TORC1 in Response to Amino Acid Starvation via Lysosomal Recruitment of TSC2

Demetriades, C., Doumpas, N., & Teleman, A. A. (2014) · Cell · doi:10.1016/j.cell.2014.01.024 · Cited by 414

Dynamic Adipocyte Phosphoproteome Reveals that Akt Directly Regulates mTORC2

Humphrey, S. J., Yang, G., Yang, P., Fazakerley, D. J., Stöckli, J., Yang, J. Y. H., & James, D. E. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.04.010 · Cited by 412

Metformin Inhibits Hepatic Mtorc1 Signaling via Dose-Dependent Mechanisms Involving AMPK and the TSC Complex

Howell, J. J., Hellberg, K., Turner, M., Talbott, G., Kolar, M. J., Ross, D. S., Hoxhaj, G., Saghatelian, A., Shaw, R. J., & Manning, B. D. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2016.12.009 · Cited by 408

Protein kinase C and the regulation of the actin cytoskeleton

Larsson, C. (2005) · Cellular Signalling · doi:10.1016/j.cellsig.2005.07.010 · Cited by 397

TOR1 and TOR2 are structurally and functionally similar but not identical phosphatidylinositol kinase homologues in yeast.

Helliwell, S. B., Wagner, P., Kunz, J., Deuter‐Reinhard, M., Henríquez, R., & Hall, M. N. (1994) · Molecular Biology of the Cell · doi:10.1091/mbc.5.1.105 · Cited by 390

Autophagy provides metabolic substrates to maintain energy charge and nucleotide pools in Ras-driven lung cancer cellsPreprint

Guo, J. Y., Teng, X., Laddha, S. V., Ma, S., Nostrand, S. C. V., Yang, Y., Khor, S., Chan, C. S., Rabinowitz, J. D., & White, E. (2016) · Genes & Development · doi:10.1101/gad.283416.116 · Cited by 382

Mutations in DEPDC5 cause familial focal epilepsy with variable foci

Dibbens, L. M., de Vries, B., Donatello, S., Heron, S. E., Hodgson, B. L., Chintawar, S., Crompton, D. E., Hughes, J. N., Bellows, S. T., Klein, K. M., et al. (2013) · Nature Genetics · doi:10.1038/ng.2599 · Cited by 373

Structure of the Human mTOR Complex I and Its Implications for Rapamycin Inhibition

Yip, C. K., Murata, K., Walz, T., Sabatini, D. M., & Kang, S. A. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.05.017 · Cited by 372

NUFIP1 is a ribosome receptor for starvation-induced ribophagy

Wyant, G. A., Abu-Remaileh, M., Frenkel, E. M., Laqtom, N. N., Dharamdasani, V., Lewis, C. A., Chan, S. H., Heinze, I., Ori, A., & Sabatini, D. M. (2018) · Science · doi:10.1126/science.aar2663 · Cited by 363

Recruitment of folliculin to lysosomes supports the amino acid–dependent activation of Rag GTPases

Petit, C. S., Roczniak-Ferguson, A., & Ferguson, S. M. (2013) · Journal of Cell Biology · doi:10.1083/jcb.201307084 · Cited by 355

Activity of rapamycin (AY-22,989) against transplanted tumors.

Eng, C. P., Sehgal, S. N., & Vézina, C. (1984) · The Journal of Antibiotics · doi:10.7164/antibiotics.37.1231 · Cited by 354

SKAR Links Pre-mRNA Splicing to mTOR/S6K1-Mediated Enhanced Translation Efficiency of Spliced mRNAs

Ma, X. M., Yoon, S.-O., Richardson, C. J., Jülich, K., & Blenis, J. (2008) · Cell · doi:10.1016/j.cell.2008.02.031 · Cited by 349

Common corruption of the mTOR signaling network in human tumors

Menon, S., & Manning, B. D. (2008) · Oncogene · doi:10.1038/onc.2009.352 · Cited by 345

KICSTOR recruits GATOR1 to the lysosome and is necessary for nutrients to regulate mTORC1

Wolfson, R. L., Chantranupong, L., Wyant, G. A., Gu, X., Orozco, J. M., Shen, K., Condon, K. J., Petri, S., Kedir, J. F., Scaria, S. M., et al. (2017) · Nature · doi:10.1038/nature21423 · Cited by 345

Architecture of human mTOR complex 1

Aylett, C. H. S., Sauer, E., Imseng, S., Boehringer, D., Hall, M. N., Ban, N., & Maier, T. (2016) · Science · doi:10.1126/science.aaa3870 · Cited by 344

Sestrins inhibit mTORC1 kinase activation through the GATOR complex

Parmigiani, A., Nourbakhsh, A., Ding, B., Wang, W., Kim, Y. C., Akopiants, K., Guan, K.-L., Karin, M., & Budanov, A. V. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.10.019 · Cited by 336

Somatic Mutations Activating the mTOR Pathway in Dorsal Telencephalic Progenitors Cause a Continuum of Cortical Dysplasias

D’Gama, A. M., Woodworth, M. B., Hossain, A. A., Bizzotto, S., Hatem, N. E., LaCoursiere, C. M., Najm, I., Ying, Z., Yang, E., Barkovich, A. J., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.11.106 · Cited by 333

Lewy Body-like α-Synuclein Aggregates Resist Degradation and Impair Macroautophagy

Tanik, S. A., Schultheiss, C. E., Volpicelli-Daley, L. A., Brunden, K. R., & Lee, V. M. Y. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.457408 · Cited by 326

ER–lysosome contacts enable cholesterol sensing by mTORC1 and drive aberrant growth signalling in Niemann–Pick type C

Lim, C.-Y., Davis, O. B., Shin, H. R., Zhang, J., Berdan, C. A., Jiang, X., Counihan, J. L., Ory, D. S., Nomura, D. K., & Zoncu, R. (2019) · Nature Cell Biology · doi:10.1038/s41556-019-0391-5 · Cited by 312

Ribosomal protein S6 kinase activity controls the ribosome biogenesis transcriptional program

Chauvin, C., Koka, V., Nouschi, A., Mieulet, V., Hoareau‐Aveilla, C., Dreazen, A., Cagnard, N., Carpentier, W., Kiss, T., Meyuhas, O., et al. (2013) · Oncogene · doi:10.1038/onc.2012.606 · Cited by 310

Molecular logic of mTORC1 signalling as a metabolic rheostat

Valvezan, A. J., & Manning, B. D. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0038-7 · Cited by 310

Dominant Missense Mutations in a Novel Yeast Protein related to Mammalian Phosphatidylinositol 3-Kinase and VPS34 Abrogate Rapamycin Cytotoxicity

Cafferkey, R., Young, P. R., McLaughlin, M. M., Bergsma, D. J., Koltin, Y., Sathe, G. M., Faucette, L. F., Eng, W.-K., Johnson, R. K., & Livi, G. P. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.10.6012-6023.1993 · Cited by 309

Mechanism of arginine sensing by CASTOR1 upstream of mTORC1

Saxton, R. A., Chantranupong, L., Knockenhauer, K. E., Schwartz, T. U., & Sabatini, D. M. (2016) · Nature · doi:10.1038/nature19079 · Cited by 308

Increased Mammalian Lifespan and a Segmental and Tissue-Specific Slowing of Aging after Genetic Reduction of mTOR Expression

Wu, J. J., Liu, J., Chen, E. B., Wang, J. J., Cao, L., Narayan, N., Fergusson, M. M., Rovira, I. I., Allen, M., Springer, D. A., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.07.030 · Cited by 307

The ketogenic diet inhibits the mammalian target of rapamycin (mTOR) pathway

McDaniel, S. S., Rensing, N. R., Thio, L. L., Yamada, K. A., & Wong, M. L. (2011) · Epilepsia · doi:10.1111/j.1528-1167.2011.02981.x · Cited by 304

mTORC1 Phosphorylates UVRAG to Negatively Regulate Autophagosome and Endosome Maturation

Kim, Y. M., Jung, C. H., Seo, M., Kim, E. K., Park, J.-M., Bae, S. S., & Kim, D. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.11.013 · Cited by 288

Hallmarks of aging: An expanding universe

López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2023) · Cell · doi:10.1016/j.cell.2022.11.001 · Cited by 6,549

Reactive oxygen species (ROS) as pleiotropic physiological signalling agents

Sies, H., & Jones, D. P. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0230-3 · Cited by 5,335

Cancer metabolism: looking forward

Martínez‐Reyes, I., & Chandel, N. S. (2021) · Nature reviews. Cancer · doi:10.1038/s41568-021-00378-6 · Cited by 1,877

Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases

Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193

Targeting cancer metabolism in the era of precision oncology

Stine, Z. E., Schug, Z. T., Salvino, J. M., & Dang, C. V. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00339-6 · Cited by 1,189

mTOR Signaling in Growth Control and Disease

Laplante, M., & Sabatini, D. M. (2012) · Cell · doi:10.1016/j.cell.2012.03.017 · Cited by 8,509

mTOR Signaling in Growth, Metabolism, and Disease

Saxton, R. A., & Sabatini, D. M. (2017) · Cell · doi:10.1016/j.cell.2017.02.004 · Cited by 7,555

mTORC1, the maestro of cell metabolism and growthPreprint

He, L., Cho, S., & Blenis, J. (2024) · Genes & Development · doi:10.1101/gad.352084.124 · Cited by 88

mTOR, Nutrition, and Aging

D’Antona, G. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-801816-3.00011-x · Cited by 3

mTOR: signaling, regulation, effect on metabolism, role in the regulation of life expectancy and tumor growth

Олегович, К. Д., Андреевич, Т. М., & Гребнев, Д. Ю. (2021) · Proceedings of the Komi Science Centre of the Ural Division of the Russian Academy of Sciences · doi:10.19110/1994-5655-2021-5-104-115 · Cited by 4