Dysregulation of the TSC-mTOR pathway in human disease

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

Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease

Ravikumar, B., Vacher, C., Berger, Z., Davies, J. E., Luo, S., Oroz, L. G., Scaravilli, F., Easton, D. F., Duden, R., O'Kane, C. J., et al. (2004) · Nature Genetics · doi:10.1038/ng1362 · Cited by 2,347

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

Two TOR Complexes, Only One of which Is Rapamycin Sensitive, Have Distinct Roles in Cell Growth Control

Loewith, R., Jacinto, E., Wullschleger, S., Lorberg, A., Crespo, J. L., Bonenfant, D., Oppliger, W., Jenoe, P., & Hall, M. N. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00636-6 · Cited by 1,886

The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress

Shaw, R. J., Kosmatka, M., Bardeesy, N., Hurley, R. L., Witters, L. A., DePinho, R. A., & Cantley, L. C. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308061100 · Cited by 1,797

The Tuberous Sclerosis Complex

Crino, P. B., Nathanson, K. L., & Henske, E. P. (2006) · New England Journal of Medicine · doi:10.1056/nejmra055323 · Cited by 1,793

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

LKB1 is the upstream kinase in the AMP-activated protein kinase cascade

Woods, A., Johnstone, S. R., Dickerson, K., Leiper, F. C., Fryer, L. G. D., Neumann, D., Schlattner, U., Wallimann, T., Carlson, M., & Carling, D. (2003) · Current Biology · doi:10.1016/j.cub.2003.10.031 · Cited by 1,650

Mutations of the gene encoding the protein kinase A type I-α regulatory subunit in patients with the Carney complex

Kirschner, L. S., Carney, J. A., Pack, S. D., Taymans, S. E., Giatzakis, C., Cho, Y. S., Cho-Chung, Y. S., & Stratakis, C. A. (2000) · Nature Genetics · doi:10.1038/79238 · Cited by 1,153

mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways

Majumder, P. K., Febbo, P. G., Bikoff, R., Berger, R., Xue, Q., McMahon, L. M., Manola, J., Brugarolas, J., McDonnell, T. J., Golub, T. R., et al. (2004) · Nature Medicine · doi:10.1038/nm1052 · Cited by 964

TOR signaling in growth and metabolism

Wullschleger, S., Loewith, R., & Hall, M. N. (2006) · Cell · doi:10.1016/j.cell.2006.01.016 · Cited by 5,787

Regulation of cancer cell metabolism

Cairns, R. A., Harris, I. S., & Mak, T. W. (2011) · Nature Reviews Cancer · doi:10.1038/nrc2981 · Cited by 4,744

Distinct Roles of Autophagy in the Heart During Ischemia and Reperfusion: Roles of AMP-Activated Protein Kinase and Beclin 1 in Mediating Autophagy

Matsui, Y., Takagi, H., Qu, X., Abdellatif, M., Sakoda, H., Asano, T., Levine, B., & Sadoshima, J. (2007) · Circulation Research · doi:10.1161/01.res.0000261924.76669.36 · Cited by 1,505

Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer

Carracedo, A., Ma, L., Teruya-Feldstein, J., Rojo, F., Salmena, L., Alimonti, A., Egia, A., Sasaki, A. T., Thomas, G., Kozma, S. C., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34739 · Cited by 1,381

Autophagy-Dependent Anticancer Immune Responses Induced by Chemotherapeutic Agents in Mice

Michaud, M., Martins, I., Sukkurwala, A. Q., Adjemian, S., Ma, Y., Pellegatti, P., Shen, S., Kepp, O., Scoazec, M., Mignot, G., et al. (2011) · Science · doi:10.1126/science.1208347 · Cited by 1,377

The plasticity of aging: insights from long-lived mutants

Kenyon, C. (2005) · Cell · doi:10.1016/j.cell.2005.02.002 · Cited by 1,338

Genetic landscape and biomarkers of hepatocellular carcinoma

Zucman-Rossi, J., Villanueva, A., Nault, J.-C., & Llovet, J. M. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.05.061 · Cited by 1,325

Hypothalamic mTOR Signaling Regulates Food Intake

Cota, D., Proulx, K., Smith, K. A. B., Kozma, S. C., Thomas, G., Woods, S. C., & Seeley, R. J. (2006) · Science · doi:10.1126/science.1124147 · Cited by 1,278

The coordinate regulation of the p53 and mTOR pathways in cells

Feng, Z., Zhang, H., Levine, A. J., & Jin, S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0502857102 · Cited by 1,235

Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells

Yilmaz, Ö. H., Valdez, R., Theisen, B. K., Guo, W., Ferguson, D. O., Wu, H., & Morrison, S. J. (2006) · Nature · doi:10.1038/nature04703 · Cited by 1,113

Molecular Interplay between Mammalian Target of Rapamycin (mTOR), Amyloid-β, and Tau

Caccamo, A., Majumder, S., Richardson, A., Strong, R., & Oddo, S. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.100420 · Cited by 881

The mTOR Signalling Pathway in Human Cancer

Pópulo, H., Lopes, J. M., & Soares, P. (2012) · International Journal of Molecular Sciences · doi:10.3390/ijms13021886 · Cited by 830

ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS

Alexander, A., Cai, S.-L., Kim, J., Nanez, A., Sahin, M., MacLean, K. H., Inoki, K., Guan, K.-L., Shen, J., Person, M. D., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0913860107 · Cited by 717

TSC-mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species

Chen, C., Liu, Y., Liu, R., Ikenoue, T., Guan, K.-L., Liu, Y., & Zheng, P. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20081297 · Cited by 682

Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer

King, A., Selak, M. A., & Gottlieb, E. (2006) · Oncogene · doi:10.1038/sj.onc.1209594 · Cited by 672

mTORC1 activation in podocytes is a critical step in the development of diabetic nephropathy in mice

Inoki, K., Mori, H., Wang, J., Suzuki, T., Hong, S., Yoshida, S., Blattner, S. M., Ikenoue, T., Rüegg, M. A., Hall, M. N., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci44771 · Cited by 538

Signalling to translation: How signal transduction pathways control the protein synthetic machinery

Proud, C. G. (2007) · Biochemical Journal · doi:10.1042/bj20070024 · Cited by 520

A Mouse Model of Tuberous Sclerosis: Neuronal Loss of Tsc1 Causes Dysplastic and Ectopic Neurons, Reduced Myelination, Seizure Activity, and Limited Survival

Meikle, L., Talos, D. M., Onda, H., Pollizzi, K., Rotenberg, A., Sahin, M., Jensen, F. E., & Kwiatkowski, D. J. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.5540-06.2007 · Cited by 462

Regulation of mTOR and Cell Growth in Response to Energy Stress by REDD1

Sofer, A., Lei, K., Johannessen, C. M., & Ellisen, L. W. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.14.5834-5845.2005 · Cited by 449

Important role of the LKB1-AMPK pathway in suppressing tumorigenesis in PTEN-deficient mice

Huang, X., Wullschleger, S., Shpiro, N., McGuire, V. A., Sakamoto, K., Woods, Y. L., Mcburnie, W., Fleming, S., & Alessi, D. R. (2008) · Biochemical Journal · doi:10.1042/bj20080557 · Cited by 396

N-Glycans in cancer progression

Lau, K. S., & Dennis, J. W. (2008) · Glycobiology · doi:10.1093/glycob/cwn071 · Cited by 390

Activity of TSC2 is inhibited by AKT-mediated phosphorylation and membrane partitioning

Cai, S.-L., Tee, A. R., Short, J. D., Bergeron, J. M., Kim, J., Shen, J., Guo, R., Johnson, C. L., Kiguchi, K., & Walker, C. L. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200507119 · Cited by 359

Role of mTOR in physiology and pathology of the nervous system

Swiech, L., Perycz, M., Malik, A., & Jaworski, J. (2008) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2007.08.015 · Cited by 338

Tuberous sclerosis: a GAP at the crossroads of multiple signaling pathways

Kwiatkowski, D. J., & Manning, B. D. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi260 · Cited by 332

Mature-onset obesity and insulin resistance in mice deficient in the signaling adapter p62

Rodriguez, A., Durán, A., Selloum, M., Champy, M.-F., Diez-Guerra, F. J., Flores, J. M., Serrano, M., Auwerx, J., Diaz-Meco, M. T., & Moscat, J. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.01.011 · Cited by 290

Activity- and mTOR-dependent suppression of Kv1.1 channel mRNA translation in dendrites

Raab-Graham, K. F., Haddick, P. C. G., Jan, Y. N., & Jan, L. Y. (2006) · Science · doi:10.1126/science.1131693 · Cited by 267

Cell cycle arrest is not yet senescence, which is not just cell cycle arrest: terminology for TOR-driven aging.

Blagosklonny, M. V. (2012) · Aging · doi:10.18632/aging.100443 · Cited by 251

Dissecting the Akt/mammalian target of rapamycin signaling network: emerging results from the head and neck cancer tissue array initiative

Molinolo, A. A., Hewitt, S. M., Amornphimoltham, P., Keelawat, S., Rangdaeng, S., Meneses García, A., Raimondi, A. R., Jufe, R., Itoiz, M., Gao, Y., et al. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-1041 · Cited by 243

Mutations That Increase the Life Span of C. elegans Inhibit Tumor Growth

Pinkston, J. M., Garigan, D., Hansen, M., & Kenyon, C. (2006) · Science · doi:10.1126/science.1121908 · Cited by 242

The Growing Role of mTOR in Neuronal Development and Plasticity

Jaworski, J., & Sheng, M. (2006) · Molecular Neurobiology · doi:10.1385/mn:34:3:205 · Cited by 239

Mammalian target of rapamycin, a molecular target in squamous cell carcinomas of the head and neck

Amornphimoltham, P., Patel, V., Sodhi, A., Nikitakis, N. G., Sauk, J. J., Sausville, E. A., Molinolo, A. A., & Gutkind, J. S. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-0921 · Cited by 238

The Stress-inducted Proteins RTP801 and RTP801L Are Negative Regulators of the Mammalian Target of Rapamycin Pathway

Corradetti, M. N., Inoki, K., & Guan, K.-L. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.c400557200 · Cited by 237

Obesity-Mediated Autophagy Insufficiency Exacerbates Proteinuria-induced Tubulointerstitial Lesions

Yamahara, K., Kume, S., Koya, D., Tanaka, Y., Morita, Y., Chin-Kanasaki, M., Araki, H., Isshiki, K., Araki, S.-I., Haneda, M., et al. (2013) · Journal of the American Society of Nephrology · doi:10.1681/asn.2012111080 · Cited by 213

The LKB1/AMPK signaling pathway has tumor suppressor activity in acute myeloid leukemia through the repression of mTOR-dependent oncogenic mRNA translation

Green, A. S., Chapuis, N., Trovati Maciel, T., Willems, L., Lambert, M., Arnoult, C., Boyer, O., Bardet, V., Park, S., Foretz, M., et al. (2010) · Blood · doi:10.1182/blood-2010-02-269837 · Cited by 199

Stops along the RAS pathway in human genetic disease

Bentires-Alj, M., Kontaridis, M. I., & Neel, B. G. (2006) · Nature Medicine · doi:10.1038/nm0306-283 · Cited by 190

Hypoxia-Inducible Factors (HIFs) and Phosphorylation: Impact on Stability, Localization, and Transactivity

Kietzmann, T., Mennerich, D., & Dimova, E. Y. (2016) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2016.00011 · Cited by 176

Neuronal and glia abnormalities in Tsc1-deficient forebrain and partial rescue by rapamycin

Carson, R. P., Van Nielen, D. L., Winzenburger, P. A., & Ess, K. C. (2012) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.08.024 · Cited by 165

mTOR signaling: implications for cancer and anticancer therapy

Petroulakis, E., Mamane, Y., Le Bacquer, O., Shahbazian, D., & Sonenberg, N. (2006) · British Journal of Cancer · doi:10.1038/sj.bjc.6602902 · Cited by 170

Metformin Targets Multiple Signaling Pathways in Cancer

Lei, Y., Yi, Y., Liu, Y., Liu, X., Keller, E. T., Qian, C.-N., Zhang, J., & Lu, Y. (2017) · Chinese Journal of Cancer · doi:10.1186/s40880-017-0184-9 · Cited by 152

Spatial Memory Formation and Memory-Enhancing Effect of Glucose Involves Activation of the Tuberous Sclerosis Complex–Mammalian Target of Rapamycin Pathway

Dash, P. K., Orsi, S. A., & Moore, A. N. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.0671-06.2006 · Cited by 141

Growth Control Under Stress: mTOR Regulation through the REDD1-TSC Pathway

Ellisen, L. W. (2005) · Cell Cycle · doi:10.4161/cc.4.11.2139 · Cited by 131

Fatty acids are novel nutrient factors to regulate mTORC1 lysosomal localization and apoptosis in podocytes

Yasuda, M., Tanaka, Y., Kume, S., Morita, Y., Chin-Kanasaki, M., Araki, H., Isshiki, K., Araki, S.-I., Koya, D., Haneda, M., et al. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.04.001 · Cited by 123

Reciprocal signaling between translational control pathways and synaptic proteins in autism spectrum disorders

Santini, E., & Klann, E. (2014) · Science Signaling · doi:10.1126/scisignal.2005832 · Cited by 118

The mTOR kinase inhibitor Everolimus decreases S6 kinase phosphorylation but fails to reduce mutant huntingtin levels in brain and is not neuroprotective in the R6/2 mouse model of Huntington's disease

Fox, J. H., Connor, T., Chopra, V., Dorsey, K., Kama, J. A., Bleckmann, D., Betschart, C., Hoyer, D., Frentzel, S., DiFiglia, M., et al. (2010) · Molecular Neurodegeneration · doi:10.1186/1750-1326-5-26 · Cited by 94

Crystal structure of the Gtr1p–Gtr2p complex reveals new insights into the amino acid-induced TORC1 activation

Gong, R., Li, L., Liu, Y., Wang, P., Yang, H., Wang, L., Cheng, J., Guan, K.-L., & Xu, Y. (2011) · Genes & Development · doi:10.1101/gad.16968011 · Cited by 98

4.4 Å Resolution Cryo-EM structure of human mTOR Complex 1

Yang, H., Wang, J., Liu, M., Chen, X., Huang, M., Tan, D., Dong, M.-Q., Wong, C. C. L., Wang, J., Xu, Y., et al. (2016) · Protein & Cell · doi:10.1007/s13238-016-0346-6 · Cited by 96

Met acts on Mdm2 via mTOR to signal cell survival during development

Moumen, A., Patané, S., Porras, A., Dono, R., & Maina, F. (2007) · Development · doi:10.1242/dev.02820 · Cited by 95

The pleiotropic roles of autophagy regulators in melanogenesis

Ho, H., & Ganesan, A. K. (2011) · Pigment Cell & Melanoma Research · doi:10.1111/j.1755-148x.2011.00889.x · Cited by 88

Long-term metformin use may improve clinical outcomes in diabetic patients with non-alcoholic steatohepatitis and bridging fibrosis or compensated cirrhosis

Vilar‐Gomez, E., Vuppalanchi, R., Desai, A. P., Gawrieh, S., Ghabril, M., Saxena, R., Cummings, O. W., & Chalasani, N. (2019) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.15331 · Cited by 84

The tuberous sclerosis complex proteins – a GRIPP on cognition and neurodevelopment

de Vries, P. J., & Howe, C. J. (2007) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2007.06.003 · Cited by 84

Defects in GABA metabolism affect selective autophagy pathways and are alleviated by mTOR inhibition

Lakhani, R., Vogel, K. R., Till, A., Liu, J., Burnett, S. F., Gibson, K. M., & Subramani, S. (2014) · EMBO Molecular Medicine · doi:10.1002/emmm.201303356 · Cited by 75

Signaling Pathway Mediating Myeloma Cell Growth and Survival

Hideshima, T., & Anderson, K. C. (2021) · Cancers · doi:10.3390/cancers13020216 · Cited by 70

Targeting mTOR signaling overcomes acquired resistance to combined BRAF and MEK inhibition in BRAF-mutant melanoma

Wang, B., Zhang, W., Zhang, G., Kwong, L., Lu, H., Tan, J., Sadek, N., Xiao, M., Zhang, J., Labrie, M., et al. (2021) · Oncogene · doi:10.1038/s41388-021-01911-5 · Cited by 66

Structural Basis of the Interaction between Tuberous Sclerosis Complex 1 (TSC1) and Tre2-Bub2-Cdc16 Domain Family Member 7 (TBC1D7)

Qin, J., Wang, Z., Hoogeveen-Westerveld, M., Shen, G., Gong, W., Nellist, M., & Xu, W. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.701870 · Cited by 37

Astragalus Polysaccharide Improves Muscle Atrophy from Dexamethasone- and Peroxide-Induced Injury in Vitro

Lu, L., Wang, D.-T., Shi, Y., Yin, Y., Wei, L.-B., Zou, Y.-C., Huang, B., Zhao, Y., Wang, M., Wan, H., et al. (2013) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2013.06.027 · Cited by 33

Crystal structure of the yeast TSC1 core domain and implications for tuberous sclerosis pathological mutations

Sun, W., Zhu, Y. J., Wang, Z., Zhong, Q., Gao, F., Lou, J., Gong, W., & Xu, W. (2013) · Nature Communications · doi:10.1038/ncomms3135 · Cited by 27