Cited by 828PI3K/AKT/mTOR signaling in cancerTuberous Sclerosis Complex ResearchMetabolism, Diabetes, and Cancer

The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.

Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling

Open access

Tee, Andrew R., Fingar, Diane C., Manning, Brendan D., Kwiatkowski, David J., Cantley, Lewis C., Blenis, John·2002·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.202476899PMC PMC129715

Open this paper in CoChat — free account

Abstract

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder that occurs upon mutation of either the TSC1 or TSC2 genes, which encode the protein products hamartin and tuberin, respectively. Here, we show that hamartin and tuberin function together to inhibit mammalian target of rapamycin (mTOR)-mediated signaling to eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase 1 (S6K1). First, coexpression of hamartin and tuberin repressed phosphorylation of 4E-BP1, resulting in increased association of 4E-BP1 with eIF4E; importantly, a mutant of TSC2 derived from TSC patients was defective in repressing phosphorylation of 4E-BP1. Second, the activity of S6K1 was repressed by coexpression of hamartin and tuberin, but the activity of rapamycin-resistant mutants of S6K1 were not affected, implicating mTOR in the TSC-mediated inhibitory effect on S6K1. Third, hamartin and tuberin blocked the ability of amino acids to activate S6K1 within nutrient-deprived cells, a process that is dependent on mTOR. These findings strongly implicate the tuberin-hamartin tumor suppressor complex as an inhibitor of mTOR and suggest that the formation of tumors within TSC patients may result from aberrantly high levels of mTOR-mediated signaling to downstream targets.

Integrity signals

Registry

Crossref · 10.1073/pnas.202476899

Cites

31 of 31 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

TOR, a Central Controller of Cell Growth
Schmelzle, T., & Hall, M. N. (2000) · Cell · doi:10.1016/s0092-8674(00)00117-3 · Cited by 1,914
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
Self-citation
Regulation of translation initiation by FRAP/mTOR
Gingras, A.-C., Raught, B., & Sonenberg, N. (2001) · Genes & Development · doi:10.1101/gad.887201 · Cited by 1,545
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
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
Self-citation
Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E
Fingar, D. C., Salama, S., Tsou, C., Harlow, E., & Blenis, J. (2002) · Genes & Development · doi:10.1101/gad.995802 · Cited by 1,093
Self-citation
Malignant transformation by a eukaryotic initiation factor subunit that binds to mRNA 5' cap
Lazaris-Karatzas, A., Montine, K. S., & Sonenberg, N. (1990) · Nature · doi:10.1038/345544a0 · Cited by 971
Mammalian TOR: a homeostatic ATP sensor
Dennis, P. B., Jaeschke, A., Saitoh, M., Fowler, B., Kozma, S. C., & Thomas, G. (2001) · Science · doi:10.1126/science.1063518 · Cited by 962
A mouse model of TSC1 reveals sex-dependent lethality from liver hemangiomas, and up-regulation of p70S6 kinase activity in Tsc1 null cells
Kwiatkowski, D. J. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.5.525 · Cited by 674
Self-citation
The mRNA 5′ cap-binding protein eIF4E and control of cell growth
Sonenberg, N., & Gingras, A. (1998) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(98)80150-6 · Cited by 673

Flagged first, then by citations

Show all 31 references

Research works printed but not linked: 4

E R Gomez, J R Sampson, V H Whittemore Developmental Perspectives in Psychiatry (Oxford Univ. Press, Oxford, 1999).
T L Plank, R S Yeung, E P Henske Cancer Res 58, 4766–4770 (1998).
Martin K. A. & Blenis J. (2002) Adv. Cancer Res. 86 in press.
D Rousseau, A C Gingras, A Pause, N Sonenberg Oncogene 13, 2415–2420 (1996).

Sorted by citations

Items 301–400 of 828

Decanoic acid inhibits mTORC1 activity independent of glucose and insulin signaling
Warren, E. C., Dooves, S., Lugarà, E., Damstra‐Oddy, J., Schaf, J., Heine, V. M., Walker, M. C., & Williams, R. S. B. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2008980117 · Cited by 66
Structure–Function Relationships Underlying the Capacity of Bordetella Adenylate Cyclase Toxin to Disarm Host Phagocytes
Novák, J., Černý, O., Osic̆ková, A., Linhartová, I., Mašín, J., Bumba, L., Šebo, P., & Osička, R. (2017) · Toxins · doi:10.3390/toxins9100300 · Cited by 62
mTOR inhibitor therapy as a disease modifying therapy for tuberous sclerosis complex
Franz, D. N., & Krueger, D. A. (2018) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.31655 · Cited by 62
First left-right comparative study of topical rapamycin vs. vehicle for facial angiofibromas in patients with tuberous sclerosis complex
Tanaka, M., Wataya‐Kaneda, M., Nakamura, A., Matsumoto, S., & Katayama, I. (2013) · British Journal of Dermatology · doi:10.1111/bjd.12567 · Cited by 61
Akt regulates nuclear/cytoplasmic localization of tuberin
Rosner, M., Freilinger, A., & Hengstschläger, M. (2006) · Oncogene · doi:10.1038/sj.onc.1209812 · Cited by 61
The impact of cow's milk-mediated mTORC1-signaling in the initiation and progression of prostate cancer
Melnik, B. C., John, S. M., Carrera‐Bastos, P., & Cordain, L. (2012) · Nutrition & Metabolism · doi:10.1186/1743-7075-9-74 · Cited by 63
Editorial (Hot Topic: Inhibition of PI3K/Akt/mTOR Signaling by Natural Products)
Huang, S. (2013) · Anti-Cancer Agents in Medicinal Chemistry · doi:10.2174/1871520611313070001 · Cited by 62
Targeting the PI3K Pathway for Cancer Therapy
Sadeghi, N., & Gerber, D. E. (2012) · Future Medicinal Chemistry · doi:10.4155/fmc.12.56 · Cited by 59
Management of side effects of mTOR inhibitors in tuberous sclerosis patients
Sadowski, K., Kotulska, K., & Jóźwiak, S. (2016) · Pharmacological Reports · doi:10.1016/j.pharep.2016.01.005 · Cited by 60
Hamartin regulates cessation of mouse nephrogenesis independently of Mtor
Volovelsky, O., Nguyen, T., Jarmas, A. E., Combes, A. N., Wilson, S. B., Little, M. H., Witte, D. P., Brunskill, E. W., & Kopan, R. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1712955115 · Cited by 58
Interaction of FoxO1 and TSC2 Induces Insulin Resistance through Activation of the Mammalian Target of Rapamycin/p70 S6K Pathway
Cao, Y., Kamioka, Y., Yokoi, N., Kobayashi, T., Hino, O., Onodera, M., Mochizuki, N., & Nakae, J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m608116200 · Cited by 60
Anti-Myeloma Activity of Akt Inhibition Is Linked to the Activation Status of PI3K/Akt and MEK/ERK Pathway
Ramakrishnan, V. G., Kimlinger, T. K., Haug, J. L., Painuly, U., Wellik, L. E., Halling, T. M., Rajkumar, S. V., & Kumar, S. K. (2012) · PLoS ONE · doi:10.1371/journal.pone.0050005 · Cited by 60
Effects of rapamycin on gene expression, morphology, and electrophysiological properties of rat hippocampal neurons
Rüegg, S. J., Baybis, M., Juul, H., Dichter, M. A., & Crino, P. B. (2007) · Epilepsy Research · doi:10.1016/j.eplepsyres.2007.09.009 · Cited by 59
Applying the Lessons of Tuberous Sclerosis: The 2015 Hower Award Lecture
Roach, E. S. (2016) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2016.07.003 · Cited by 60
Efficacy and safety of Everolimus in children with TSC - associated epilepsy – Pilot data from an open single-center prospective study
Samueli, S., Abraham, K., Dressler, A., Gröppel, G., Mühlebner, A., Scholl, T., Kasprian, G. J., Laccone, F. A., & Feucht, M. (2016) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-016-0530-z · Cited by 59
Lymphangioleiomyomatosis (LAM): Molecular insights lead to targeted therapies
Glasgow, C. G., Steagall, W. K., Taveira‐DaSilva, A. M., Pacheco–Rodriguez, G., Cai, X., El‐Chemaly, S., Moses, M. A., Darling, T. N., & Moss, J. (2010) · Respiratory Medicine · doi:10.1016/j.rmed.2010.03.017 · Cited by 57
Inhibition of mTOR Pathway by Rapamycin Reduces Brain Damage in Rats Subjected to Transient Forebrain Ischemia
Yang, X. C., Hei, C., Liu, P., Song, Y., Thomas, T., Tshimanga, S., Wang, F., Niu, J., Sun, T., & Li, P. A. (2015) · International Journal of Biological Sciences · doi:10.7150/ijbs.12930 · Cited by 57
PHYSIOLOGY AND ENDOCRINOLOGY SYMPOSIUM: Roles for insulin-supported skeletal muscle growth1,2
Rhoads, R. P., Baumgard, L. H., El‐Kadi, S. W., & Zhao, L. D. (2016) · Journal of Animal Science · doi:10.2527/jas.2015-0110 · Cited by 56
TSC1 loss increases risk for tauopathy by inducing tau acetylation and preventing tau clearance via chaperone-mediated autophagy
Alquezar, C., Schoch, K. M., Geier, E. G., Ramos, E. M., Scrivo, A., Li, K. H., Argouarch, A. R., Mlynarski, E. E., Dombroski, B., DeTure, M., et al. (2021) · Science Advances · doi:10.1126/sciadv.abg3897 · Cited by 56
Altered mTOR Signaling in Senescent Retinal Pigment Epithelium
Chen, Y., Wang, J., Cai, J., & Sternberg, P. (2010) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.10-5280 · Cited by 57
Sleep, Plasticity and the Pathophysiology of Neurodevelopmental Disorders: The Potential Roles of Protein Synthesis and Other Cellular Processes
Picchioni, D., Reith, R. M., Nadel, J., & Smith, C. B. (2014) · Brain Sciences · doi:10.3390/brainsci4010150 · Cited by 56
Excessive Leucine-mTORC1-Signalling of Cow Milk-Based Infant Formula: The Missing Link to Understand Early Childhood Obesity
Melnik, B. C. (2012) · Journal of Obesity · doi:10.1155/2012/197653 · Cited by 57
m‐ TOR inhibitors and their potential role in haematological malignancies
Calimeri, T., & Ferreri, A. J. M. (2017) · British Journal of Haematology · doi:10.1111/bjh.14529 · Cited by 57
Loss of a Negative Regulator of mTORC1 Induces Aerobic Glycolysis and Altered Fiber Composition in Skeletal Muscle
Dutchak, P. A., Estill-Terpack, S. J., Plec, A. A., Zhao, X., Yang, C., Chen, J., Ko, B., Deberardinis, R. J., Yu, Y., & Tu, B. P. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.04.058 · Cited by 53
Epilepsy surgery and tuberous sclerosis complex: special considerations
Bollo, R. J., Kalhorn, S. P., Carlson, C., Haegeli, V., Devinsky, O., & Weiner, H. L. (2008) · Neurosurgical FOCUS · doi:10.3171/foc/2008/25/9/e13 · Cited by 56
The Mammalian Target of Rapamycin Pathway as a Potential Target for Cancer Chemoprevention
Kopelovich, L., Fay, J. R., Sigman, C. C., & Crowell, J. A. (2007) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-07-0045 · Cited by 54
The role of cell signaling in poxvirus tropism: The case of the M-T5 host range protein of myxoma virus
Werden, S. J., & McFadden, G. (2007) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2007.08.001 · Cited by 57
Functional interaction of mammalian target of rapamycin complexes in regulating mammalian cell size and cell cycle
Rosner, M., Fuchs, C., Siegel, N., Valli, A., & Hengstschläger, M. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp271 · Cited by 55
Is Epilepsy a Preventable Disorder? New Evidence from Animal Models
Giblin, K. A., & Blumenfeld, H. (2010) · The Neuroscientist · doi:10.1177/1073858409354385 · Cited by 56
Emerging Pharmacotherapies for Neurodevelopmental Disorders
Wetmore, D. Z., & Garner, C. C. (2010) · Journal of Developmental & Behavioral Pediatrics · doi:10.1097/dbp.0b013e3181ee3833 · Cited by 56
Tsc1 represses parvalbumin expression and fast-spiking properties in somatostatin lineage cortical interneurons
Malik, R., Pai, E. L.-L., Rubin, A. N., Stafford, A. M., Angara, K., Minasi, P., Rubenstein, J. L. R., Sohal, V. S., & Vogt, D. L. (2019) · Nature Communications · doi:10.1038/s41467-019-12962-4 · Cited by 55
Analyzing the Potential Biological Determinants of Autism Spectrum Disorder: From Neuroinflammation to the Kynurenine Pathway
Savino, R., Carotenuto, M., Polito, A. N., Noia, S. D., Albenzio, M., Scarinci, A., Ambrosi, A., Sessa, F., Tartaglia, N., & Messina, G. (2020) · Brain Sciences · doi:10.3390/brainsci10090631 · Cited by 53
Perturbed IFN-γ-Jak-Signal Transducers and Activators of Transcription Signaling in Tuberous Sclerosis Mouse Models
El-Hashemite, N., Zhang, H., Walker, V., Hoffmeister, K. M., & Kwiatkowski, D. J. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-3609 · Cited by 54
Self-citation
Genetic Variants in the PI3K/PTEN/AKT/mTOR Pathway Predict Head and Neck Cancer Patient Second Primary Tumor/Recurrence Risk and Response to Retinoid Chemoprevention
Hildebrandt, M. A. T., Lippman, S. M., Etzel, C. J., Kim, E., Lee, J. J., Khuri, F. R., Spitz, M. R., Lotan, R., Hong, W. K., & Wu, X. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-3271 · Cited by 53
Next Generation Strategies for Geroprotection via mTORC1 Inhibition
Dumas, S. N., & Lamming, D. W. (2019) · The Journals of Gerontology Series A · doi:10.1093/gerona/glz056 · Cited by 53
The Ion Transporter NKCC1 Links Cell Volume to Cell Mass Regulation by Suppressing mTORC1
Demian, W. L., Persaud, A. K., Jiang, C., Coyaud, É., Liu, S., Kapùs, A., Kafri, R., Raught, B., & Rotin, D. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.04.034 · Cited by 54
The PTEN/Akt Pathway Dictates the Direct αVβ3-Dependent Growth-Inhibitory Action of an Active Fragment of Tumstatin in Glioma Cells In vitro and In vivo
Kawaguchi, T., Yamashita, Y., Kanamori, M., Endersby, R., Bankiewicz, K. S., Baker, S. J., Bergers, G., & Pieper, R. O. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-1540 · Cited by 53
Meal feeding enhances formation of eIF4F in skeletal muscle: role of increased eIF4E availability and eIF4G phosphorylation
Vary, T. C., & Lynch, C. J. (2005) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00460.2005 · Cited by 55
The UK guidelines for management and surveillance of Tuberous Sclerosis Complex
Amin, S., Kingswood, J. C., Bolton, P., Elmslie, F., Gale, D. P., Harland, C. C., Johnson, S. R., Parker, A. P. J., Sampson, J. R., Smeaton, M., et al. (2018) · QJM · doi:10.1093/qjmed/hcy215 · Cited by 52
TSC1 involvement in bladder cancer: diverse effects and therapeutic implications
Guo, Y., Chekaluk, Y. I., Zhang, J., Du, J., Gray, N. S., Wu, C., & Kwiatkowski, D. J. (2013) · The Journal of Pathology · doi:10.1002/path.4176 · Cited by 54
Self-citation
Orexin/Hypocretin Activates mTOR Complex 1 (mTORC1) via an Erk/Akt-independent and Calcium-stimulated Lysosome v-ATPase Pathway
Wang, Z., Liu, S., Kakizaki, M., Hirose, Y., Ishikawa, Y., Funato, H., Yanagisawa, M., Yu, Y., & Liu, Q. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.600015 · Cited by 52
Emerging Role of mTOR Signaling‐Related miRNAs in Cardiovascular Diseases
Samidurai, A., Kukreja, R. C., & Das, A. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/6141902 · Cited by 51
Mammalian target of rapamycin and tuberous sclerosis complex
Wataya‐Kaneda, M. (2015) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2015.04.005 · Cited by 54
IL-10 Function, Regulation, and in Bacterial Keratitis
Hazlett, L. D., Jiang, X., & McClellan, S. A. (2014) · Journal of Ocular Pharmacology and Therapeutics · doi:10.1089/jop.2014.0018 · Cited by 54
Human Chorionic Gonadotropin Stimulates Theca-Interstitial Cell Proliferation and Cell Cycle Regulatory Proteins by a cAMP-Dependent Activation of AKT/mTORC1 Signaling Pathway
Palaniappan, M., & Menon, K. (2010) · Molecular Endocrinology · doi:10.1210/me.2010-0044 · Cited by 51
CRKL regulates alternative splicing of cancer-related genes in cervical cancer samples and HeLa cell
Song, Q., Yi, F., Zhang, Y., Li, D. K. J., Wei, Y., Yu, H., & Zhang, Y. (2019) · BMC Cancer · doi:10.1186/s12885-019-5671-8 · Cited by 50
Advances in the treatment of tuberous sclerosis complex
Leclezio, L., & de Vries, P. J. (2015) · Current Opinion in Psychiatry · doi:10.1097/yco.0000000000000136 · Cited by 51
Thoracic aortic disease in tuberous sclerosis complex: molecular pathogenesis and potential therapies in Tsc2+/− mice
Cao, J., Gong, L., Guo, D., Mietzsch, U., Kuang, S.-Q., Kwartler, C. S., Safi, H. J., Estrera, A. L., Gambello, M. J., & Milewicz, D. M. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq066 · Cited by 50
Requirement for lysosomal localization of mTOR for its activation differs between leucine and other amino acids
Avérous, J., Lambert-Langlais, S., Carraro, V., Gourbeyre, O., Parry, L., B'Chir, W., Muranishi, Y., Jousse, C., Bruhat, A., Maurin, A., et al. (2014) · Cellular Signalling · doi:10.1016/j.cellsig.2014.04.019 · Cited by 53
The Serine Protease HtrA1 Specifically Interacts and Degrades the Tuberous Sclerosis Complex 2 Protein
Campioni, M., Severino, A., Manente, L., Tuduce, I. L., Toldo, S. A., Caraglia, M., Crispi, S., Ehrmann, M., He, X., Maguire, J. L., et al. (2010) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-09-0473 · Cited by 50
Troglitazone acutely inhibits protein synthesis in endothelial cells via a novel mechanism involving protein phosphatase 2A-dependent p70 S6 kinase inhibition
Cho, D., Choi, Y. J., Jo, S. A., Ryou, J., Kim, J. Y., Chung, J., & Jo, I. (2006) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00491.2005 · Cited by 49
DEPDC5 as a potential therapeutic target for epilepsy
Myers, K. A., & Scheffer, I. E. (2017) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2017.1316715 · Cited by 50
mTOR Inhibition and its Effect on Cancer in Transplantation
Andrassy, J., Graeb, C., Rentsch, M., Jauch, K.-W., & Guba, M. O. (2005) · Transplantation · doi:10.1097/01.tp.0000186912.23630.85 · Cited by 49
Phosphoinositide 3-Kinase Activation Regulates Cell Division Time by Coordinated Control of Cell Mass and Cell Cycle Progression Rate
Álvarez, B., Garrido, E., García‐Sanz, J. A., & Carrera, A. C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300663200 · Cited by 49
Chemical Inhibitors and microRNAs (miRNA) Targeting the Mammalian Target of Rapamycin (mTOR) Pathway: Potential for Novel Anticancer Therapeutics
Alqurashi, N., Hashimi, S. M., & Wei, M. Q. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms14023874 · Cited by 47
Identification of FUSE-binding protein 1 as a regulatory mRNA-binding protein that represses nucleophosmin translation
Olanich, M. E., Moss, B. L., Piwnica-Worms, D., Townsend, R. R., & Weber, J. D. (2010) · Oncogene · doi:10.1038/onc.2010.404 · Cited by 49
Value of fetal cerebral MRI in sonographically proven cardiac rhabdomyoma
Mühler, M. R., Rake, A., Schwabe, M., Schmidt, S. A. C., Kivelitz, D. E., Chaoui, R., & Hamm, B. (2007) · Pediatric Radiology · doi:10.1007/s00247-007-0436-y · Cited by 48
Characterisation of a novel TSC2 missense mutation in the GAP related domain associated with minimal clinical manifestations of tuberous sclerosis
Mayer, K., Goedbloed, M., van Zijl, K., Nellist, M. D., & Rott, H. ‐. (2004) · Journal of Medical Genetics · doi:10.1136/jmg.2003.010835 · Cited by 48
Discovery of the PTEN Tumor Suppressor and Its Connection to the PI3K and AKT OncogenesPreprint
Parsons, R. E. (2020) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a036129 · Cited by 48
p27 Kip1 localization depends on the tumor suppressor protein tuberin
Rosner, M., Freilinger, A., Hanneder, M., Fujita, N., Lübec, G., Tsuruo, T., & Hengstschläger, M. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm103 · Cited by 46
Positive and Negative Regulation of TSC2 Activity and Its Effects on Downstream Effectors of the mTOR Pathway
Jozwiak, J., Jozwiak, S., Grzela, T., & Lazarczyk, M. (2005) · NeuroMolecular Medicine · doi:10.1385/nmm:7:4:287 · Cited by 63
Discovery of Rare Mutations in Autism: Elucidating Neurodevelopmental Mechanisms
Uzun, E. D. G., Sciarra, L. N., Maguire, A. M., Pescosolido, M. F., van Dyck, L. I., & Morrow, E. M. (2015) · Neurotherapeutics · doi:10.1007/s13311-015-0363-9 · Cited by 45
TOR and MAP kinase pathways synergistically regulate autophagy in response to nutrient depletion in fission yeast
Corral-Ramos, C., Barrios, R., Ayté, J., & Hidalgo, E. (2021) · Autophagy · doi:10.1080/15548627.2021.1935522 · Cited by 47
Regulation of Hematopoiesis and Methionine Homeostasis by mTORC1 Inhibitor NPRL2
Dutchak, P. A., Laxman, S., Estill, S. J., Wang, C., Wang, Y., Wang, Y., Bulut, G. B., Gao, J., Huang, L. J.-S., & Tu, B. P. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.06.042 · Cited by 48
PTEN/PI3K and MAPK signaling in protection and pathology following CNS injuries
Walker, C. L., Liu, N., & Xu, X. (2013) · Frontiers in Biology · doi:10.1007/s11515-013-1255-1 · Cited by 48
Pharmacological and Genetic Evaluation of Proposed Roles of Mitogen-activated Protein Kinase/Extracellular Signal-regulated Kinase Kinase (MEK), Extracellular Signal-regulated Kinase (ERK), and p90RSK in the Control of mTORC1 Protein Signaling by Phorbol Esters
Fonseca, B. D., Alain, T., Finestone, L. K., Huang, B., Rolfe, M. J., Jiang, T., Yao, Z., Hernández, G., Bennett, C. F., & Proud, C. G. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.260794 · Cited by 45
Innovations therapy: mammalian target of rapamycin (mTOR) inhibitors for the treatment of neuroendocrine tumors
Capdevila, J., Salazar, R., Halperín, I., Abad, A., & Yao, J. C. (2011) · Cancer and Metastasis Reviews · doi:10.1007/s10555-011-9290-3 · Cited by 44
Preclinical validation of AR42, a novel histone deacetylase inhibitor, as treatment for vestibular schwannomas
Jacob, A., Oblinger, J. L., Bush, M. L., Brendel, V. J., Santarelli, G. D., Chaudhury, A. R., Kulp, S. K., Perle, K. M. D. L., Chen, C., Chang, L., et al. (2011) · The Laryngoscope · doi:10.1002/lary.22392 · Cited by 43
Tuberin activates the proapoptotic molecule BAD
Freilinger, A., Rosner, M., Krupitza, G., Nishino, M., Lübec, G., Korsmeyer, S. J., & Hengstschläger, M. (2006) · Oncogene · doi:10.1038/sj.onc.1209660 · Cited by 44
PIP4kγ is a substrate for mTORC1 that maintains basal mTORC1 signaling during starvation
Mackey, A. M., Sarkes, D. A., Bettencourt, I. A., Asara, J. M., & Rameh, L. E. (2014) · Science Signaling · doi:10.1126/scisignal.2005191 · Cited by 44
Protein profile of the HeLa cell line
Fountoulakis, M., Tsangaris, G. T., Oh, J., Maris, A., & Lübec, G. (2004) · Journal of Chromatography A · doi:10.1016/j.chroma.2004.03.032 · Cited by 43
The Mammalian Target of Rapamycin-p70 Ribosomal S6 Kinase but Not Phosphatidylinositol 3-Kinase-Akt Signaling Is Responsible for Fibroblast Growth Factor-9-induced Cell Proliferation
Wing, L.-Y. C., Chen, H.-M., Chuang, P., Wu, M.-H., & Tsai, S. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m411865200 · Cited by 44
The mTOR Pathway in Breast Cancer
Hynes, N. E., & Boulay, A. (2006) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1007/s10911-006-9012-6 · Cited by 46
Mammalian Target of Rapamycin Complex 1 (mTORC1) Enhances Bortezomib-induced Death in Tuberous Sclerosis Complex (TSC)-null Cells by a c-MYC-dependent Induction of the Unfolded Protein Response
Babcock, J. T., Nguyen, H., He, Y., Hendricks, J. W., Wek, R. C., & Quilliam, L. A. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.431056 · Cited by 43
FK506 can activate transforming growth factor- signalling in vascular smooth muscle cells and promote proliferation
Giordano, A., Romano, S., Mallardo, M., D'Angelillo, A., Calı̀, G., Corcione, N., Ferraro, P., & Romano, M. F. (2008) · Cardiovascular Research · doi:10.1093/cvr/cvn079 · Cited by 43
Thyroid-stimulating Hormone/cAMP and Glycogen Synthase Kinase 3β Elicit Opposing Effects on Rap1GAP Stability
Tsygankova, O. M., Feshchenko, E. A., Klein, P. S., & Meinkoth, J. L. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m305824200 · Cited by 42
Treatment of Pediatric Low-Grade Gliomas
Sait, S. F., Giantini-Larsen, A., Tringale, K. R., Souweidane, M. M., & Karajannis, M. A. (2023) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-023-01257-3 · Cited by 45
Oncogenes strike a balance between cellular growth and homeostasis
Qiu, B., & Simon, M. C. (2015) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2015.08.005 · Cited by 44
The outcome of surgical management of subependymal giant cell astrocytoma in tuberous sclerosis complex
Amin, S., Carter, M., Edwards, R. J., Pople, I. K., Aquilina, K., Merrifield, J., Osborne, J. P., & O'Callaghan, F. J. (2012) · European Journal of Paediatric Neurology · doi:10.1016/j.ejpn.2012.10.005 · Cited by 41
Assessing the outcomes of everolimus on renal angiomyolipoma associated with tuberous sclerosis complex in China: a two years trial
Cai, Y., Guo, H., Wang, W., Li, H., Sun, H., Shi, B., & Zhang, Y. (2018) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-018-0781-y · Cited by 41
Tuberous sclerosis‐associated neuropsychiatric disorders: a paediatric cohort study
Toldo, I., Brasson, V., Miscioscia, M., Pelizza, M. F., Manara, R., Sartori, S., Mantegazza, G., Vecchi, M., Nosadini, M., & Gatta, M. (2018) · Developmental Medicine & Child Neurology · doi:10.1111/dmcn.14055 · Cited by 41
RIPK1 Promotes Energy Sensing by the mTORC1 Pathway
Najafov, A., Luu, H. S., Mookhtiar, A. K., Mifflin, L., Xia, H., Amin, P. P., Ordureau, A., Wang, H., & Yuan, J. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.11.008 · Cited by 40
Sphingosine 1-phosphate metabolism and insulin signaling
Wigger, D., Schumacher, F., Schneider‐Schaulies, S., & Kleuser, B. (2021) · Cellular Signalling · doi:10.1016/j.cellsig.2021.109959 · Cited by 44
A Novel Covalent mTOR Inhibitor, DHM25, Shows in Vivo Antitumor Activity against Triple-Negative Breast Cancer Cells
Fouqué, A., Delalande, O., Jean, M., Castellano, R., Josselin, E., Malleter, M., Shoji, K. F., Mac, D. H., Rampanarivo, H., Collette, Y., et al. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b00991 · Cited by 40
Quality of life in patients with Tuberous Sclerosis Complex (TSC)
Amin, S., Mallick, A. A., Lux, A. L., & O'Callaghan, F. J. (2019) · European Journal of Paediatric Neurology · doi:10.1016/j.ejpn.2019.09.006 · Cited by 41
Iron chelation inhibits mTORC1 signaling involving activation of AMPK and REDD1/Bnip3 pathways
Shang, C., Zhou, H., Liu, W., Shen, T., Luo, Y., & Huang, S. (2020) · Oncogene · doi:10.1038/s41388-020-1366-5 · Cited by 43
Current Sarcoidosis Models and the Importance of Focusing on the Granuloma
Locke, L. W., Schlesinger, L. S., & Crouser, E. D. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01719 · Cited by 40
mTORC1 links pathology in experimental models of Still’s disease and macrophage activation syndrome
Huang, Z., You, X., Chen, L., Du, Y., Brodeur, K. E., Jee, H., Wang, Q., Linder, G., Darbousset, R., Cunin, P., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-34480-6 · Cited by 39
Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer
Xi, Y., Nakajima, G., Schmitz, J. C., Chu, E., & Ju, J. (2006) · BMC Genomics · doi:10.1186/1471-2164-7-68 · Cited by 39
Analysis of the regulatory motifs in eukaryotic initiation factor 4E‐binding protein 1
Lee, V. H.-Y., Healy, T. M., Fonseca, B. D., Hayashi, A. A., & Proud, C. G. (2008) · FEBS Journal · doi:10.1111/j.1742-4658.2008.06372.x · Cited by 41
Specific interaction between S6K1 and CoA synthase: a potential link between the mTOR/S6K pathway, CoA biosynthesis and energy metabolism
Nemazanyy, I., Panasyuk, G., Zhyvoloup, A., Panayotou, G., Gout, I. T., & Filonenko, V. V. (2004) · FEBS Letters · doi:10.1016/j.febslet.2004.10.091 · Cited by 41
Mammalian Target of Rapamycin Regulates the Growth of Mammary Epithelial Cells through the Inhibitor of Deoxyribonucleic Acid Binding Id1 and Their Functional Differentiation through Id2
Jankiewicz, M., Groner, B., & Desrivières, S. (2006) · Molecular Endocrinology · doi:10.1210/me.2006-0071 · Cited by 41
Expression profiling in tuberous sclerosis complex (TSC) knockout mouse astrocytes to characterize human TSC brain pathology
Ess, K. C., Uhlmann, E. J., Li, W., Li, H., DeClue, J. E., Crino, P. B., & Gutmann, D. H. (2004) · Glia · doi:10.1002/glia.10324 · Cited by 40
The tuberous sclerosis genes and regulation of the cyclin-dependent kinase inhibitor p27
ROSNER, M., Freilinger, A., & HENGSTSCHLAGER, M. (2006) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2006.03.001 · Cited by 39
Isolation and Growth of Smooth Muscle-Like Cells Derived from Tuberous Sclerosis Complex-2 Human Renal Angiomyolipoma
Lesma, E. A., Grande, V., Carelli, S., Brancaccio, D., Canevini, M. P., Alfano, R. M., Coggi, G., Giulio, A. M. D., & Gorio, A. (2005) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)61198-4 · Cited by 40
Efficacy and Safety of Sirolimus for Renal Angiomyolipoma in Patients with Tuberous Sclerosis Complex or Sporadic Lymphangioleiomyomatosis: A Systematic Review
Peng, Z., Yang, L., Wang, T., Han, P., Liu, Z., & Wei, Q. (2014) · The Journal of Urology · doi:10.1016/j.juro.2014.04.096 · Cited by 39
Metformin: An Inhibitor of mTORC1 Signaling
Melnik, B. C., & Schmitz, G. (2014) · Cited by 39
Metabolic Control of Plasma Cell Differentiation- What We Know and What We Don't Know
Aronov, M., & Tirosh, B. (2016) · Journal of Clinical Immunology · doi:10.1007/s10875-016-0246-9 · Cited by 39
Nutrient Signaling and Lysosome Positioning Crosstalk Through a Multifunctional Protein, Folliculin
Garrido, N. D. M., & Aylett, C. H. S. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00108 · Cited by 37
Neuroinflammatory Gene Expression Alterations in Anterior Cingulate Cortical White and Gray Matter of Males With Autism Spectrum Disorder
Sciara, A., Beasley, B., Crawford, J. D., Anderson, E. P., Carrasco, T., Zheng, S., Ordway, G. A., & Chandley, M. (2020) · Autism Research · doi:10.1002/aur.2284 · Cited by 42

Authors: Tee, A. R., Fingar, D. C., Manning, B. D., Kwiatkowski, D. J., Cantley, L. C., & Blenis, J.
Affiliations: Brigham and Women's Hospital (US)
Corresponding author: Blenis, John
ORCID: Tee, Andrew R.
Fingar, Diane C.
Manning, Brendan D.
Kwiatkowski, David J.
Cantley, Lewis C.
Blenis, John
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2002-09-23
Volume: 99
Issue: 21
Pages: 13571-13576
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.202476899
PMC: PMC129715
OpenAlex: W2087812126
Cited by: 827
References: 31
Citations by year: 2026: 9 · 2025: 13 · 2024: 17 · 2023: 27 · 2022: 29 · 2021: 35 · 2020: 40 · 2019: 22 · 2018: 37 · 2017: 35 · 2016: 31 · 2015: 45 · 2014: 28 · 2013: 43 · 2012: 42
FWCI: 17.27
Type: journal article
Language: en
Update notices: correction (2021-08-09)
Open access: green
europepmc.org
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of General Medical Sciences (GM 41890, GM51405, R01GM056203, GM 56203, R01GM051405, R01GM041890, R37GM041890)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Health Sciences › Medicine › Genetics (clinical) › Tuberous Sclerosis Complex Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: tuberous sclerosis complex, TSC1, TSC2, hamartin, tuberin, mTOR signaling, 4E-BP1, S6K1, amino acid signaling, nutrient deprivation, rapamycin resistance, protein phosphorylation, eIF4E, tumor formation
MeSH terms: Tuberous Sclerosis Complex 1 Protein, Tuberous Sclerosis Complex 2 Protein, Amino Acids, Carrier Proteins, Cell Line, Humans, Insulin, Models, Biological, Phosphoproteins, Phosphorylation, Protein Kinases, Proteins, Repressor Proteins, Tuberous Sclerosis, Signal Transduction, Point Mutation, Cell Cycle Proteins, Phosphatidylinositol 3-Kinases, Ribosomal Protein S6 Kinases, Tumor Suppressor Proteins, Adaptor Proteins, Signal Transducing, TOR Serine-Threonine Kinases, In Vitro Techniques

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks