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Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling
Open accessAbstract
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.
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In the citing paper
“Loss of the TSC1–TSC2 protein complex leads to hyperactivation of mTOR complex 1 (mTORC1)18, a key signalling node that regulates cellular anabolic and catabolic processes19.”
From mTORC1 drives cell-autonomous astrocyte reactivity in tuberous sclerosis (2026) · cites this paper as [18]
In the citing paper
“The integration of the majority of external and survival signals feeding into the (m)TORC1 pathway occurs through the TSC complex (TSCC), composed of tuberous sclerosis complex protein 1 (TSC1) and TSC2, also known as hamartin and tuberin, and TBC1D7, which is the key signal integrator and negative regulator upstream of Rheb.”
From Signal integration in the (m)TORC1 growth pathway (2018) · cites this paper as Tee et al., 2002
In the citing paper
“This identification of this regulatory mechanism, shown using the human proteins, unequivocally identified TSC1-TSC2 as inhibitors of the mTORC1 signaling pathway (Inoki et al., 2002; Tee et al., 2002), specifically by virtue of TSC2 GAP activity toward the small GTPase Rheb (Castro et al., 2003; Garami et al., 2003; Inoki et al., 2003; Saucedo et al., 2003;”
From Signal integration in the (m)TORC1 growth pathway (2018) · cites this paper as Tee et al., 2002
Citations
Cites
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
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-citationRegulation 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
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
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-citationMammalian 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-citationMalignant 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
Kwiatkowski, D. J. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.5.525 · Cited by 674
Self-citationThe 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
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).
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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
PI3K-Akt pathway: Its functions and alterations in human cancer
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Fingar, D. C., & Blenis, J. (2004) · Oncogene · doi:10.1038/sj.onc.1207542 · Cited by 1,264
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Self-citationTee, 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
Self-citationPI3K/Akt and apoptosis: size matters
Franke, T. F., Hornik, C., Segev, L., Shostak, G. A., & Sugimoto, C. (2003) · Oncogene · doi:10.1038/sj.onc.1207115 · Cited by 1,195
Maira, S.-M., Stauffer, F., Brueggen, J., Furet, P., Schnell, C., Fritsch, C., Brachmann, S., Chène, P., De Pover, A., Schoemaker, K., et al. (2008) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-0017 · Cited by 1,134
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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
Wu, Y.-T., Tan, H.-L., Shui, G., Bauvy, C., Huang, Q., Wenk, M. R., Ong, C.-N., Codogno, P., & Shen, H.-M. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.080796 · Cited by 1,127
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Curatolo, P., Bombardieri, R., & Jóźwiak, S. (2008) · The Lancet · doi:10.1016/s0140-6736(08)61279-9 · Cited by 1,106
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Atkins, M. B., Hidalgo, M. M., Stadler, W. M., Logan, T. F., Dutcher, J. P., Hudes, G. R., Park, Y., Liou, S.-H., Marshall, B., Boni, J. P., et al. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.08.185 · Cited by 942
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Chen, L., Xu, B., Liu, L., Luo, Y., Zhou, H., Chen, W., Shen, T., Han, X., Kontos, C. D., & Huang, S. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.12.032 · Cited by 252
Wang, H., Kubica, N., Ellisen, L. W., Jefferson, L. S., & Kimball, S. R. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m610023200 · Cited by 262
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Metadata
- 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
- 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
- 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
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