Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40
Open accessAbstract
The mechanistic target of rapamycin complex 1 (mTORC1) controls cell growth and metabolism in response to nutrients, energy levels, and growth factors. It contains the atypical kinase mTOR and the RAPTOR subunit that binds to the Tor signalling sequence (TOS) motif of substrates and regulators. mTORC1 is activated by the small GTPase RHEB (Ras homologue enriched in brain) and inhibited by PRAS40. Here we present the 3.0 ångström cryo-electron microscopy structure of mTORC1 and the 3.4 ångström structure of activated RHEB-mTORC1. RHEB binds to mTOR distally from the kinase active site, yet causes a global conformational change that allosterically realigns active-site residues, accelerating catalysis. Cancer-associated hyperactivating mutations map to structural elements that maintain the inactive state, and we provide biochemical evidence that they mimic RHEB relieving auto-inhibition. We also present crystal structures of RAPTOR-TOS motif complexes that define the determinants of TOS recognition, of an mTOR FKBP12-rapamycin-binding (FRB) domain-substrate complex that establishes a second substrate-recruitment mechanism, and of a truncated mTOR-PRAS40 complex that reveals PRAS40 inhibits both substrate-recruitment sites. These findings help explain how mTORC1 selects its substrates, how its kinase activity is controlled, and how it is activated by cancer-associated mutations.
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Cross-linking of mTORC1 in the presence of RhebGTPgS and 4EBP1 yielded the cryo-EM structure of mTORC1 bound to Rheb.
“Cross-linking of mTORC1 in the presence of RhebGTPgS and 4EBP1, another well-known mTORC1 substrate (Burnett et al., 1998), yielded the cryo-EM structure of mTORC1 bound to Rheb (Yang et al., 2017).”
From Signal integration in the (m)TORC1 growth pathway (2018) · cites this paper as Yang et al., 2017
Density corresponding to Rheb was observed at the N-terminal portions of the N-HEAT, M-HEAT and FAT domains, resulting in a four-way interface where Rheb switch I residues bound the M-HEAT solenoid and FAT domain, and switch II formed contacts with all three mTORC1 domains.
“Density corresponding to Rheb was observed at the N-terminal portions of the N- HEAT, M-HEAT and FAT domains, thereby resulting in a four-way interface where Rheb switch I residues bound the M-HEAT solenoid and FAT domain, and switch II formed contacts with all three mTORC1 domains.”
From Signal integration in the (m)TORC1 growth pathway (2018) · cites this paper as Yang et al., 2017
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UCSF Chimera—A visualization system for exploratory research and analysis
Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., & Ferrin, T. E. (2004) · Journal of Computational Chemistry · doi:10.1002/jcc.20084 · Cited by 45,260 · see citing works
[20] Processing of X-ray diffraction data collected in oscillation mode
Otwinowski, Z., & Minor, W. (1997) · Methods in Enzymology · doi:10.1016/s0076-6879(97)76066-x · Cited by 33,475 · see citing works
<i>PHENIX</i> : a comprehensive Python-based system for macromolecular structure solution
Adams, P. D., Afonine, P. V., Bunkóczi, G., Chen, V. B., Davis, I. W., Echols, N., Headd, J. J., Hung, L.-W., Kapral, G. J., Grosse-Kunstleve, R. W., et al. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909052925 · Cited by 23,716 · see citing works
Jones, T. A., Zou, J.-Y., Cowan, S. W., & Kjeldgaard, M. (1991) · Acta Crystallographica Section A Foundations of Crystallography · doi:10.1107/s0108767390010224 · Cited by 12,650 · see citing works
Overview of the <i>CCP</i> 4 suite and current developments
Winn, M. D., Ballard, C. C., Cowtan, K. D., Dodson, E. J., Emsley, P., Evans, P. R., Keegan, R. M., Krissinel, E. B., Leslie, A. G. W., McCoy, A., et al. (2011) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910045749 · Cited by 12,353 · see citing works
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 · see citing works
MotionCor2 - anisotropic correction of beam-induced motion for improved cryo-electron microscopy
Zheng, S., Palovcak, E. J., Armache, J., Verba, K., Cheng, Y.-F., & Agard, D. (2017) · Nature Methods · doi:10.1038/nmeth.4193 · Cited by 7,678 · see citing works
PHENIX: a comprehensive Python-based system for macromolecular structure solution
Adams, P. D., Afonine, P. V., Bunkòczi, G., Chen, V. B., Davis, I., Echols, N., Headd, J. J., Hung, L., Kapral, G. J., Grosse‐Kunstleve, R. W., et al. (2012) · International Tables for Crystallography · doi:10.1107/97809553602060000865 · Cited by 7,334 · see citing works
Electrostatics of nanosystems: Application to microtubules and the ribosome
Baker, N., Sept, D., Joseph, S., Holst, M., & McCammon, J. A. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.181342398 · Cited by 7,125 · see citing works
RELION: Implementation of a Bayesian approach to cryo-EM structure determination
Scheres, S. H. W. (2012) · Journal of Structural Biology · doi:10.1016/j.jsb.2012.09.006 · Cited by 5,446 · see citing works
CTFFIND4: Fast and accurate defocus estimation from electron micrographs
Rohou, A. L., & Grigorieff, N. (2015) · Journal of Structural Biology · doi:10.1016/j.jsb.2015.08.008 · Cited by 4,926 · see citing works
Kim, D.-H., Sarbassov, D., Ali, S. M., King, J. E., Latek, R., Erdjument-Bromage, H., Tempst, P., & Sabatini, D. (2002) · Cell · doi:10.1016/s0092-8674(02)00808-5 · Cited by 3,135 · see citing works
Molecular mechanisms of mTOR-mediated translational control
Ma, X. M., & Blenis, J. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2672 · Cited by 2,558 · see citing works
Schägger, H. (2006) · Nature Protocols · doi:10.1038/nprot.2006.4 · Cited by 2,519 · see citing works
Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action.
Hara, K., Maruki, Y., Long, S., Yoshino, K., Oshiro, N., Hidayat, S., Tokunaga, C., Avruch, J., & Yonezawa, K. (2002) · Cell · doi:10.1016/s0092-8674(02)00833-4 · Cited by 1,916 · see citing works
Automated molecular microscopy: The new Leginon system
Suloway, C. J. M., Pulokas, J., Fellmann, D., Cheng, A., Guerra, F., Quispe, J. D., Stagg, S. M., Potter, C. S., & Carragher, B. O. (2005) · Journal of Structural Biology · doi:10.1016/j.jsb.2005.03.010 · Cited by 1,681 · see citing works
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 1,358 · see citing works
Prevention of overfitting in cryo-EM structure determination
Scheres, S., & Chen, S. (2012) · Nature Methods · doi:10.1038/nmeth.2115 · Cited by 1,311 · see citing works
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 · see citing works
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. W., 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 1,233 · see citing works
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 1,185 · see citing works
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 1,139 · see citing works
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 · see citing works
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 · see citing works
Self-citationKim, 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 955 · see citing works
Structure of the FKBP12-Rapamycin Complex Interacting with Binding Domain of Human FRAP
Choi, J., Chen, J., Schreiber, S. L., & Clardy, J. (1996) · Science · doi:10.1126/science.273.5272.239 · Cited by 933 · see citing works
Accelerated cryo-EM structure determination with parallelisation using GPUs in RELION-2
Kimanius, D., Forsberg, B. O., Scheres, S. H. W., & Lindahl, E. R. (2016) · eLife · doi:10.7554/elife.18722 · Cited by 903 · see citing works
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 855 · see citing works
Regulation of mTORC1 by amino acids
Bar-Peled, L., & Sabatini, D. M. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.03.003 · Cited by 773 · see citing works
Regulation of mTORC1 by PI3K Signaling
Dibble, C. C., & Cantley, L. (2015) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.06.002 · Cited by 770 · see citing works
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 · see citing works
Rheb promotes cell growth as a component of the insulin/TOR signalling network
Saucedo, L. J., Gao, X., Chiarelli, D. A., Li, L., Pan, D., & Edgar, B. A. (2003) · Nature Cell Biology · doi:10.1038/ncb996 · Cited by 658 · see citing works
mTORC1 signaling and the metabolic control of cell growth
Ben‐Sahra, I., & Manning, B. D. (2017) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2017.02.012 · Cited by 641 · see citing works
Tools for macromolecular model building and refinement into electron cryo-microscopy reconstructions
Brown, A., Long, F., Nicholls, R. A., Toots, J., Emsley, P., & Murshudov, G. N. (2014) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s1399004714021683 · Cited by 621 · see citing works
Processing of Structurally Heterogeneous Cryo-EM Data in RELION
Scheres, S. H. W. (2016) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/bs.mie.2016.04.012 · Cited by 550 · see citing works
Rheb is an essential regulator of S6K in controlling cell growth in Drosophila
Stocker, H., Radimerski, T., Schindelholz, B., Wittwer, F., Belawat, P., Daram, P., Breuer, S., Thomas, G., & Hafen, E. (2003) · Nature Cell Biology · doi:10.1038/ncb995 · Cited by 530 · see citing works
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 · see citing works
Cap-Dependent Translation Initiation in Eukaryotes Is Regulated by a Molecular Mimic of eIF4G
Marcotrigiano, J., Gingras, A., Sonenberg, N., & Burley, S. K. (1999) · Molecular Cell · doi:10.1016/s1097-2765(01)80003-4 · Cited by 512 · see citing works
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 512 · see citing works
PRAS40 Regulates mTORC1 Kinase Activity by Functioning as a Direct Inhibitor of Substrate Binding
Wang, L., Harris, T. E., Roth, R. A., & Lawrence, J. C. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702376200 · Cited by 491 · see citing works
mTORC1 Phosphorylation Sites Encode Their Sensitivity to Starvation and Rapamycin
Kang, S. A. W., 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 432 · see citing works
Grabiner, B., Nardi, V., Birsoy, K., Possemato, R., Shen, K., Sinha, S., Jordan, A. A., Beck, A. H., & Sabatini, D. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0929 · Cited by 418 · see citing works
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 · see citing works
Beam-induced motion correction for sub-megadalton cryo-EM particles
Scheres, S. H. W. (2014) · eLife · doi:10.7554/elife.03665 · Cited by 341 · see citing works
Oshiro, N., Takahashi, R., Yoshino, K., Tanimura, K., Nakashima, A., Eguchi, S., Miyamoto, T., Hara, K., Takehana, K., Avruch, J., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702636200 · Cited by 318 · see citing works
Wagle, N., Grabiner, B. C., Allen, E. M. V., Hodis, E., Jacobus, S. J., Supko, J. G., Stewart, M. L., Choueiri, T. K., Gandhi, L., Cleary, J. M., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0353 · Cited by 281 · see citing works
Conformation-independent structural comparison of macromolecules withProSMART
Nicholls, R. A., Fischer, M. M., McNicholas, S. J., & Murshudov, G. N. (2014) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s1399004714016241 · Cited by 187 · see citing works
Urano, J., Sato, T., Matsuo, T., Otsubo, Y., Yamamoto, M. P., & Tamanoi, F. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0608510104 · Cited by 140 · see citing works
4.4 Å Resolution Cryo-EM structure of human mTOR Complex 1
Yang, H., Wang, J., Liu, M., Chen, X., Huang, M., Tan, D., Wong, C. C. L., Wang, J., Wang, J., Xu, Y., et al. (2016) · Protein & Cell · doi:10.1007/s13238-016-0346-6 · Cited by 96 · see citing works
Self-citationStructural Basis for the Unique Biological Function of Small GTPase RHEB
Yu, Y., Li, S., Xu, X., Li, Y., Guan, K., Arnold, E., & Ding, J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501253200 · Cited by 89 · see citing works
Tor forms a dimer through an N-terminal helical solenoid with a complex topology
Baretić, D., Berndt, A., Ohashi, Y., Johnson, C. M., & Williams, R. L. (2016) · Nature Communications · doi:10.1038/ncomms11016 · Cited by 80 · see citing works
Isolation of Hyperactive Mutants of Mammalian Target of Rapamycin
Ohne, Y., Takahara, T., Hatakeyama, R., Matsuzaki, T., Noda, M., Mizushima, N., & Maeda, T. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m801546200 · Cited by 70 · see citing works
Michels, A. A. (2011) · Biochemical Society Transactions · doi:10.1042/bst0390487 · Cited by 35 · see citing works
Evaluating PI3 Kinase Isoforms Using Transcreener™ ADP Assays
Klink, T. A., Kleman-Leyer, K. M., Kopp, A. L., Westermeyer, T. A., & Lowery, R. G. (2008) · SLAS DISCOVERY · doi:10.1177/1087057108319864 · Cited by 32 · see citing works
Raptor protein contains a caspase-like domain
Ginalski, K., ZHANG, H., & Grishin, N. V. (2004) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2004.08.006 · Cited by 25 · see citing works
Flagged first, then by citations
Research works printed but not linked: 5
- [1]Yang H mTOR kinase structure, mechanism and regulation Nature 497 217 223 2013 23636326 PMC4512754
- [2]Choi J Chen J Schreiber SL Clardy J Structure of the FKBP12-rapamycin complex interacting with the binding domain of human FRAP Science 273 239 242 1996 8662507
- [4]Brown A Tools for macromolecular model building and refinement into electron cryo-microscopy reconstructions Acta Crystallogr D Biol Crystallogr 71 136 153 2015 25615868 PMC4304694
- [5]Kim DH mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery Cell 110 163 175 2002 12150925
- [6]Grabiner BC A diverse array of cancer-associated MTOR mutations are hyperactivating and can predict rapamycin sensitivity Cancer discovery 4 554 563 2014 24631838 PMC4012430
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mTOR at the nexus of nutrition, growth, ageing and disease
Liu, G. Y., & Sabatini, D. M. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0199-y · Cited by 2,737 · see citing works
PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer
Glaviano, A., Foo, A. S. C., Lam, H. Y., Yap, K. C. H., Jacot, W., Jones, R. H., Eng, H., Nair, M. G., Makvandi, P., Geoerger, B., et al. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01827-6 · Cited by 2,138 · see citing works
mTOR signalling and cellular metabolism are mutual determinants in cancer
Mossmann, D., Park, S., & Hall, M. N. (2018) · Nature reviews. Cancer · doi:10.1038/s41568-018-0074-8 · Cited by 1,088 · see citing works
mTOR as a central hub of nutrient signalling and cell growth
Kim, J., & Guan, K. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0205-1 · Cited by 1,067 · see citing works
The lysosome as a cellular centre for signalling, metabolism and quality control
Lawrence, R. E., & Zoncu, R. (2019) · Nature Cell Biology · doi:10.1038/s41556-018-0244-7 · Cited by 920 · see citing works
Regulation and metabolic functions of mTORC1 and mTORC2.
Szwed, A., Kim, E., & Jacinto, E. (2021) · Physiological Reviews · doi:10.1152/physrev.00026.2020 · Cited by 723 · see citing works
AMPK and TOR: The Yin and Yang of Cellular Nutrient Sensing and Growth Control
González, A., Hall, M. N., Lin, S.-C., & Hardie, D. G. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.01.015 · Cited by 797 · see citing works
Molecular mechanisms of dietary restriction promoting health and longevity
Green, C. L., Lamming, D. W., & Fontana, L. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00411-4 · Cited by 714 · see citing works
mTOR: Role in cancer, metastasis and drug resistance
Murugan, A. K. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.07.003 · Cited by 483 · see citing works
mTOR as a central regulator of lifespan and aging
Papadopoli, D. J., Boulay, K., Kazak, L., Pollak, M., Mallette, F. A., Topisirović, I., & Hulea, L. (2019) · F1000Research · doi:10.12688/f1000research.17196.1 · Cited by 431 · see citing works
mTOR substrate phosphorylation in growth control.
Battaglioni, S., Benjamin, D., Wälchli, M., Maier, T., & Hall, M. (2022) · Cell · doi:10.1016/j.cell.2022.04.013 · Cited by 388 · see citing works
Targeting the biology of aging with mTOR inhibitors
Mannick, J. B., & Lamming, D. W. (2023) · Nature Aging · doi:10.1038/s43587-023-00416-y · Cited by 372 · see citing works
Autophagy and Autophagy-Related Diseases: A Review
Ichimiya, T., Yamakawa, T., Hirano, T., Yokoyama, Y., Hayashi, Y., Hirayama, D., Wagatsuma, K., Itoi, T., & Nakase, H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21238974 · Cited by 338 · see citing works
A substrate-specific mTORC1 pathway underlies Birt–Hogg–Dubé syndrome
Napolitano, G., Malta, C. D., Esposito, A., de Araujo, M. E. G., Pece, S., Bertalot, G., Matarese, M., Benedetti, V., Zampelli, A., Stasyk, T., et al. (2020) · Nature · doi:10.1038/s41586-020-2444-0
Signaling Pathways Involved in the Regulation of mRNA Translation
Roux, P. P., & Topisirović, I. (2018) · Molecular and Cellular Biology · doi:10.1128/mcb.00070-18 · Cited by 314 · see citing works
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 295 · see citing works
Amino acid-dependent control of mTORC1 signaling: a variety of regulatory modes
Takahara, T., Amemiya, Y., Sugiyama, R., Maki, M., & Shibata, H. (2020) · Journal of Biomedical Science · doi:10.1186/s12929-020-00679-2 · Cited by 300 · see citing works
Cellular functions of the protein kinase ATM and their relevance to human disease
Lee, J., & Paull, T. T. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00394-2 · Cited by 290 · see citing works
Goul, C., Peruzzo, R., & Zoncu, R. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00641-8 · Cited by 269 · see citing works
Capturing the phosphorylation and protein interaction landscape of the plant TOR kinase
Leene, J. V., Han, C., Gadeyne, A., Eeckhout, D., Matthijs, C., Cannoot, B., Winne, N. D., Persiau, G., Slijke, E. V. D., van de Cotte, B., et al. (2019) · Nature Plants · doi:10.1038/s41477-019-0378-z · Cited by 269 · see citing works
Jhanwar-Uniyal, M., Wainwright, J. V., Mohan, A. L., Tobias, M. E., Murali, R., Gandhi, C. D., & Schmidt, M. H. (2019) · Advances in Biological Regulation · doi:10.1016/j.jbior.2019.03.003 · Cited by 268 · see citing works
Li, L., Liu, X., Sanders, K. L., Edwards, J. L., Ye, J., Si, F., Gao, A., Huang, L., Hsueh, E. C., Ford, D. A., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.09.020 · Cited by 247 · see citing works
Glutamine and asparagine activate mTORC1 independently of Rag GTPases
Meng, D.-L., Yang, Q., Wang, H., Melick, C. H., Navlani, R., Frank, A., & Jewell, J. L. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ac119.011578 · Cited by 192 · see citing works
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AMPK directly activates mTORC2 to promote cell survival during acute energetic stress
Kazyken, D., Magnuson, B., Bodur, Ç., Acosta-Jaquez, H. A., Zhang, D., Tong, X., Barnes, T. M., Steinl, G. K., Patterson, N., Altheim, C. H., et al. (2019) · Science Signaling · doi:10.1126/scisignal.aav3249 · Cited by 221 · see citing works
Structural basis for the docking of mTORC1 on the lysosomal surface
Rogala, K. B., Gu, X., Kedir, J. F., Abu-Remaileh, M., Bianchi, L. F., Bottino, A. M. S., Dueholm, R., Niehaus, A., Overwijn, D., Fils, A.-C. P., et al. (2019) · Science · doi:10.1126/science.aay0166 · Cited by 191 · see citing works
Structure of the lysosomal mTORC1–TFEB–Rag–Ragulator megacomplex
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Lysosome: The metabolic signaling hub
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mTORC1 and Nutrient Homeostasis: The Central Role of the Lysosome
Rabanal-Ruiz, Y., & Korolchuk, V. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19030818 · Cited by 159 · see citing works
Regulation of Body Size and Growth Control
Texada, M., Koyama, T., & Rewitz, K. (2020) · Genetics · doi:10.1534/genetics.120.303095 · Cited by 129 · see citing works
The role of lysosomes in cancer development and progression
Tang, T., Yang, Z.-Y., Wang, D., Yang, X., Wang, J., Li, L., Wen, Q., Gao, L., Bian, X., & Yu, S.-C. (2020) · Cell & Bioscience · doi:10.1186/s13578-020-00489-x · Cited by 145 · see citing works
The central moTOR of metabolism
Simcox, J., & Lamming, D. W. (2022) · Developmental Cell · doi:10.1016/j.devcel.2022.02.024 · Cited by 162 · see citing works
Structural basis of homologous recombination
Sun, Y., McCorvie, T. J., Yates, L. A., & Zhang, X. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03365-1 · Cited by 160 · see citing works
Metabolic reprogramming, sensing, and cancer therapy
Mao, Y., Xia, Z., Xia, W., & Jiang, P. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.115064 · Cited by 168 · see citing works
The Functional Proximal Proteome of Oncogenic Ras Includes mTORC2
Kovalski, J. R., Bhaduri, A., Zehnder, A. M., Neela, P. H., Che, Y., Wozniak, G. G., & Khavari, P. A. (2019) · Molecular Cell · doi:10.1016/j.molcel.2018.12.001 · Cited by 154 · see citing works
Architecture of human Rag GTPase heterodimers and their complex with mTORC1
Anandapadamanaban, M., Masson, G., Perisic, O., Berndt, A., Kaufman, J., Johnson, C. M., Santhanam, B., Rogala, K. B., Sabatini, D., & Williams, R. L. (2019) · Science · doi:10.1126/science.aax3939 · Cited by 124 · see citing works
A small-molecule PI3Kα activator for cardioprotection and neuroregeneration
Gong, G. Q., Bilanges, B., Allsop, B., Masson, G. R., Roberton, V. H., Askwith, T., Oxenford, S. J., Madsen, R. R., Conduit, S. E., Bellini, D., et al. (2023) · Nature · doi:10.1038/s41586-023-05972-2 · Cited by 151 · see citing works
A multi-omic single-cell landscape of human gynecologic malignancies
Regner, M. J., Wiśniewska, K., García‐Recio, S., Thennavan, A., Méndez-Giráldez, R., Malladi, V. S., Hawkins, G. M., Parker, J. S., Perou, C. M., Bae-Jump, V. L., et al. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.10.013 · Cited by 139 · see citing works
Non-canonical mTORC1 signaling at the lysosome.
Napolitano, G., Malta, C. D., & Ballabio, A. (2022) · Trends in Cell Biology · doi:10.1016/j.tcb.2022.04.012 · Cited by 125 · see citing works
How Lysosomes Sense, Integrate, and Cope with Stress
Säftig, P., & Puertollano, R. (2020) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2020.09.004 · Cited by 135 · see citing works
Roles of mTOR Signaling in Tissue Regeneration
Wei, X., Luo, L., & Chen, J.-Z. (2019) · Cells · doi:10.3390/cells8091075 · Cited by 132 · see citing works
Cryo-EM structure of the human FLCN-FNIP2-Rag-Ragulator complex
Shen, K., Rogala, K. B., Chou, H., Huang, R. K., Yu, Z.-H., & Sabatini, D. (2019) · Cell · doi:10.1016/j.cell.2019.10.036 · Cited by 111 · see citing works
Cryo-EM structure of human mTOR complex 2
Chen, X., Liu, M., Tian, Y., Li, J., Qi, Y., Zhao, D., Wu, Z., Huang, M., Wong, C. C. L., Wang, H., et al. (2018) · Cell Research · doi:10.1038/s41422-018-0029-3 · Cited by 131 · see citing works
Self-citationStructure of an activated DNA-PK and its implications for NHEJ
Chen, X., Xu, X., Chen, Y., Cheung, J. C. Y., Wang, H., Jiang, J., de Val, N., Fox, T. L., Gellert, M. F., & Yang, W. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.12.015 · Cited by 132 · see citing works
Spatially Distinct Pools of TORC1 Balance Protein Homeostasis
Hatakeyama, R., Gulli, M., Hu, Z., Jaquenoud, M., Osuna, G. M. G., Sardu, A., Dengjel, J., & VIRGILIO, C. D. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.10.040 · Cited by 124 · see citing works
Eukaryotic translation initiation factors as promising targets in cancer therapy
Hao, P., Yu, J.-J., Ward, R., Liu, Y., Hao, Q., An, S., & Xu, T.-R. (2020) · Cell Communication and Signaling · doi:10.1186/s12964-020-00607-9 · Cited by 95 · see citing works
The Lysosome at the Intersection of Cellular Growth and Destruction
Shin, H. R., & Zoncu, R. (2020) · Developmental Cell · doi:10.1016/j.devcel.2020.06.010 · Cited by 112 · see citing works
The dynamic mechanism of 4E-BP1 recognition and phosphorylation by mTORC1
Böhm, R., Imseng, S., Jakob, R. P., Hall, M. N., Maier, T., & Hiller, S. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.03.031 · Cited by 106 · see citing works
The 3.2-Å resolution structure of human mTORC2
Scaiola, A., Mangia, F., Imseng, S., Boehringer, D., Berneiser, K., Shimobayashi, M., Stuttfeld, E., Hall, M. N., Ban, N., & Maier, T. (2020) · Science Advances · doi:10.1126/sciadv.abc1251 · Cited by 104 · see citing works
Lawrence, R., Cho, K., Rappold, R., Thrun, A., Tofaute, M., Kim, D. J., Moldavski, O., Hurley, J., & Zoncu, R. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0148-6 · Cited by 96 · see citing works
Guo, Y., Zhu, X., Zeng, M., Qi, L., Tang, X., Wang, D., Zhang, M., Xie, Y., Li, H., Yang, X., et al. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01443-2 · Cited by 104 · see citing works
Regulation of mTORC1 by Upstream Stimuli
Melick, C. H., & Jewell, J. L. (2020) · Genes · doi:10.3390/genes11090989 · Cited by 80 · see citing works
<scp>mTOR</scp> signaling and Alzheimer's disease: What we know and where we are?
Davoody, S., Asgari Taei, A., Khodabakhsh, P., & Dargahi, L. (2024) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14463 · Cited by 96 · see citing works
Gillingham, A. K., Bertram, J., Begum, F., & Munro, S. (2019) · eLife · doi:10.7554/elife.45916 · Cited by 96 · see citing works
A small molecule inhibitor of Rheb selectively targets mTORC1 signaling
Mahoney, S. J., Narayan, S., Molz, L., Berstler, L. A., Kang, S. A. W., Vlasuk, G. P., & Saiah, E. (2018) · Nature Communications · doi:10.1038/s41467-018-03035-z · Cited by 95 · see citing works
Mitochondrial and metabolic alterations in cancer cells
Gregorio, J. D., Petricca, S., Iorio, R., Toniato, E., & Flati, V. (2022) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2022.151225 · Cited by 93 · see citing works
Searching for the link between inflammaging and sarcopenia
Wang, T. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101611 · Cited by 88 · see citing works
New insights into no-go, non-stop and nonsense-mediated mRNA decay complexes
Powers, K. T., Szeto, J.-Y. A., & Schaffitzel, C. (2020) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2020.06.011 · Cited by 84 · see citing works
mTOR in programmed cell death and its therapeutic implications.
Xie, Y., Lei, X., Zhao, G.-Y., Guo, R., & Cui, N. (2023) · Cytokine & growth factor reviews · doi:10.1016/j.cytogfr.2023.06.002 · Cited by 72 · see citing works
Mutvei, A. P., Nagiec, M. J., Hamann, J. C., Kim, S. G., Vincent, C. T., & Blenis, J. (2020) · Nature Communications · doi:10.1038/s41467-020-15156-5 · Cited by 79 · see citing works
Autophosphorylation transforms DNA-PK from protecting to processing DNA ends
Liu, L., Chen, X., Li, J., Wang, H., Buehl, C. J., Goff, N. J., Meek, K., Yang, W., & Gellert, M. F. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.11.025 · Cited by 80 · see citing works
Structural and functional analysis of the role of the chaperonin CCT in mTOR complex assembly
Cuéllar, J., Ludlam, W. G., Tensmeyer, N. C., Aoba, T., Dhavale, M., Santiago, C. A., Bueno-Carrasco, M. T., Mann, M. J., Plimpton, R. L., Makaju, A., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10781-1 · Cited by 77 · see citing works
The post‐translational regulation of transcription factor EB (TFEB) in health and disease
Takla, M., Keshri, S., & Rubinsztein, D. C. (2023) · EMBO Reports · doi:10.15252/embr.202357574 · Cited by 73 · see citing works
Burnett, G. L., Yang, Y. C., Aggen, J. B., Pitzen, J., Gliedt, M. K., Semko, C. M., Marquez, A., Evans, J. W., Wang, G., Won, W. S., et al. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c01658 · Cited by 72 · see citing works
Critical role of mTOR in regulating aerobic glycolysis in carcinogenesis (Review)
Fan, H. J., Wu, Y., Yu, S., Li, X., Wang, A., Wang, S., Chen, W., & Lu, Y. (2020) · International Journal of Oncology · doi:10.3892/ijo.2020.5152 · Cited by 72 · see citing works
Trautman, M. E., Richardson, N. E., & Lamming, D. W. (2022) · Aging Cell · doi:10.1111/acel.13626 · Cited by 67 · see citing works
The tRNA-GCN2-FBXO22-axis-mediated mTOR ubiquitination senses amino acid insufficiency.
Ge, M.-K., Zhang, C., Zhang, N., He, P., Cai, H.-Y., Li, S., Wu, S., Chu, X.-L., Zhang, Y.-X., Ma, H.-M., et al. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.10.016 · Cited by 69 · see citing works
Weak membrane interactions allow Rheb to activate mTORC1 signaling without major lysosome enrichment
Angarola, B., & Ferguson, S. (2019) · bioRxiv · doi:10.1091/mbc.e19-03-0146 · Cited by 58 · see citing works
Evolutionarily divergent mTOR remodels translatome for tissue regeneration
Zhulyn, O., Rosenblatt, H. D., Shokat, L., Dai, S. A., Kuzuoğlu‐Öztürk, D., Zhang, Z., Ruggero, D., Shokat, K. M., & Barna, M. (2023) · Nature · doi:10.1038/s41586-023-06365-1 · Cited by 67 · see citing works
Germline and sporadic mTOR pathway mutations in low-grade oncocytic tumor of the kidney
Kapur, P., Gao, M., Zhong, H., Chintalapati, S., Mitui, M., Barnes, S. D., Zhou, Q., Miyata, J., Carrillo, D., Malladi, V. S., et al. (2021) · Modern Pathology · doi:10.1038/s41379-021-00896-6 · Cited by 65 · see citing works
Regulation of mTOR by phosphatidic acid
Frias, M. A., Hatipoglu, A., & Foster, D. A. (2023) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2023.01.004 · Cited by 63 · see citing works
Autophagy Function and Dysfunction: Potential Drugs as Anti-Cancer Therapy
Cuomo, F., Altucci, L., & Cobellis, G. (2019) · Cancers · doi:10.3390/cancers11101465 · Cited by 62 · see citing works
The complex network of mTOR signaling in the heart.
Sciarretta, S., Forte, M., Frati, G., & Sadoshima, J. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvab033 · Cited by 58 · see citing works
Snf1/AMPK fine-tunes TORC1 signaling in response to glucose starvation
Caligaris, M., Nicastro, R., Hu, Z.-H., Tripodi, F., Hummel, J., Pillet, B., Deprez, M., Winderickx, J., Rospert, S., Coccetti, P., et al. (2022) · bioRxiv · doi:10.7554/elife.84319 · Cited by 44 · see citing works
TSC1 binding to lysosomal PIPs is required for TSC complex translocation and mTORC1 regulation
Fitzian, K., Brückner, A., Brohée, L., Zech, R., Antoni, C., Kiontke, S., Gasper, R., Matos, A. L. L., Beel, S., Wilhelm, S., et al. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.04.019 · Cited by 60 · see citing works
Architecture and activation of phosphatidylinositol 3-kinase related kinases
Imseng, S., Aylett, C. H. S., & Maier, T. (2018) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2018.03.010 · Cited by 60 · see citing works
Signal Transduction: Magnesium Manifests as a Second Messenger
Stangherlin, A., & O'Neill, J. S. (2018) · Current Biology · doi:10.1016/j.cub.2018.11.003 · Cited by 59 · see citing works
Phospholipase D as a key modulator of cancer progression
Yao, Y., Wang, X., Li, H., Fan, J., Qian, X., Li, H., & Xu, Y. (2020) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/brv.12592 · Cited by 58 · see citing works
Clinically Precedented Protein Kinases: Rationale for Their Use in Neurodegenerative Disease
Benn, C., & Dawson, L. A. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.00242 · Cited by 57 · see citing works
Mitochondrial-encoded MOTS-c prevents pancreatic islet destruction in autoimmune diabetes
Kong, B. S., Min, S. H., Lee, C. D., & Cho, Y. M. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109447 · Cited by 62 · see citing works
TFEB drives mTORC1 hyperactivation and kidney disease in Tuberous Sclerosis Complex
Alesi, N., Khabibullin, D., Rosenthal, D. M., Akl, E. W., Cory, P. M., Alchoueiry, M., Salem, S., Daou, M., Gibbons, W. F., Chen, J. A., et al. (2024) · Nature Communications · doi:10.1038/s41467-023-44229-4 · Cited by 58 · see citing works
Structure of the human ATM kinase and mechanism of Nbs1 binding
Warren, C., & Pavletich, N. P. (2022) · eLife · doi:10.7554/elife.74218 · Cited by 56 · see citing works
Self-citationResistance Exercise-Induced Hypertrophy: A Potential Role for Rapamycin-Insensitive mTOR
Ogasawara, R., Jensen, T. E., Goodman, C. A., & Hornberger, T. A. (2019) · Exercise and Sport Sciences Reviews · doi:10.1249/jes.0000000000000189 · Cited by 56 · see citing works
Regulation of mTORC1 by Small GTPases in Response to Nutrients.
Zhu, M., & Wang, X.-Q. (2020) · Journal of NutriLife · doi:10.1093/jn/nxz301 · Cited by 37 · see citing works
Next generation strategies for geroprotection via mTORC1 inhibition.
Dumas, S., & Lamming, D. (2019) · The journals of gerontology. Series A, Biological sciences and medical sciences · doi:10.1093/gerona/glz056 · Cited by 38 · see citing works
Rethinking glutamine metabolism and the regulation of glutamine addiction by oncogenes in cancer
Ni, R., Li, Z., Li, L., Peng, D., Ming, Y., Li, L., & Liu, Y. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1143798 · Cited by 55 · see citing works
mTOR Signaling in Metabolic Stress Adaptation
Wu, C., & Storey, K. B. (2021) · Biomolecules · doi:10.3390/biom11050681 · Cited by 51 · see citing works
Kciuk, M., Mujwar, S., Szymanowska, A., Marciniak, B., Bukowski, K., Mojzych, M., & Kontek, R. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23115892 · Cited by 51 · see citing works
Contemporary mTOR inhibitor scaffolds to diseases breakdown: A patent review (2015–2021)
Olekšák, P., Nepovimová, E., Chrienová, Ž., Musílek, K., Patočka, J., & Kuča, K. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114498 · Cited by 52 · see citing works
Taurine from tumour niche drives glycolysis to promote leukaemogenesis
Sharma, S., Rodems, B. J., Baker, C. D., Kaszuba, C. M., Franco, E. I., Smith, B. R., Ito, T., Swovick, K., Welle, K. A., Zhang, Y., et al. (2025) · Nature · doi:10.1038/s41586-025-09018-7 · Cited by 53 · see citing works
Baicalein and Baicalin Promote Melanoma Apoptosis and Senescence via Metabolic Inhibition
Huang, L., Peng, B., Nayak, Y. R., Wang, C., Si, F., Liu, X., Dou, J., Xu, H., & Peng, G. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00836 · Cited by 51 · see citing works
The TSC Complex-mTORC1 Axis: From Lysosomes to Stress Granules and Back
Rehbein, U., Prentzell, M. T., Sandoval, M. C., Heberle, A. M., Henske, E. P., Opitz, C. A., & Thedieck, K. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.751892 · Cited by 51 · see citing works
Does Ras Activate Raf and PI3K Allosterically?
Nussinov, R., Tsai, C., & Jang, H. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.01231 · Cited by 50 · see citing works
Therapeutic Targeting of mTOR in T-Cell Acute Lymphoblastic Leukemia: An Update
Evangelisti, C., Chiarini, F., McCubrey, J. A., & Martelli, A. M. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19071878 · Cited by 50 · see citing works
Ceska, T., Chung, C., Cooke, R., Phillips, C., & Williams, P. A. (2019) · Biochemical Society Transactions · doi:10.1042/bst20180267 · Cited by 50 · see citing works
Insulin Regulation of Hepatic Lipid Homeostasis
Uehara, K., Santoleri, D., Whitlock, A. E. G., & Titchenell, P. M. (2023) · Comprehensive Physiology · doi:10.1002/cphy.c220015 · Cited by 49 · see citing works
Comparative evaluation of methods for the prediction of protein–ligand binding sites
Utgés, J. S., & Barton, G. J. (2024) · Journal of Cheminformatics · doi:10.1186/s13321-024-00923-z · Cited by 49 · see citing works
Combining mTOR Inhibitors and T Cell-Based Immunotherapies in Cancer Treatment
Hage, A., & Dormond, O. (2021) · Cancers · doi:10.3390/cancers13061359 · Cited by 49 · see citing works
Yang, M., Hu, M. X., Zhang, Y., Jia, S., Sun, X., Zhao, W., Ge, M., & Dong, B. (2022) · BMC Geriatrics · doi:10.1186/s12877-022-03617-z · Cited by 48 · see citing works
Dinotefuran exposure induces autophagy and apoptosis through oxidative stress in Bombyx mori
Lu, Q., Xu, S., Hao, Z., Li, Y., Huang, Y., Ying, S., Jing, W., Zou, S., Xu, Y., & Wang, H. (2023) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2023.131997 · Cited by 48 · see citing works
- Authors
- Yang, H., Jiang, X., Li, B., Yang, H. J., Miller, M., Yang, A., Dhar, A., & Pavletich, N. P.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Pavletich, Nikola P.
- Venue
- Nature
- Published
- 2017-12
- Volume
- 552
- Issue
- 7685
- Pages
- 368-373
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5750076
- OpenAlex
- W2773300145
- Cited by
- 548
- References
- 55
- Citations by year
- 2026: 55 · 2025: 65 · 2024: 68 · 2023: 66 · 2022: 63 · 2021: 80 · 2020: 74 · 2019: 53 · 2018: 23
- FWCI
- 16.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Memorial Sloan-Kettering Cancer Center (CA008748)
- National Institutes of Health (CA008748)
- National Cancer Institute (P30CA008748)
- National Institute of General Medical Sciences (P41GM103310, R01GM064644)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- mTORC1, Rheb, PRAS40, allosteric activation, allosteric inhibition, raptors, substrate recognition, cancer-associated mutations, mTOR hyperactivation, protein complex structure, cell growth regulation
- MeSH terms
- Protein Domains, Ras Homolog Enriched in Brain Protein, Mechanistic Target of Rapamycin Complex 1, Regulatory-Associated Protein of mTOR, Binding Sites, Enzyme Activation, Humans, Models, Molecular, Mutation, Neoplasms, Protein Binding, Substrate Specificity, Signal Transduction, Crystallography, X-Ray, Sirolimus, Catalytic Domain, Cryoelectron Microscopy, Amino Acid Motifs, Tacrolimus Binding Protein 1A, Ribosomal Protein S6 Kinases, 70-kDa, Adaptor Proteins, Signal Transducing, Biocatalysis
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