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A Tumor Suppressor Complex with GAP Activity for the Rag GTPases That Signal Amino Acid Sufficiency to mTORC1
Open accessAbstract
Limiting mTORC1: The mTORC1 protein kinase complex has important functions linking metabolism to cell growth and its functions are disrupted in common diseases, including cancer and diabetes. Bar-Peled et al. (p. 1100 ; see the Perspective by Shaw ) discovered regulatory components that help turn down signaling by mTORC1 when cells are deprived of amino acids. Two complexes of proteins, GATOR1 and GATOR2, have opposite effects on activity and cellular localization of mTORC1. Components of the GATOR1 complex negatively regulate mTORC1 and appear to function as tumor supressors. Cancers with loss of GATOR1 function may be particularly amenable to therapeutic strategies that limit activity of mTORC1.
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“These include CG12090, the Drosophila ortholog of mammalian DEPDC5, which was found to be part of the GATOR1 complex that inhibits the Tor pathway during the protracted course of our studies.”
From Functional unknomics: Systematic screening of conserved genes of unknown function (2023) · cites this paper as [54]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“WDR59 and WDR24 are both subunits of GATOR2 complex, which functions as a positive regulator of amino‐acid‐mediated mTORC1 activation (Bar‐Peled et al., 2013), and WDR24 modulates mTOR through the previously described changes in lysosome cellular positioning and dynamics (Korolchuk et al., 2011) and thus indirectly modulates autophagic flux (Cai et al., 2016).”
From Autophagy gene expression in skeletal muscle of older individuals is associated with physical performance, muscle volume and mitochondrial function in the study of muscle, mobility and aging ( SOMMA ) (2024) · cites this paper as Bar‐Peled et al., 2013
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“Mutants in GATOR1 subunits promote cell growth by increasing Tor activity [54,55].”
From Functional unknomics: Systematic screening of conserved genes of unknown function (2023) · cites this paper as [54]
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“At the Ragulator, the Rag heterodimer interacts with GATOR (GAP Activity Towards Rags), an octomeric complex that controls the activity of the Rag proteins [22].”
From Using Molecular Biology to Maximize Concurrent Training (2014) · cites this paper as [22]
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“One of the best described systems for regulating the nucleotide binding status of the Rag GTPases is the activity of the GATOR complexes. GATOR1 functions as a GAP for RagA and RagB, while GATOR2 acts to inhibit the activity of GATOR1 167,168.”
From Targeting the biology of aging with mTOR inhibitors (2023) · cites this paper as [168]
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“One of the best described systems for regulating the nucleotide binding status of the Rag GTPases is the activity of the GATOR complexes. GATOR1 functions as a GAP for RagA and RagB, while GATOR2 acts to inhibit the activity of GATOR1 167,168.”
From Targeting the biology of aging with mTOR inhibitors (2023) · cites this paper as [168]
In the citing paper
“Upstream regulation of the Rag GTPases is more baroque, featuring at least four large protein complexes including: GATOR1, a GAP for RagA/RagB/Gtr1 (Neklesa and Davis, 2009; Bar-Peled et al., 2013; Panchaud et al., 2013a); FLCN-FNIP (Lst4-Lst7 in yeast), a GAP for RagC/RagD/Gtr2 (Péli-Gulli et al., 2015; Petit et al., 2013; Tsun et al., 2013); GATOR2, an inhibitor of GATOR1 (Bar-Peled et al., 2013”
From Signal integration in the (m)TORC1 growth pathway (2018) · cites this paper as Bar-Peled et al., 2013
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Citations
Cites
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 · cited 1×
“addition of 50 μl of sample buffer and boiling for 5 minutes as described (1), resolved by 8%–16% SDS-PAGE, and analyzed by immunoblotting.”
Self-citationComprehensive genomic characterization defines human glioblastoma genes and core pathways
The Cancer Genome Atlas Research Network (2008) · Nature · doi:10.1038/nature07385 · Cited by 7,735
Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex
Sarbassov, D. D., Guertin, D. A., Ali, S. M., & Sabatini, D. M. (2005) · Science · doi:10.1126/science.1106148 · Cited by 6,216
Self-citationKim, D., Sarbassov, D. D., Ali, S. M., King, J. E., Latek, R. R., Erdjument‐Bromage, H., Tempst, P., & Sabatini, D. M. (2002) · Cell · doi:10.1016/s0092-8674(02)00808-5 · Cited by 3,051
Self-citationThe Rag GTPases Bind Raptor and Mediate Amino Acid Signaling to mTORC1
Sancak, Y., Peterson, T. R., Shaul, Y. D., Lindquist, R. A., Thoreen, C. C., Bar-Peled, L., & Sabatini, D. M. (2008) · Science · doi:10.1126/science.1157535 · Cited by 2,773 · cited 1×
“shRNA-encoding plasmids were co-transfected with the ∆VPR envelope and CMV VSVG packaging plasmids into actively growing HEK-293T cells using Xtremegene 9 transfection reagent as previously described (4).”
Self-citationMolecular 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 · cited 2×
“Mass spectrometric analyses HEK-293T cells stably expressing FLAG-tagged Metap2, RagB, Mios, DEPDC5, WDR24, or Nprl2 were chemically crosslinked with DSP prior to cell lysis with Triton lysis buffer as described in (2).”
Sancak, Y., Bar-Peled, L., Zoncu, R., Markhard, A. L., Nada, S., & Sabatini, D. M. (2010) · Cell · doi:10.1016/j.cell.2010.02.024 · Cited by 2,464
Self-citationAbsolute quantification of somatic DNA alterations in human cancer
Carter, S. L., Cibulskis, K., Helman, E., McKenna, A., Shen, H., Zack, T. I., Laird, P. W., Onofrio, R. C., Winckler, W., Weir, B. A., et al. (2012) · Nature Biotechnology · doi:10.1038/nbt.2203 · Cited by 2,031
Self-citationZoncu, R., Bar-Peled, L., Efeyan, A., Wang, S., Sancak, Y., & Sabatini, D. M. (2011) · Science · doi:10.1126/science.1207056 · Cited by 1,673 · cited 2×
“The resulting digests were analyzed by mass spectrometry as described (3).”
Self-citationRegulation of TORC1 by Rag GTPases in nutrient response
Kim, E., Goraksha-Hicks, P., Li, L., Neufeld, T. P., & Guan, K.-L. (2008) · Nature Cell Biology · doi:10.1038/ncb1753 · Cited by 1,349 · cited 1×
“Nucleotide Exchange Assays These assays were essentially performed as described in (5).”
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Dynamics of mTORC1 activation in response to amino acids
Manifava, M., Smith, M. D., Rotondo, S., Walker, S. A., Niewczas, I. S., Zoncu, R., Clark, J. P., & Ktistakis, N. T. (2016) · eLife · doi:10.7554/elife.19960 · Cited by 123
Lysosomes: Signaling Hubs for Metabolic Sensing and Longevity
Savini, M., Zhao, Q., & Wang, M. C. (2019) · Trends in Cell Biology · doi:10.1016/j.tcb.2019.08.008 · Cited by 116
Gururajan, M., Josson, S., Chu, G., Lu, C.-L., Lu, Y.-T., Haga, C., Zhau, H., Liu, C.-Y., Lichterman, J., Duan, P., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-1784 · Cited by 105
“NPRL2 activates AKT pathway (39, 40) and RBL2 activates the E2F pathway (41).”
BackgroundAmino acid management in cancer
Tsun, Z.-Y., & Possemato, R. (2015) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2015.08.002 · Cited by 120
Real-world utility of whole exome sequencing with targeted gene analysis for focal epilepsy.
Perucca, P., Scheffer, I., Harvey, A., James, P., Lunke, S., Thorne, N., Gaff, C., Regan, B. M., Damiano, J., Hildebrand, M. S., et al. (2017) · Epilepsy Research · doi:10.1016/j.eplepsyres.2017.02.001 · Cited by 103
New developments in AMPK and mTORC1 cross-talk
Smiles, W. J., Ovens, A. J., Kemp, B. E., Galić, S., Petersen, J., & Oakhill, J. S. (2024) · Essays in Biochemistry · doi:10.1042/ebc20240007 · Cited by 124
“DHAP availability is transduced to mTORC1 via the GATOR2-GATOR1 apparatus that is responsible for GTP turnover of RagA/B. GATOR1 is recruited to the lysosome by another protein complex called KICSTOR and inhibits mTORC1 through its GAP activity towards RagA/B [56,57].”
Cabrera, M., Nordmann, M., Perz, A., Schmedt, D., Gerondopoulos, A., Barr, F., Piehler, J., Engelbrecht-Vandré, S., & Ungermann, C. (2014) · Journal of Cell Science · doi:10.1242/jcs.140921 · Cited by 102
Shen, K., Choe, A., & Sabatini, D. M. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.09.026 · Cited by 101
“…including Ragulator, which localizes them to the lysosomal surface and modulates their nucleotide loading (Sancak et al., 2010), and the GATOR1 (Bar-Peled et al., 2013; Panchaud et al., 2013) and FLCN-FNIP2 (Petit et al., 2013; Tsun et al., 2013), which are GAPs for RagA/B and RagC/D,…”
InfluentialSelf-citationThe Structure Inventory of the Nuclear Pore Complex
Schwartz, T. (2016) · Journal of Molecular Biology · doi:10.1016/j.jmb.2016.03.015 · Cited by 110
“Sec13 and Seh1 are furthermore found as a member of the SEACAT/GATOR2 amino-acid sensing arm of the TOR/mTOR pathway presumably anchored via an insertion-blade as well [59,60].”
BackgroundFamilial cortical dysplasia type IIA caused by a germline mutation in DEPDC5
Scerri, T., Riseley, J. R., Gillies, G., Pope, K., Burgess, R., Mandelstam, S., Dibbens, L., Chow, C., Maixner, W., Harvey, A., et al. (2015) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.191 · Cited by 101
“shRNA-mediated downregulation of DEPDC5 in vitro was associated with constitutive localization of mTOR to the lysosomal surface and dysregulated activity.(7) Consistent with these in vitro studies, we demonstrate for the first time mTOR dysregulation in brain tissue of individuals with DEPDC5 mutations.”
BackgroundResultInfluentialTracing the Archaeal Origins of Eukaryotic Membrane-Trafficking System Building Blocks
Klinger, C. M., Spang, A., Dacks, J. B., & Ettema, T. J. G. (2016) · Molecular Biology and Evolution · doi:10.1093/molbev/msw034 · Cited by 98
“As in other prokaryotes, the various lokiarchaeal MglB homologues could serve as GAPs in this organism (supplementary text S5, Supplementary Material online).”
BackgroundInfluentialAtomic structure of the Y complex of the nuclear pore
Kelley, K., Knockenhauer, K. E., Kabachinski, G., & Schwartz, T. (2015) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2998 · Cited by 99
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 121
“On the other hand, mutations in components of the nutrient sensing machinery upstream of mTORC1, such as GATOR1 in glioblastoma (Bar-Peled et al., 2013), RagC in follicular lymphoma (Okosun et al.”
BackgroundMolecular basis and current strategies of therapeutic arginine depletion for cancer
Fultang, L., Vardon, A., Santo, C. D., & Mussai, F. (2016) · International Journal of Cancer · doi:10.1002/ijc.30051 · Cited by 98
“The GAP complexes (GATOR, of which there are two isoforms: GATOR1 and GATOR2) controls the GTPase hydrolytic activity of Rag downstream of amino sufficiency.(22) GATOR1, which regulates RagA and RagB is itself negatively regulated by GATOR2.”
BackgroundThe role of nicotinic acetylcholine receptors in autosomal dominant nocturnal frontal lobe epilepsy
Becchetti, A., Aracri, P., Meneghini, S., Brusco, S., & Amadeo, A. (2015) · Frontiers in Physiology · doi:10.3389/fphys.2015.00022 · Cited by 107
“The DEPDC protein participates in a molecular complex implicated in repressing the activity of mTORC1 (Target Of Rapamycin Complex 1; Bar-Peled et al., 2013).”
BackgroundLeucine induced dephosphorylation of Sestrin2 promotes mTORC1 activation
Kimball, S. R., Gordon, B. S., Moyer, J. E., Dennis, M. D., & Jefferson, L. S. (2016) · Cellular Signalling · doi:10.1016/j.cellsig.2016.03.008 · Cited by 97
“Epistasis studies place GATOR2 upstream of GATOR1 in the amino acid signaling pathway to mTORC1, leading to the proposal that amino acids signal to mTORC1 by promoting GATOR2-mediated repression of GATOR1 GAP activity toward RagA/B [14].”
BackgroundInfluentialSeizing the moment: Zebrafish epilepsy models
Gaweł, K., Langlois, M., Martins, T., van der Ent, W., Tiraboschi, E., Jacmin, M., Crawford, A. D., & Esguerra, C. V. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.06.010 · Cited by 114
“DEPDC5 encodes a protein which is a member of GATOR1 (Gap Activity Towards Rags) complex, being a negative regulator of mTORC1 (mechanistic target of rapamycin complex 1) (Bar-Peled et al., 2013; Marsan and Baulac, 2018).”
MAP4K3 mediates amino acid-dependent regulation of autophagy via phosphorylation of TFEB
Hsu, C. L., Lee, E. X., Gordon, K. L., Paz, E. A., Shen, W.-C., Ohnishi, K., Meisenhelder, J., Hunter, T. R., & Spada, A. R. L. (2018) · Nature Communications · doi:10.1038/s41467-018-03340-7 · Cited by 110
Nutrient-sensing mTORC1 and AMPK pathways in chronic kidney diseases
Huynh, C. Q., Ryu, J., Lee, J., Inoki, A., & Inoki, K. (2022) · Nature Reviews Nephrology · doi:10.1038/s41581-022-00648-y · Cited by 109
Lawrence, R. E., Cho, K. F., Rappold, R., Thrun, A., Tofaute, M. J., Kim, D. J., Moldavski, O., Hurley, J. H., & Zoncu, R. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0148-6 · Cited by 107
mTOR and the health benefits of exercise
Watson, K., & Baar, K. (2014) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2014.08.013 · Cited by 109
Ribosomal Protein S6: A Potential Therapeutic Target against Cancer?
Yi, Y. W., You, K. S., Park, J., Lee, S., & Seong, Y. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms23010048 · Cited by 100
“SHE1 (nucleoporin SHE1) 3 A component of GAP activity towards RAGs 2 (GATOR2) complex that indirectly activates mTORC1 through inhibiting the GATOR1 complex [194] 3 SHE1-KD by RNAi inhibits p-RPS6 (S235/236) in MIA PaCa-2 cells [79]”
BackgroundEukaryotic translation initiation factors as promising targets in cancer therapy
Hao, P., Yu, J., Ward, R. J., Liu, Y., Qiao, H., An, S., & Xu, T. (2020) · Cell Communication and Signaling · doi:10.1186/s12964-020-00607-9 · Cited by 127
Depdc5 knockout rat: A novel model of mTORopathy.
Marsan, E., Ishida, S., Schramm, A. E., Weckhuysen, S., Muraca, G., Lecas, S., Liang, N., Treins, C., Pende, M., Roussel, D., et al. (2016) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.02.010 · Cited by 95
Yang, Y.-S., Kato, M., Wu, X., Litsios, A., Sutter, B. M., Wang, Y., Hsu, C.-H., Wood, N. E., Lemoff, A. S., Mirzaei, H., et al. (2019) · Cell · doi:10.1016/j.cell.2019.02.043 · Cited by 99
“This complex has emerged as the more evolutionary conserved negative regulator of TORC1 that functions in response to amino acid insufficiency (Bar-Peled et al., 2013; Panchaud et al., 2013).”
Lysosomes and Cancer Progression: A Malignant Liaison
Machado, E., Annunziata, I., van de Vlekkert, D., Grosveld, G. C., & d’Azzo, A. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.642494 · Cited by 102
Yuskaitis, C. J., Jones, B. M., Wolfson, R. L., Super, C. E., Dhamne, S. C., Rotenberg, A., Sabatini, D. M., Şahin, M., & Poduri, A. (2017) · Neurobiology of Disease · doi:10.1016/j.nbd.2017.12.010 · Cited by 116
Self-citationAmino acids and autophagy: cross-talk and co-operation to control cellular homeostasis
Carroll, B., Korolchuk, V. I., & Sarkar, S. (2014) · Amino Acids · doi:10.1007/s00726-014-1775-2 · Cited by 99
“The V-ATPase interacts with the Ragulator and positively regulates mTORC1 activity in response to amino acids in an ATP-dependent manner (Zoncu et al. 2011) MAP4K3 MAP4K3 participates in amino acid-dependent activation of mTORC1; mechanism unknown (Findlay et al. 2007) IPMK IPMK has low binding affinity to the mTOR–Ra…”
BackgroundInfluentialHao, F., Kondo, K., Itoh, T., Ikari, S., Nada, S., Okada, M., & Noda, T. (2018) · Journal of Cell Science · doi:10.1242/jcs.208017 · Cited by 91
Regulation of CD8+ T memory and exhaustion by the mTOR signals
Chen, Y., Xu, Z., Sun, H., Ouyang, X., Han, Y., Yu, H., Wu, N., Xie, Y., & Su, B. (2023) · Cellular and Molecular Immunology · doi:10.1038/s41423-023-01064-3 · Cited by 101
mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics
Zhang, H., Xiao, X., Pan, Z., & Dokudovskaya, S. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02493-4 · Cited by 94
Nutrients: Signal 4 in T cell immunity
Raynor, J. L., & Chi, H. (2024) · The Journal of Experimental Medicine · doi:10.1084/jem.20221839 · Cited by 99
Ferguson, S. M. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2018.04.005 · Cited by 107
“The Nprl2, Nprl3 and DEPDC5 proteins form the GATOR1 complex which has GTPase activating protein (GAP) activity towards the lysosomelocalized RagA/B proteins and which thereby suppresses mTORC1 activity when amino acid levels are low (106).”
BackgroundHybrid Structure of the RagA/C-Ragulator mTORC1 Activation Complex
Su, M.-Y., Morris, K. L., Kim, D. J., Fu, Y., Lawrence, R. E., Stjepanović, G., Zoncu, R., & Hurley, J. H. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.10.016 · Cited by 96
“Conversely, in high nutrients the RagC/D-specific GAP, Folliculin (FLCN)-FNIP, promotes switching of the Rag heterodimer to themTORC1-binding configuration (Péli-Gulli et al., 2015; Petit et al., 2013; Tsun et al., 2013).”
BackgroundInfluentialSestrin regulation of TORC1: Is Sestrin a leucine sensor?
Lee, J. H., Cho, U., & Karin, M. (2016) · Science Signaling · doi:10.1126/scisignal.aaf2885 · Cited by 84
mTORC1, the maestro of cell metabolism and growthPreprint
He, L., Cho, S., & Blenis, J. (2024) · Genes & Development · doi:10.1101/gad.352084.124 · Cited by 88
“In summary, the phosphorylation and subcellular localization of MiT-TFE factors show a distinct insensitivity to growth factor-induced activation of RagA/B, setting them apart from other mTORC1 substrates like S6K and 4E-BP1.”
InfluentialRegulation of metabolic health by essential dietary amino acids
Green, C. L., & Lamming, D. W. (2018) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2018.07.004 · Cited by 91
Leucyl-tRNA Synthetase Activates Vps34 in Amino Acid-Sensing mTORC1 Signaling
Yoon, M., Son, K., Arauz, E. J., Han, J. M., Kim, S., & Chen, J. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.07.008 · Cited by 98
“The Ragulator complex and the GATOR1 complex act as GEF (guanine nucleotide exchange factor) and GAP (GTPase activating protein) for RagA/B, respectively (Bar-Peled et al., 2013; Bar-Peled et al., 2012).”
BackgroundFolliculin: A Regulator of Transcription Through AMPK and mTOR Signaling Pathways
Ramírez-Reyes, J. M. J., Cuesta, R., & Pause, A. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.667311 · Cited by 98
The role of genetic testing in epilepsy diagnosis and management
Weber, Y., Biskup, S., Helbig, K., von Spiczak, S., & Lerche, H. (2017) · Expert Review of Molecular Diagnostics · doi:10.1080/14737159.2017.1335598 · Cited by 87
“DEPDC5 is part of the GATOR1 complex which acts as an inhibitor of the mTORC1 complex [65,66].”
BackgroundKim, J. H., Lee, C., Lee, M., Wang, H., Kim, K., Park, S. J., Yoon, I., Jang, J., Zhao, H., Kim, H. K., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00785-0 · Cited by 88
Sterol transporters at membrane contact sites regulate TORC1 and TORC2 signaling
Murley, A., Yamada, J., Niles, B. J., Toulmay, A., Prinz, W., Powers, T., & Nunnari, J. (2017) · Journal of Cell Biology · doi:10.1083/jcb.201610032 · Cited by 86
“…complex; and the Gtr1 GTPase-activating protein (GAP) Iml1, a subunit of the upstream negative TORC1 regulator SEAC subcomblex inhibiting TORC1 signaling (SEA CIT) complex that, together with Npr2/3, is equivalent to the mammalian GAT OR1 complex (Bar-Peled et al., 2013; Panchaud et al., 2013).”
BackgroundIffland, P. H., Carson, V., Bordey, A., & Crino, P. B. (2019) · Epilepsia · doi:10.1111/epi.16370 · Cited by 84
mTOR signaling pathway genes in focal epilepsies
Baulac, S. (2016) · Progress in Brain Research · doi:10.1016/bs.pbr.2016.04.013 · Cited by 84
A network of human functional gene interactions from knockout fitness screens in cancer cells
Kim, E., Dede, M., Lenoir, W. F., Wang, G., Srinivasan, S., Colic, M., & Hart, T. (2019) · Life Science Alliance · doi:10.26508/lsa.201800278 · Cited by 85
“The GATOR-1 complex is a nonessential suppressor of essential Rag GTPase activity (Bar-Peled et al, 2013) and is, therefore, absent from our network, but essential suppression of GATOR-1 by GATOR-2 (Bar-Peled et al, 2013; Wei et al, 2014) is re fl ected by the strong linkage of the GATOR-2 complex…”
Jin, G., Lee, S.-W., Zhang, X., Cai, Z., Gao, Y., Chou, P., Rezaeian, A. H., Han, F., Wang, C., Yao, J.-C., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.05.010 · Cited by 89
“For the analysis of interactions between RagA, GATOR1, Ragulator, and Skp2, the cells were treated with crosslinker DSP before lysis as previously described (Bar-Peled et al., 2012, 2013).”
InfluentialMolecular Architecture and Function of the SEA Complex, a Modulator of the TORC1 Pathway
Algret, R., Fernández-Martı́nez, J., Shi, Y., Kim, S. J., Pellarin, R., Cimermančič, P., Cochet, E., Šali, A., Chait, B. T., Rout, M. P., et al. (2014) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m114.039388 · Cited by 87
“SEA4, W T (#17) SEA4, SEA3Δ (#18) SEA4, SEA3Δ (#19) SEA4, NPR3Δ (#20) SEA4(1-498) (#21) SEA4(1-589) (#SF2) SEA4(1-930) (#22) SEA1, SEA4Δ (#4) SEA1 G (#2) SEA1(1-537) (#5) - - - - - + + + + + + + + + + + + + + + + SE C1 3 + - + - - + - - - - + 537 SE A 2 + - + + - + - - - - + + + - -+ - - 615 + + + + + + + + + + 1NPR2,…”
BackgroundInfluentialNeocortical development and epilepsy: insights from focal cortical dysplasia and brain tumours
Blümcke, I., Budday, S., Poduri, A., Lal, D., Kobow, K., & Baulac, S. (2021) · The Lancet Neurology · doi:10.1016/s1474-4422(21)00265-9 · Cited by 100
Conserved regulators of Rag GTPases orchestrate amino acid-dependent TORC1 signaling
Powis, K., & VIRGILIO, C. D. (2016) · Cell Discovery · doi:10.1038/celldisc.2015.49 · Cited by 80
Huang, N., Winans, T., Wyman, B., Oaks, Z., Faludi, T., Choudhary, G., Lai, Z., Lewis, J., Beckford, M., Duarte, M., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-46441-2 · Cited by 87
“As documented in this study, mTOR is traf fi cked by Rab4A to the lysosome, where it gets activated within the cell 109,110 .”
BackgroundE3 ligase RNF167 and deubiquitinase STAMBPL1 modulate mTOR and cancer progression
Wang, D., Xu, C., Yang, W., Chen, J., Ou, Y., Guan, Y., Guan, J., & Liu, Y. (2022) · Molecular Cell · doi:10.1016/j.molcel.2022.01.002 · Cited by 83
Lee, M., Kim, J. H., Yoon, I., Lee, C., Fallahi‐Sichani, M., Kang, J. S., Kang, J., Guo, M., Lee, K. Y., Han, G., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1801287115 · Cited by 90
“Namely, during leucine signaling, LRS initiates the Rag GTPase cycle via RagD whereas Sestrin2 terminates the Rag GTPase cycle by controlling RagA–RagB GAP activity of GATOR1 via GATOR2 inhibition.”
BackgroundInfluentialGenomic landscape of pancreatic neuroendocrine tumours: the International Cancer Genome Consortium
Mafficini, A., & Scarpa, A. (2018) · Journal of Endocrinology · doi:10.1530/joe-17-0560 · Cited by 98
“The fourth relevant observation regards the analysis of somatically altered driver genes that confirmed a heavy involvement of the chromatin remodeling and PI3K/mTOR pathway in PanNETs development, with MEN1 (36 cases) as the top driver gene, DAXX (22 cases) and ATRX (10 mutated, one rearranged case) mutually exclusiv…”
BackgroundInfluentialmTORC1 Overactivation as a Key Aging Factor in the Progression to Type 2 Diabetes Mellitus
Guillén, C., & Benito, M. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00621 · Cited by 91
“RagA/B-GDP through GAP activity of GATOR1 (20) and the guanine exchange factor activity (GEF) of the complex called “Ragulator” (21).”
BackgroundLi, M., Yu, J., Tilgner, K., Ong, S. H., Koike-Yusa, H., & Yusa, K. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.06.027 · Cited by 96
“The Gator1 complex also negatively regulates mTORC1 activity through its GAP activity toward RagA in response to amino acid sensing (Bar-Peled et al., 2013) (Figure 4A).”
GATOR1 complex: the common genetic actor in focal epilepsies
Baldassari, S., Licchetta, L., Tinuper, P., Bisulli, F., & Pippucci, T. (2016) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2016-103883 · Cited by 80
Structure of the nutrient-sensing hub GATOR2
Valenstein, M. L., Rogala, K. B., Lalgudi, P. V., Brignole, E. J., Gu, X., Saxton, R. A., Chantranupong, L., Kolibius, J., Quast, J.-P., & Sabatini, D. M. (2022) · Nature · doi:10.1038/s41586-022-04939-z · Cited by 94
Self-citationRegulation of mTORC1 by Upstream Stimuli
Melick, C. H., & Jewell, J. L. (2020) · Genes · doi:10.3390/genes11090989 · Cited by 104
“The Ragulator and solute carrier family 38 member 9 (SLC38A9) have been suggested to act as GEFs for RagA/B [100,102].”
BackgroundInfluentialLiu, Z., Yan, M., Liang, Y., Liu, M., Zhang, K., Shao, D., Jiang, R., Li, L., Wang, C., Nussenzveig, D. R., et al. (2019) · Neuron · doi:10.1016/j.neuron.2019.02.018 · Cited by 86
Norambuena, A., Wallrabe, H., McMahon, L., Silva, A., Swanson, E., Khan, S. S., Baerthlein, D., Kodis, E., Oddo, S., Mandell, J. W., et al. (2017) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.08.015 · Cited by 79
“7) Plasmid to knockdownNprl3was from the RNAi Consortium of the Broad Institute (TRCN0000175195).”
InfluentialQi, B., Kniazeva, M., & Han, M. (2017) · eLife · doi:10.7554/elife.26243 · Cited by 94
“NPRL-3 is a negative regulator of TORC1 in both worms and mammalian cells (Bar-Peled et al., 2013; Zhu et al., 2013).”
BackgroundDEPTOR at the Nexus of Cancer, Metabolism, and Immunity
Caron, A., Briscoe, D. M., Richard, D., & Laplante, M. (2018) · Physiological Reviews · doi:10.1152/physrev.00064.2017 · Cited by 87
Beyond controlling cell size: functional analyses of S6K in tumorigenesis
Wu, X., Xie, W., Xie, W., Wei, W., & Guo, J. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-05081-4 · Cited by 96
“Thus, signals regulating these components will also modulate mTORC1 kinase activity and subsequently S6K phosphorylation [8, 99, 100].”
BackgroundTinuper, P., & Bisulli, F. (2017) · Seizure · doi:10.1016/j.seizure.2016.11.023 · Cited by 77
Epileptic spasms are a feature of DEPDC5 mTORopathy
Carvill, G. L., Crompton, D. E., Regan, B. M., McMahon, J. M., Saykally, J., Zemel, M., Schneider, A. L., Dibbens, L., Howell, K. B., Mandelstam, S., et al. (2015) · Neurology Genetics · doi:10.1212/nxg.0000000000000016 · Cited by 76
mTOR pathway: Insights into an established pathway for brain mosaicism in epilepsy
Gerasimenko, A., Baldassari, S., & Baulac, S. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106144 · Cited by 85
mTORC1 senses stresses: Coupling stress to proteostasis
Su, K., & Dai, C. (2017) · BioEssays · doi:10.1002/bies.201600268 · Cited by 82
“Subsequently, the GTP-loaded RagA/B that is heterodimerized with the GDP-loaded RagC/D recruit inactive mTORC1 from the cytosol to the lysosomal surface, where it becomes activated by RheB [49,50].”
BackgroundInfluentialStructural basis for the assembly of the Ragulator-Rag GTPase complex
Yonehara, R., Nada, S., Nakai, T., Nakai, M., Kitamura, A., Ogawa, A., Nakatsumi, H., Nakayama, K. I., Li, S., Standley, D. M., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01762-3 · Cited by 75
Proteome activity landscapes of tumor cell lines determine drug responses
Frejno, M., Meng, C., Ruprecht, B., Oellerich, T., Scheich, S., Kleigrewe, K., Drecoll, E., Samaras, P., Hogrebe, A., Helm, D., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17336-9 · Cited by 85
Amino Acids Regulate mTORC1 by an Obligate Two-step Mechanism
Dyachok, J., Earnest, S. A., Iturraran, E. N., Cobb, M. H., & Ross, E. M. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.732511 · Cited by 92
“Amino acids promote the GTP-loaded state of the RagA/B subunit and GDP-loaded state of the RagC/D subunits and thus drive Rag heterodimer binding to the Raptor subunit of mTORC1 with consequent mTORC1 recruitment to lysosomes (12, 18).”
BackgroundBoeckstaens, M., Llinares, E., Vooren, P. V., & Marini, A. M. (2014) · Nature Communications · doi:10.1038/ncomms4101 · Cited by 76
The Architecture of the Rag GTPase Signaling Network
Nicastro, R., Sardu, A., Panchaud, N., & VIRGILIO, C. D. (2017) · Biomolecules · doi:10.3390/biom7030048 · Cited by 76
“SEACIT and SEACAT have functionally and structurally related orthologs in mammals named GATOR1 (GAP activity towards Rags; containing DEPDC5, NPRL2, and NPRL3) and GATOR2 (containing Seh1L, Sec13, Wdr24, Wdr59, and Mios), respectively [89,90].”
BackgroundSerine and one-carbon metabolism, a bridge that links mTOR signaling and DNA methylation in cancer
Zeng, J., Wu, W. K. K., Wang, H., & Li, X. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.104352 · Cited by 96
mTOR in programmed cell death and its therapeutic implications
Xie, Y., Lei, X., Zhao, G., Guo, R., & Cui, N. (2023) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2023.06.002 · Cited by 83
Exaptive Evolution of Target of Rapamycin Signaling in Multicellular Eukaryotes
Brunkard, J. O. (2020) · Developmental Cell · doi:10.1016/j.devcel.2020.06.022 · Cited by 89
“GATOR2 then represses GATOR1, which otherwise inactivates TOR (Bar-Peled et al., 2013).”
BackgroundExiting the ER: what we know and what we don't.
Venditti, R., Wilson, C., & Matteis, M. D. D. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2013.08.005 · Cited by 72
Dynamic relocation of the TORC1–Gtr1/2–Ego1/2/3 complex is regulated by Gtr1 and Gtr2
Kira, S., Kumano, Y., Ukai, H., Takeda, E., Matsuura, A., & Noda, T. (2015) · Molecular Biology of the Cell · doi:10.1091/mbc.e15-07-0470 · Cited by 77
“Gtr1 is kept as a GTP-bound form in the mutant of NPR2, a subunit of the SEACIT complex, which has GTPase activation protein (GAP) activity toward Gtr1, leading to persistent activation of TORC1 (Bar-Peled et al., 2013; Panchaud et al., 2013a,b; Kira et al., 2014).”
BackgroundFunctional unknomics: Systematic screening of conserved genes of unknown function
Rocha, J. J., Jayaram, S. A., Stevens, T. J., Muschalik, N., Shah, R. D., Emran, S., Robles, C., Freeman, M., & Munro, S. (2023) · PLOS Biology · doi:10.1371/journal.pbio.3002222 · Cited by 70
Hino, H., Iriyama, N., Kokuba, H., Kazama, H., Moriya, S., Takano, N., Hiramoto, M., Aizawa, S., & Miyazawa, K. (2020) · Cancer Science · doi:10.1111/cas.14419 · Cited by 78
Mechanisms of Autophagy in Metabolic Stress Response
Gross, A. S., & Graef, M. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.09.005 · Cited by 77
Meng, J., & Ferguson, S. M. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201712177 · Cited by 75
“GAT OR1 is a heterotrimeric protein complex made up of NPRL2, NPRL3, and DEP DC5, whose GAP activity toward RagA/B is tightly controlled by amino acid availability via signals received from upstream amino acid sensors (Bar-Peled et al., 2013; Panchaud et al., 2013; Chantranupong et al., 2014, 2016; Parmigiani et al.,…”
BackgroundDrug discovery targeting the mTOR pathway
Martelli, A. M., Buontempo, F., & McCubrey, J. A. (2018) · Clinical Science · doi:10.1042/cs20171158 · Cited by 77
SEA you later alli-GATOR – a dynamic regulator of the TORC1 stress response pathway
Dokudovskaya, S., & Rout, M. P. (2015) · Journal of Cell Science · doi:10.1242/jcs.168922 · Cited by 74
“…GTPases must haveGAPs (Han et al., 2012; Tsun et al., 2013), GEFs (Bar-Peled et al., 2012;Binda et al., 2009;Bonfils et al., 2012;Petit et al., 2013) and GDIs (Kim et al., 2012; Peng et al., 2014) – and this is where the SEA (GATOR) complex comes in (Bar-Peled et al., 2013; Panchaud et al., 2013a).”
BackgroundResultInfluentialLevin‐Salomon, V., Bialik, S., & Kimchi, A. (2013) · APOPTOSIS · doi:10.1007/s10495-013-0918-3 · Cited by 76
“Interestingly, DAPK has also been linked to the regulatory stage of DAPK induction through its interaction with TSC2, the GAP for the mTOR regulator Rheb.”
BackgroundInfluentialLamming, D. W., Cummings, N. E., Rastelli, A. L., Gao, F., Cava, E., Bertozzi, B., Spelta, F., Pili, R., & Fontana, L. (2015) · Oncotarget · doi:10.18632/oncotarget.5180 · Cited by 69
The tRNA-GCN2-FBXO22-axis-mediated mTOR ubiquitination senses amino acid insufficiency
Ge, M.-K., Zhang, C., Zhang, N., He, P., Cai, H., Li, S., Wu, S., Chu, X., Zhang, Y., Ma, H., et al. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.10.016 · Cited by 73
Xu, D., Shimkus, K. L., Lacko, H. A., Kutzler, L., Jefferson, L. S., & Kimball, S. R. (2019) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00522.2018 · Cited by 77
“, Sestrin2, that in turn acts to relieve repression of a complex referred to as GAP activity toward Rags 2 (GATOR2), which consists of the proteins meiosis regulator for oocyte development (Mios), WD repeat-domain-containing proteins 24 and 59 (WDR24 and WDR59, respectively), Sec13, and Sec13-like protein (Seh1l) (4).”
BackgroundMAX Functions as a Tumor Suppressor and Rewires Metabolism in Small Cell Lung Cancer
Augert, A., Mathsyaraja, H., Ibrahim, A. H., Freie, B. W., Geuenich, M., Cheng, P.-F., Alibeckoff, S. P., Wu, N., Hiatt, J. B., Basom, R., et al. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.04.016 · Cited by 80
“Additional negative regulators of mTORC1 signaling were also uncovered including Sesn3, Ddit4 (Brugarolas et al., 2004; Parmigiani et al., 2014) and genes encoding two subunits of GATOR1: Depdc5 and Nprl3 (Bar-Peled et al., 2013; Panchaud et al., 2013).”
BackgroundLysosomal Regulation of mTORC1 by Amino Acids in Mammalian Cells
Yao, Y., Jones, E. Y., & Inoki, K. (2017) · Biomolecules · doi:10.3390/biom7030051 · Cited by 69
“Previous studies have indicated that GATOR1 inhibits RagA/B through its GAP activity while GATOR2 functions as a suppressor of GATOR1 through unknown mechanisms [63] (Figure 1).”
BackgroundResultInfluentialKira, S., Tabata, K., Shirahama‐Noda, K., Nozoe, A., Yoshimori, T., & Noda, T. (2014) · Autophagy · doi:10.4161/auto.29397 · Cited by 77
“28 In mammals, a protein complex called GATOR1, which contains NPRL2 and NPRL3, exert GAP activity toward RRAGA/B.29 Therefore, our results are consistent with the idea that the Npr2-Npr3 complex is required for GAP activity toward Gtr1.”
ResultmTOR Signaling in Autophagy Regulation in the Kidney
Inoki, K. (2013) · Seminars in Nephrology · doi:10.1016/j.semnephrol.2013.11.002 · Cited by 71
mTOR controls ChREBP transcriptional activity and pancreatic β cell survival under diabetic stress
Chau, G. C., Im, D. U., Kang, T. M., Bae, J. M., Kim, W., Pyo, S., Moon, E.-Y., & Um, S. H. (2017) · Journal of Cell Biology · doi:10.1083/jcb.201701085 · Cited by 67
“…activity of Ragulator, a complex encoded by the MAP KSP1, ROB LD3, and c11orf59 genes (Sancak et al., 2010), and inhibits the GTPase activating protein activity of GTPase activating protein activity toward Rags 1 (Bar-Peled et al., 2013), leading to the formation of heterodimeric complex RagA.”
BackgroundSpatial and functional separation of mTORC1 signalling in response to different amino acid sources
Fernandes, S., Angelidaki, D.-D., Nüchel, J., Pan, J., Gollwitzer, P., Elkis, Y., Artoni, F., Wilhelm, S., Kovacevic-Sarmiento, M., & Demetriades, C. (2024) · Nature Cell Biology · doi:10.1038/s41556-024-01523-7 · Cited by 69
“However, in line with previous work on the role of the Rags in glucose signalling to mTORC1 on lysosomes (for example, fig.”
InfluentialStructure of the C9orf72 ARF GAP complex that is haploinsufficient in ALS and FTD
Su, M.-Y., Fromm, S. A., Zoncu, R., & Hurley, J. H. (2020) · Nature · doi:10.1038/s41586-020-2633-x · Cited by 83
Metabolic Networks Influencing Skeletal Muscle Fiber Composition
Bourdeau‐Julien, I., Sephton, C. F., & Dutchak, P. A. (2018) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2018.00125 · Cited by 83
“Low concentrations of intracellular amino acids cause GATOR1 dissociation from its negative regulatory complex called GATOR2, permitting GATOR1 to catalyze GTPRag hydrolysis to GDP-Rag and impair mTORC1 activity (Figure 1A) (Bar-Peled et al., 2013).”
BackgroundPrecision medicine in genetic epilepsies: break of dawn?
Reif, P. S., Tsai, M., Helbig, I., Rosenow, F., & Klein, K. M. (2016) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2017.1253476 · Cited by 77
Regulation of metabolic health and aging by nutrient-sensitive signaling pathways
Richardson, N. E., & Lamming, D. W. (2016) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2016.11.014 · Cited by 73
“Amino acid binding by Sestrin2, particularly with respect to leucine, is reported to disrupt the interaction of Sestrin2 and GATOR2, freeing GATOR2 to inhibit GATOR1 (Saxton et al., 2016; Wolfson et al., 2016).”
BackgroundInfluentialGSK3-mediated raptor phosphorylation supports amino-acid-dependent mTORC1-directed signalling
Stretton, C., Hoffmann, T. M., Munson, M. J., Prescott, A., Taylor, P. M., Ganley, I., & Hundal, H. (2015) · Biochemical Journal · doi:10.1042/bj20150404 · Cited by 67
Zhang, X., Kapoor, D., Jeong, S., Fappi, A., Stitham, J., Shabrish, V., Sergin, I., Yousif, E., Rodríguez-Vélez, A., Yeh, Y., et al. (2024) · Nature Metabolism · doi:10.1038/s42255-024-00984-2 · Cited by 77
“Amino-acid-mediated induction of mTOR occurs through formation of the lysosome-bound Regulator complex and subsequent recruitment of the mTOR complex (mTORC1) to the lysosome surface 57,58 .”
Paez, H. G., Pitzer, C. R., & Alway, S. E. (2023) · Cells · doi:10.3390/cells12020249 · Cited by 71
“The availability of leucine reduces Sestrin2 activity, which relieves inhibition of the protein complex GTPase-activating protein activity toward Rags 2 (GATOR2) [46,47].”
Influential
Metadata
- Authors
- Bar-Peled, L., Chantranupong, L., Cherniack, A. D., Chen, W. W., Ottina, K. A., Grabiner, B. C., Spear, E. D., Carter, S. L., Meyerson, M., & Sabatini, D. M.
- Affiliations
- Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, 9 Cambridge Center, Cambridge, MA 02142, USA.
- Whitehead Institute for Biomedical Research (US)
- Broad Institute (US)
- Johns Hopkins University (US)
- Corresponding author
- Chantranupong, Lynne
- Sabatini, David M.
- ORCID
- Venue
- Science
- Published
- 2013-05-31
- Volume
- 340
- Issue
- 6136
- Pages
- 1100-1106
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3728654
- OpenAlex
- W1519230612
- Cited by
- 1,080
- References
- 32
- Citations by year
- 2026: 40 · 2025: 79 · 2024: 88 · 2023: 89 · 2022: 97 · 2021: 85 · 2020: 91 · 2019: 77 · 2018: 88 · 2017: 83 · 2016: 84 · 2015: 87 · 2014: 69 · 2013: 21
- FWCI
- 38.94
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- PMC
- Funders
- Howard Hughes Medical Institute
- National Cancer Institute (CA103866, R01CA103866, R01CA129105, F31CA180271, U24CA143867, P30CA014051)
- National Institute of Allergy and Infectious Diseases (R37AI047389, AI47389), R01AI047389)
- 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 › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- GATOR1, GATOR2, mTORC1, Rag GTPases, GTPase-activating protein, amino acid signaling, lysosomal translocation, DEPDC5, NPRL2, NPRL3, MIO, Sec13, rapamycin sensitivity, amino acid starvation, cancer
- MeSH terms
- Mechanistic Target of Rapamycin Complex 1, Amino Acids, Carrier Proteins, Humans, Lysosomes, Mutation, Neoplasms, Nuclear Proteins, Proteins, Monomeric GTP-Binding Proteins, GTPase-Activating Proteins, Tumor Suppressor Proteins, RNA, Small Interfering, Cell Line, Tumor, Multiprotein Complexes, HEK293 Cells, TOR Serine-Threonine Kinases
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