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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]
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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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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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New technologies in molecular genetics
Helbig, I. (2014) · Progress in brain research · doi:10.1016/b978-0-444-63326-2.00013-2 · Cited by 6
“…the epilepsy community as this gene may explain up to 10% of all familial focal epilepsies and might hint at an unanticipated connection between nonlesional focal epilepsies and the mTOR pathway, which is implicated in tuberous sclerosis complex and cortical malformations (Bar-Peled et al., 2013).”
BackgroundGenetic landscape and phenotypic correlations of lissencephaly: prenatal and postnatal insights
Huang, R.-B., Fu, F., Zhang, N., Zhou, H., Mei, S., Han, J., Deng, Q., Liu, H.-S., Zhang, Y.-L., Yu, Q.-X., et al. (2026) · Brain Communications · doi:10.1093/braincomms/fcag069 · Cited by 4
“27 The c.318 + 1G > T mutation likely causes GATOR1 dysfunction and abnormal mTORC1 activation, a mechanism confirmed in animal models.”
Lin, Z., He, L., Wang, J., Zhang, H., Yao, S., Guo, J., Zhang, X., Liang, T., & Bai, X. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.108003 · Cited by 3
Human CCR4 deadenylase homolog Angel1 is a non-stop mRNA decay factor
Shaw, T., Dowdle, M. E., Ajaj, Y., Perelis, M., Fulzele, A., Yeo, G. W.-M., Bennett, E. J., & Lykke‐Andersen, J. (2025) · RNA · doi:10.1261/rna.080399.125 · Cited by 5
“In addition to RQC factors, we also found association in our IP-MS/MS analysis of Angel1 with the Gator2 complex which, along with Sestrins and Gator1, is important for sensing amino acid deprivation and signaling through mTORC1 (Bar-Peled et al. 2013; Kowalsky et al. 2020).”
Wang, Y., Ping, Y., Zhou, R., Wang, G., Zhang, Y., Yang, X., Zhao, M., Liu, D., Kulkarni, M., Lamb, H., et al. (2025) · Autophagy · doi:10.1080/15548627.2025.2481014 · Cited by 5
“Cells lacking the SEACIT/GATOR1 components, Npr2 and Npr3, later identified in mammals (NPRL2, NPRL3), have reduced ability to suppress TORC1/MTORC1 activity under low amino acids conditions, especially low leucine [3–5].”
Fischbach, A., Widlund, P. O., Hao, X., & Nyström, T. (2025) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2025.108172 · Cited by 5
“The mammalian ortholog of the SEA complex, known as GATOR, consists of GATOR1 and GATOR2 sub-complexes with inhibitory and stimulating effects on mTOR activity, respectively (13). mTOR primarily controls anabolic processes such as lipid, nucleotide, and protein synthesis.”
Structure and function of the yeast amino acid-sensing SEAC–EGOC supercomplex
Tafur, L., Bonadei, L., Zheng, Y., Gabus, C., & Loewith, R. (2026) · Nature Structural & Molecular Biology · doi:10.1038/s41594-026-01746-2 · Cited by 4
“10,12,16).”
Lin, Q., Tu, X., Li, X., Gou, F., Ding, L.-P., Lu, Z., Feng, J., Ying, Y., & Hu, C.-H. (2024) · Animal Nutrition · doi:10.1016/j.aninu.2024.03.011 · Cited by 4
The RagA GTPase protects young egg chambers in Drosophila
Zhou, Y., Guan, J., Meng, G., Fan, W., Ge, C., Niu, C., Yang, C., Fu, Y., Lu, Y., & Wei, Y. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112631 · Cited by 4
G6PD drives glioma invasion by regulating SQSTM1 protein stability.
Zhang, X., Wang, Z., Zhuo, R., Wang, L.-P., Qin, Y., Han, W., & Peng, X.-Z. (2023) · Gene · doi:10.1016/j.gene.2023.147476 · Cited by 4
Une moisson de nouvelles structures de mTORC1
Nawrotek, A., & Cherfils, J. (2021) · médecine/sciences · doi:10.1051/medsci/2021033 · Cited by 4
Dunlap, K. R., Steiner, J. L., Rossetti, M. L., Kimball, S. R., & Gordon, B. S. (2021) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01064.2020 · Cited by 6
Sun, L., Li, X., Pan, J., Mao, J., Yuan, Y., Wang, D.-X., Sun, W., Krueger, G., & Wang, G. (2019) · Cancer Genomics & Proteomics · doi:10.21873/cgp.20150 · Cited by 4
PQLC2 signals lysosomal cationic amino acid abundance to the C9orf72 complex
Amick, J., Tharkeshwar, A. K., Talaia, G., & Ferguson, S. (2019) · bioRxiv · doi:10.1101/670034 · Cited by 4
“As expected, these cells are unable to efficiently inactivate mTORC1 during amino acid starvation (Fig S2A) (Bar-Peled et al., 2013; Panchaud et al., 2013).”
BackgroundPolleys, E. J., & Bertuch, A. (2015) · G3: Genes, Genomes, Genetics · doi:10.1534/g3.115.018721 · Cited by 4
“This initial study revealed that GATOR2 functions as a positive regulator of mTORC1 by negatively regulating GATOR1, which is an inhibitor of mTORC1 signaling.”
BackgroundMethodInfluentialD’Antona, G. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-801816-3.00011-x · Cited by 3
Virome-wide ubiquitin ligase discovery reveals diverse mechanisms of immune evasion.
Glassman, C., Baek, K., Hou, G.-P., Zeng, Q.-R., Nardone, C., Juergens, K. B., Fujimura, E., O’Leary, C. N., Li, M. Z., Paulo, J. A., et al. (2026) · Science · doi:10.1126/science.aec6299 · Cited by 3
Wang, X.-C., Zhao, Y., Yang, X., Liu, T.-Y., Zhou, W., Niu, S., Jin, M., Chen, Y., Liu, R.-Y., Bao, Y., et al. (2025) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2025.10.039 · Cited by 3
Hu, B., Shang, M.-D., Wang, X., Zhang, X.-G., Dong, M.-H., Cao, Q., Wei, X.-D., Han, Y.-C., Li, F., Yang, Z.-L., et al. (2025) · Cellular Signalling · doi:10.1016/j.cellsig.2025.112110 · Cited by 3
Wang, X.-Z., Wang, H.-Y., Liu, Y., Li, G.-Q., He, D.-Q., Chen, S.-F., Jia, H., Dai, J.-L., & Zhou, X. (2025) · Microorganisms · doi:10.3390/microorganisms13092179 · Cited by 3
“These potential deficiencies could plausibly impair the efficiency of ribosomal protein synthesis downstream of the mTORC1 signaling pathway, potentially reducing the overall efficiency of protein synthesis in the organism, as reported in prior research [28].”
Sestrins in Carcinogenesis—The Firefighters That Sometimes Stoke the Fire
Haidurov, A., & Budanov, A. V. (2025) · Cancers · doi:10.3390/cancers17091578 · Cited by 4
“GATOR1 was initially identified as a tumour suppressor [22].”
Ikeda, T., Hong, S., Yoshida, S., Srivastava, S. P., Kunamneni, A., Yao, Y., Khuperkar, O., Basrur, V., Kuang, H., Kachman, M. T., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116382 · Cited by 1
Solanki, S. A., Taranto, J., Rebernick, R. J., Castillo, C., Ponnusamy, V., Sykes, M. M., Leiser, S. F., Lee, J. H., Schmidt, T. M., & Shah, Y. M. (2025) · Journal of Nutrition · doi:10.1016/j.tjnut.2025.03.031 · Cited by 3
Ahn, E., Kim, S., Park, S., Kim, S., Kim, H., Lee, H., Kim, H., Song, E., Hwang, K.-A., Ahn, T., et al. (2025) · Cancers · doi:10.3390/cancers17071251 · Cited by 3
POLR1D, a shared subunit of RNA polymerase I and III, modulates mTORC1 activity.
Gorjão, N., Borowski, L. S., Szczęsny, R., & Graczyk, D. (2025) · Biochimica et biophysica acta. Molecular cell research · doi:10.1016/j.bbamcr.2025.119957 · Cited by 3
Differential cell survival outcomes in response to diverse amino acid stress
Russier, M., Fiore, A., Bici, A., Groß, A., Tanzer, M. C., Yeroslaviz, A., Mann, M., & Murray, P. J. (2025) · Life Science Alliance · doi:10.26508/lsa.202503324 · Cited by 3
Winczewska-Wiktor, A., Braszka, M., Harada-Laszlo, M., Badura-Stronka, M., Kaczmarek, I., Starczewska, M., Wencel-Warot, A., Steinborn, B., & Jamsheer, A. (2023) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2023.109535 · Cited by 3
Rossetti, C., Alves, B., Peçanha, F. L., Franco, A., Nosé, V., Carneiro, E. M., Lew, J. L., Bernal-Mizrachi, E., & Werneck-de-Castro, J. P. (2023) · bioRxiv · doi:10.1089/thy.2024.0053 · Cited by 3
Modeling genetic mosaicism of the mammalian target of rapamycin pathway in the cerebral cortex
Feliciano, D. M. (2023) · Frontiers in Mammal Science · doi:10.3389/fmamm.2023.1231778 · Cited by 3
mTOR gets greasy: lysosomal sensing of cholesterol
Bar-Peled, L., & Lamming, D. W. (2022) · Cell Research · doi:10.1038/s41422-022-00740-9 · Cited by 3
Self-citationZhou, X., Chen, F.-Y., Ye, X., & Liu, Z. (2022) · Clinical Dysmorphology · doi:10.1097/mcd.0000000000000428 · Cited by 3
Pi, Y.-L., Zhan, Y., Song, J.-T., Jin, X., & Chen, J. (2022) · Journal of Gastrointestinal Oncology · doi:10.21037/jgo-22-115 · Cited by 3
“(6) have revealed that NPRL2 was an inhibitor of mTOR signalling and that cells with NPRL2 mutation were sensitive to rapamycin treatment.”
BackgroundCalvo, I. A., Sharma, S., Paulo, J. A., Gulka, A. O. D., Boeszoermenyi, A., Zhang, J., Lombana, J. M., Palmieri, C. M., Laviolette, L. A., Arthanari, H., et al. (2021) · iScience · doi:10.1016/j.isci.2021.103338 · Cited by 3
Does mTORC1 inhibit autophagy at dual stages?
Santhaseela, A. R., & Jayavelu, T. (2020) · Bioessays · doi:10.1002/bies.202000187 · Cited by 3
“leucine and arginine in the cytosol towards mTORC1 recruitment to lysosomes is mediated by GATOR1-GATOR2 complexes.[27,28] In the presence of amino acids, theGATOR2 complex seems to associatewith and impair GATOR1 thereby inducing GTP-loading on RagA/B and activating mTORC1.”
BackgroundTOPDRIVER: the novel identifier of cancer driver genes in Gastric cancer and Melanoma
Razavi, S. M., Rami, F., Razavi, H., & Eslahchi, C. (2019) · Applied Network Science · doi:10.1007/s41109-019-0200-x · Cited by 4
Partial deletion of DEPDC 5 in a child with focal epilepsy
Bonaglia, M. C., Giorda, R., Epifanio, R., Bertuzzo, S., Marelli, S., Gérard, M., Andrieux, J., Zanotta, N., & Zucca, C. (2016) · Epilepsia Open · doi:10.1002/epi4.12012 · Cited by 3
“The DEP domain-containing protein 5 (DEPDC5) gene is a component of the GATOR1 complex, a critical negative regulator of the mammalian target of rapamycin (mTOR) pathway.(1) DEPDC5 loss-of-function mutations have recently been identified in a broad spectrum of epileptic syndromes with different brain localization and…”
BackgroundYang, E., Wang, G., Yang, J., Zhou, B., Tian, Y., & Cai, J. J. (2015) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/026393 · Cited by 2
“Rs1018804 is associated with WDR24 that encodes WD repeat-containing protein 24, a key component of Raginteracting complex essential for the activation of mTORC1 [43].”
BackgroundKosach, V., Cherednyk, O. V., & Хоруженко, А. І. (2015) · Biopolymers and Cell · doi:10.7124/bc.0008c7 · Cited by 3
“TSC1– TSC2 acts as a GTPase activating protein (GAP) for RHEB and promotes its loading with GDP. Aktmediated phosphorylation of TSC2 inhibits GAP activity of the TSC1–TSC2 complex and induces RHEB to bind GTP.”
BackgroundProgress of Autophagy in Epilepsy Research
Mo, J., Hu, J., & Cheng, X.-L. (2022) · The Journal of Bioscience and Medicine · doi:10.4236/jbm.2022.1010015 · Cited by 3
Ferguson, T. D. (2020) · doi:10.13023/etd.2020.459 · Cited by 3
“GATOR1 is tethered to the surface of lysosomes by the KICSTOR complex and has an inhibitory effect on mTORC1 by acting as a GAP for RagA/B. GATOR2 interacts with the tethered GATOR1 and is a positive regulator of mTORC1 signaling (Bar-Peled et al., 2013).”
BackgroundEl-Daly, M., Ibrahim, H., Labib, E., Ghanem, H., El-Elaimy, I., & Abdel-hamid, M. (2019) · Eurasian Journal of Medicine and Oncology · doi:10.14744/ejmo.2019.90638 · Cited by 3
Thomas, H. E., Veiga, S. R., Thomas, G., & Kozma, S. C. (2015) · Springer eBooks · doi:10.1007/978-2-8178-0492-7_2 · Cited by 1
Daley‐Bauer, L. P., Flantzer, L., Kyu, S. Y., Godoy, A., Weinberg, J., Marconi, V. C., Jones, D. P., & Younes, S. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1852583 · Cited by 1
Avl9 defines a family of GTPase-activating proteins that regulate diverse cell biological functions
Vignogna, R. C., & Fromme, J. (2026) · bioRxiv · doi:10.64898/2026.01.05.697756 · Cited by 2
“In contrast to the monomeric DENN domain proteins, three multimeric complexes that contain pairs of DENN domain protein subunits are known to function as GAPs: GATOR1 (a Rag-GAP) 59 , FLCN:FNIP (a Rag-GAP) 60,61 , and C9ORF72:SMCR8 (an Arf-GAP) 62,63 .”
Groff, K. J., Liang, Y.-N., Morici, C., Modasia, J. B., Mehendale, L., Gupta, N., D’Amore, A., Choe, Y., Hameed, M. Q., Rotenberg, A., et al. (2025) · JCI Insight · doi:10.1172/jci.insight.181544 · Cited by 2
“DEPDC5 inactivation leads to mTORC1 hyperactivity both in vivo and in vitro (6, 7).”
The Central FacilitaTOR: Coordinating Transcription and Translation in Eukaryotes
Adams-Brown, S. E., & Reid, K. Z. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26072845 · Cited by 2
“Additionally, TORC2 has a unique, rapamycin-insensitive role in actin cytoskeleton reorganization, first identified in yeast but later found in other higher eukaryotes, including humans [17,51,52].”
Wang, X.-Y., Liu, T., Sheng, Y.-Y., Qiu, C., Zhang, Y.-Z., Liu, Y.-Q., & Wu, C.-N. (2025) · Frontiers in Genetics · doi:10.3389/fgene.2025.1513675 · Cited by 2
Liu, J., Huang, R., Tang, F., Ma, Y., & Kwan, P. (2025) · Neurobiology of Disease · doi:10.1016/j.nbd.2025.106842 · Cited by 3
Gao, J., Lin, M., Qing, J.-N., Li, H., Zeng, X., Yuan, W., Li, T., & He, S. (2024) · The FASEB Journal · doi:10.1096/fj.202401352r · Cited by 2
“7,9,10 13 Emerging evidence has shown that protein ubiquitination plays an important role in regulating mTORC1 activity.”
The convergence of mTOR signaling and ethanol teratogenesis
Tucker, S. K., & Eberhart, J. K. (2024) · Reproductive Toxicology · doi:10.1016/j.reprotox.2024.108720 · Cited by 3
Forkel, D. S., Ibazebo, O., Soha, S. A., Bautista, S. J., Impellizzeri, S., Botelho, R. J., Hesketh, G. G., Gingras, A., & Antonescu, C. N. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.04.09.588669 · Cited by 2
“Central among these is the GATOR1 complex 8,9 , which contains the subunits DEPDC5, NPRL3, and NPRL2, the latter harboring GAP activity towards the GTPases RagA/B 10 .”
BackgroundLiu, X.-M., Nishikubo, K., Ohgaki, R., Okanishi, H., Okuda, S., Xu, M.-H., & Kanai, Y. (2024) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2024.02.012 · Cited by 2
Semanchik, P. L., Wesolowski, L. T., Ryan, P. J., White-Springer, S. H., & Fluckey, J. D. (2023) · Journal of Equine Veterinary Science · doi:10.1016/j.jevs.2023.104281 · Cited by 3
An affinity tool for the isolation of endogenous active mTORC1 from various cellular sources
Ibrahim, Y. H., Pantelios, S., & Mutvei, A. P. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.104644 · Cited by 2
“In their active state, RagA/B is bound to GTP and RagC/D is bound to GDP and strongly bind Raptor, thereby translocating mTORC1 to the lysosomal surface (9, 10, 12).”
BackgroundBelliveau, N. M., Footer, M. J., Akdoǧan, E., van Loon, A. P., Collins, S. R., & Theriot, J. (2022) · bioRxiv · doi:10.1101/2022.12.16.520717 · Cited by 2
Schmeisser, K., Kaptan, D., Raghuraman, B. K., Shevchenko, A., Penkov, S., & Kurzchalia, T. (2022) · bioRxiv · doi:10.1101/2022.08.26.505407 · Cited by 2
“The NPRL-2/NPRL-3 complex, similar to its mammalian orthologue GATOR1, represses mTORC1 and loss of either NPRLs causes a robust mTORC1 hyperactivation [38].”
BackgroundWhat is the impact of a novel DEPDC5 variant on an infant with focal epilepsy: a case report
Gu, C.-Y., Lu, X.-W., Ma, J., Pu, L., Zhi, X., Shu, J., Li, D., & Cai, C. (2022) · BMC Pediatrics · doi:10.1186/s12887-022-03515-8 · Cited by 2
“They work together and regulate mammalian target of rapamycin complex 1 (mTORC1) negatively [2].”
BackgroundBuddham, R., Chauhan, S., Narad, P., & Mathur, P. (2022) · Journal of Microbiology and Biotechnology · doi:10.4014/jmb.2108.08007 · Cited by 2
“Multiple complexes, including the v-ATPase, Ragulator, the Rag GTPase, and GATOR1/2, work together to modulate this process [15, 16].”
BackgroundLamming, D. (2021) · doi:10.20944/preprints202102.0491.v1 · Cited by 2
“When leucine levels are low, the Sestrin family of proteins binds to and inhibit the action of GATOR2 permitting GATOR1 to inhibit the recruitment of mTORC1 to the lysosome.”
BackgroundInfluentialGenetic dissection of Ragulator structure and function in amino acid-dependent regulation of mTORC1.
Nada, S., & Okada, M. (2020) · Journal of Biochemistry (Tokyo) · doi:10.1093/jb/mvaa076 · Cited by 2
Structure of the lysosomal SCARF (L-SCARF) complex, an Arf GAP haploinsufficient in ALS and FTD
Su, M.-Y., Zoncu, R., & Hurley, J. (2020) · bioRxiv · doi:10.1101/2020.04.15.042515 · Cited by 2
Wei, Z., Wang, L., Qiao, X., Zhang, Y., Liu, C., & Deng, Y. (2020) · Acta Epileptologica · doi:10.1186/s42494-020-0011-9 · Cited by 4
Jansen, L. (2018) · Epilepsy Currents · doi:10.5698/1535-7597.18.3.197 · Cited by 2
New Genes for Epilepsy–Autism Comorbidity
Ishii, A., & Hirose, S. (2017) · Journal of Pediatric Neurology online · doi:10.1055/s-0037-1602822 · Cited by 2
Molecular Processes and Regulation of Autophagy
Nasb, M., Kirberger, M., & Chen, N. (2021) · Springer eBooks · doi:10.1007/978-981-16-4525-9_1 · Cited by 3
Massimo, P. (2016) · doi:10.3389/conf.fnagi.2016.03.00039 · Cited by 2
“Trojan” Methionine Probe Reveals PKM2 as a Methionine-Sensing Protein in the mTORC1 Pathway
Sang, Z., Zheng, Y., Wang, X., Wu, C., Zhao, J., Wang, J. J., Sui, S., & Wang, J. (2026) · Journal of the American Chemical Society · doi:10.1021/jacs.6c06772 · Cited by 1
Hadj-Aissa, I., Muller, M., Soliz, J., Sephton, C. F., & Dutchak, P. A. (2026) · EMBO Reports · doi:10.1038/s44319-026-00846-w · Cited by 2
Cardiac remodeling and arrhythmia in a mouse model of Depdc5 haploinsufficiency
Ramos-Mondragón, R., Wang, S., Liu, Q., Chen, C.-L., Greiner, A., Marx, A., Shih, M.-Y., Parent, J. M., London, B., & Isom, L. L. (2026) · Epilepsia · doi:10.1002/epi.70244 · Cited by 1
Graded activation of the CLEAR network through mTORC1 suppression on cargo-harboring lysosomes
Hsieh, C., Chen, G.-C., & Yang, W. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.117228 · Cited by 1
Lysosomal phosphoinositide turnover acts upstream of RagGTPase–mTORC1 and controls muscle growth
Picot, M., Hifdi, N., Vaucourt, M., Mansat, M., Li, P., Singer, I. I., Chicanne, G., Stella, A., Shen, K., Miceli, C., et al. (2026) · Nature Metabolism · doi:10.1038/s42255-026-01484-1 · Cited by 1
“This includes the late endosomal/lysosomal adaptor and MAPK and mTOR activator (LAMTOR)/Ragulator complex (LAMTOR1–5) 2 , GATOR1 8,9 , SLC38A9 10 and FLCN–FNIP2 complexes 11,12 .”
Hablase, R., Sisu, C., Karteris, E., & Chatterjee, J. (2026) · Cancers · doi:10.3390/cancers18050866 · Cited by 1
The rapamycin sTORy: 50-year journey from Easter Island to the frontiers of biology and medicine
Xiao, X., & Dokudovskaya, S. (2026) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2026.02.004 · Cited by 4
Molecular and structural mechanisms of nutrient sensing in the mTORC1 pathway
Yang, S., Bian, T., & Zoncu, R. (2026) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2026.02.009 · Cited by 3
Besse, A., Kraus, M., Totu, T., Buljan, M., Janssen, A. P. A., van der Stelt, M., Matisikova, K., Veprkova, J., Sedlarikova, L., Jurinakova, T., et al. (2025) · Haematologica · doi:10.3324/haematol.2025.289245 · Cited by 1
“36 Given these insights, the highly active mTORC1 complex appears to be crucial for the cytotoxicity of ceritinib.”
Padilla, C. M., Lim, J., Lipinski, A. A., Langlais, P. R., & Capaldi, A. P. (2025) · Nature Communications · doi:10.1038/s41467-025-66907-1 · Cited by 2
Wang, X., Xiao, X., Situ, J., Xu, Q., Zhang, J., Xu, W., You, D., Ju, Y., Zhou, Y., Jiang, J., et al. (2025) · Medicine · doi:10.1097/md.0000000000045869 · Cited by 1
“[35,36] During aging, mTORC1 activation promotes increased expression of sodium channels (Scn1a), alters cell membrane potential, and induces depolarization of pre-osteoblasts, accelerating their aging.”
Fernandes, L., & Saccenti, E. (2025) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2025.195119 · Cited by 1
Intrinsic NPRL2 and NPRL3 regulate the sensitivity of B-cell malignancies to CAR-T cell therapy.
Han, F., Lu, Y.-T., Zhang, Y.-P., Ma, X., Tong, C., Wei, J.-S., Guo, Y.-L., Liu, C., Wu, Z.-Q., Han, W.-D., et al. (2025) · Journal of genetics and genomics = Yi chuan xue bao · doi:10.1016/j.jgg.2025.11.007 · Cited by 1
Shin, J., Tighanimine, K., Cormerais, Y., Rosenthal, D. M., Niroula, P., Lapp, S. C., Kalafut, K. C., Cissé, M. Y., Schrötter, S., & Manning, B. D. (2025) · iScience · doi:10.1016/j.isci.2025.114204 · Cited by 3
“6,7 The amino acid-dependent recruitment of mTORC1 to the lysosome through the Rag GTPases is essential for both the basal activation of mTORC1 and its ability to be regulated by growth factors.”
Oka, T., Okubo, R., Motomura, E., & Okada, M. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26199671 · Cited by 1
Amino acid–dependent TSC2 dephosphorylation by lysosome–PP2A regulates mTORC1 signaling transduction
Nakamura, T., Nada, S., Matsumoto, M., Othman, N. L., Kosako, H., Ikeda, K., Koshikawa, N., Masumoto, J., Sawasaki, T., Takekawa, M., et al. (2025) · Life Science Alliance · doi:10.26508/lsa.202503206 · Cited by 1
“The association of GATOR2 with GATOR1 (DEPDC5, NPRL2, and NPRL3), a GAP for Rag GTPases (Bar-Peled et al, 2013), inhibits GATOR1, leading to an increase in active Rag GTP .”
Cerullo, M., Canevari, C., Marte, A., Bacq, A., Fusco, A. D., Maletic, M., Baulac, S., & Benfenati, F. (2025) · Neurobiology of Disease · doi:10.1016/j.nbd.2025.106985 · Cited by 1
The role of serendipity in our investigation of embryo implantation
Sutherland, A. (2025) · Developmental Biology · doi:10.1016/j.ydbio.2025.01.010 · Cited by 1
Amino acids and KLHL22 do not activate mTORC1 via DEPDC5 degradation
Valenstein, M. L., Lalgudi, P. V., Kedir, J. F., Condon, K. J., Platzek, A., Freund, D., Taylor, M. S., Xu, Y., Chivukula, R., & Sabatini, D. M. (2025) · Nature · doi:10.1038/s41586-024-07974-0 · Cited by 1
Self-citationYe, W., Sun, L., Fu, C., Dong, H., & Zhou, T. (2024) · Health Science Reports · doi:10.1002/hsr2.70236 · Cited by 1
Feeding cancer to death - a triad of aromatic acids reduces tumor growth
Xavier, A., & D̵ikić, I. (2024) · Cell Death and Differentiation · doi:10.1038/s41418-024-01372-9 · Cited by 1
“The essential complexes GATOR1 and GATOR2 receive signals from cytosolic leucine and arginine and regulate mTOR activity [5].”
BackgroundIctal Bradycardia and Asystole in Sleep-Related Hypermotor Epilepsy: A Study of 200 Patients
Muccioli, L., Bruschi, G., Ferri, L., Scarabello, A., Taruffi, L., Vito, L. D., Mostacci, B., Provini, F., Calandra-Buonaura, G., Tinuper, P., et al. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13061767 · Cited by 1
“Genetic causes include pathogenic variants in genes encoding components of the GATOR1 complex, a negative regulator of mTOR ( DEPDC5 , less frequently NPRL2 or NPRL3 ), in acetylcholine receptor subunit genes ( CHRNA4 , less frequently CHRNB2 or CHRNA2 ), and in KCNT1 [3–5].”
BackgroundGenome-wide CRISPRi Screen in Human iNeurons to Identify Novel Focal Cortical Dysplasia GenesPreprint
Tidball, A. M., Luo, J.-H., Walker, J., Takla, T., Carvill, G., & Parent, J. M. (2023) · bioRxiv · doi:10.1101/2023.12.13.571474 · Cited by 1
“DEPDC5 is the most common known cause of FCD and focal epilepsy and is a negative regulator of mTOR signaling in response to the concentrations of specific amino acids (23, 24).”
Fernandes, S. A., Angelidaki, D.-D., Nüchel, J., Pan, J., Gollwitzer, P., Elkis, Y., Artoni, F., Wilhelm, S., Kovacevic-Sarmiento, M., & Demetriades, C. (2023) · bioRxiv · doi:10.1101/2023.10.03.559930 · Cited by 1
Genetic Factors of Reflex Epilepsies
Dudko, N. A., Kunizheva, S. S., Andreeva, T. V., Adrianova, I., & Rogaev, E. (2023) · Russian Journal of Genetics · doi:10.1134/s1022795423100046 · Cited by 1
“Thus, mutations in the gene DEPDC5 , up to 5% of the cases considered in the study, led to a shift in the reading frame, which could have led to disturbances in the functioning of the protein, which is an inhibitor of the pathway rapamycin (mTOR) [96].”
BackgroundYULINK regulates vascular formation in zebrafish and HUVECs
Lin, H., Kuo, M.-W., Fan, T.-C., Yu, A. L.-T., & Yu, J. (2023) · Biological Research · doi:10.1186/s40659-023-00415-8 · Cited by 1
“It was also found in human HEK-293 T cells that YULINK is a subunit of GATOR2 complex proteins and inhibition of GATOR2 suppressed mTORC1 signaling [12].”
BackgroundThe Role of Sestrins in the Regulation of the Cellular Response to Stress
Budanov, A. V. (2022) · Biology Bulletin Reviews · doi:10.1134/s2079086422040028 · Cited by 1
“GATOR1, which is composed of the Nprl2, Nprl3, and DEPDC5 proteins, functions as a GAP for RagA/B (Bar-Peled et al., 2013).”
BackgroundInfluentialFarhan, H., Abougabal, K., Gaber, H., & Attia, D. (2022) · Egyptian Journal of Immunology · doi:10.55133/eji.290305 · Cited by 1
“8, 15 The consequent increased activity of the mTOR pathway promotes fibrosis through transforming growth factor-β (TGF-β) independent mechanism, 17 which is considered as another explanation of the molecular basis of genetic association of DEPDC5 variants with fibrosis progression.”
Phytochemical based sestrin2 pharmacological modulators in the treatment of adenocarcinomas
Alausa, A. O., Victor, U. C., Celestine, U. O., Eweje, I. A., Balogun, T. A., Adeyemi, R. O., Olatinwo, M., Ogunlana, A. T., Oladipo, O. O., & Olaleke, B. (2021) · Phytomedicine Plus · doi:10.1016/j.phyplu.2021.100133 · Cited by 2
THE THERAPEUTIC VALUE OF LYSINE AGAINST CANCER: A COMPREHENSIVE REVIEW
Debnath, S., Mukherjee, A., Karan, S., Chatterjee, T., Tapan, K., Chatterjee, T., Chatterjee, T., Al, Cantor, J., Sabatini, D., et al. (2020) · International Journal of Biology Pharmacy and Allied Sciences · doi:10.31032/ijbpas/2020/9.12.5181 · Cited by 1
Self-citationGonzalez-Estevez, A., Verrico, A., Orniacki, C., Reina-San-Martin, B., & Doye, V. (2020) · doi:10.1101/2020.10.27.357376 · Cited by 1
“Mios is not required for proper cell growth and cell differentiation in mESCs Within the GATOR2 complex, Seh1 directly interacts with Mios (also known as Mio, missing oocyte in Drosophila and Sea4 in budding yeast) (Senger et al., 2011; Bar-Peled et al., 2013; Algret et al., 2014).”
BackgroundMethodInfluentialSURO-2/TMEM39 Facilitates Collagen Secretion through the Formation of Large COPII VesiclesPreprint
Lee, K., Sung, J. Y., Lee, S., Lim, G., Jung, K., Chung, J., Jung, H., Kim, Y., & Shim, J. (2020) · doi:10.21203/rs.3.rs-35924/v1 · Cited by 1
Proposed Mechanisms Underlying the Interference Effect
Ellefsen, S., & Baar, K. (2018) · Springer eBooks · doi:10.1007/978-3-319-75547-2_7 · Cited by 2
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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