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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CG12090 is the Drosophila ortholog of mammalian DEPDC5, which was found to be part of the GATOR1 complex that inhibits the Tor pathway.
“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]
The paper identifies DEPDC5 as a GATOR1 component (passage 7, section labeled Abstract) and reports that loss of dDEPDC5 prevents normal inactivation of Drosophila TORC1 during amino acid deprivation (passage 1, same section). Our copy does not identify dDEPDC5 as CG12090, so it does not verify that specific gene-to-ortholog mapping. (LLM, conf=0.86)
Experimental — accuracy not yet measuredWDR59 and WDR24 are both subunits of GATOR2 complex, which functions as a positive regulator of amino-acid-mediated mTORC1 activation.
“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 ( <scp>SOMMA</scp> ) (2024) · cites this paper as Bar‐Peled et al., 2013
Mutants in GATOR1 subunits promote cell growth by increasing Tor activity.
“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]
At the Ragulator, the Rag heterodimer interacts with GATOR, an octomeric complex that controls the activity of the Rag proteins.
“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]
Upstream regulation of the Rag GTPases features at least four large protein complexes: GATOR1, a GAP for RagA/RagB/Gtr1; FLCN-FNIP, a GAP for RagC/RagD/Gtr2; GATOR2, an inhibitor of GATOR1; and KICSTOR, which is thought to regulate the GATOR complexes.
“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× · see citing works
“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 · see citing works
Self-citationPhosphorylation 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 · see citing works
Self-citationKim, 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
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× · see citing works
“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× · see citing works
“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 · see citing works
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 2,003 · see citing works
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× · see citing works
“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× · see citing works
“Nucleotide Exchange Assays These assays were essentially performed as described in (5).”
mTOR and cancer: insights into a complex relationship
Sabatini, D. M. (2006) · Nature Reviews Cancer · doi:10.1038/nrc1974 · Cited by 1,322 · see citing works
Self-citationEnhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR
Neshat, M., Mellinghoff, I., Tran, C., Stiles, B. L., Thomas, G., Petersen, R., Frost, P., Gibbons, J., Wu, H., & Sawyers, C. (2001) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.171076798 · Cited by 1,033 · see citing works
Ragulator Is a GEF for the Rag GTPases that Signal Amino Acid Levels to mTORC1
Bar-Peled, L., Schweitzer, L. D., Zoncu, R., & Sabatini, D. M. (2012) · Cell · doi:10.1016/j.cell.2012.07.032 · Cited by 918 · cited 1× · see citing works
“Lysis of HEK-293T cells stably expressing FLAG-tagged DEPDC5, WDR24 or Metap2, was identical to the procedure described in (7).”
Self-citationTarget of Rapamycin (TOR) in Nutrient Signaling and Growth Control
Loewith, R., & Hall, M. (2011) · Genetics · doi:10.1534/genetics.111.133363 · Cited by 894 · see citing works
Leucyl-tRNA Synthetase Is an Intracellular Leucine Sensor for the mTORC1-Signaling Pathway
Han, J. M., Jeong, S. J., Park, M. C., Kim, G., Kwon, N. H., Kim, H. K., Ha, S. H., Ryu, S. H., & Kim, S. (2012) · Cell · doi:10.1016/j.cell.2012.02.044 · Cited by 824 · see citing works
Lerman, M. I., & Minna, J. D. (2000) · PubMed · Cited by 537 · see citing works
Krengel, U., Schlichting, I., Scherer, A., Schumann, R., Frech, M., John, J., Kabsch, W., Pai, E., & Wittinghofer, A. (1994) · Cell · doi:10.1016/0092-8674(90)90018-a · Cited by 374 · see citing works
Novel G Proteins, Rag C and Rag D, Interact with GTP-binding Proteins, Rag A and Rag B*
Sekiguchi, T., Hirose, E., Nakashima, N., Ii, M., & Nishimoto, T. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m004389200 · Cited by 249 · see citing works
Wang, M. Y., Lu, K. V., Zhu, S., Dia, E. Q., Vivanco, I., Shackleford, G. M., Cavenee, W. K., Mellinghoff, I. K., Cloughesy, T. F., Sawyers, C. L., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-04-4392 · Cited by 240 · see citing works
A practical approach to crosslinking
Mattson, G., Conklin, E., Desai, S., Nielander, G., Savage, M., & Morgensen, S. (1993) · Molecular Biology Reports · doi:10.1007/bf00986726 · Cited by 231 · see citing works
PIK3CA/PTEN Mutations and Akt Activation as Markers of Sensitivity to Allosteric mTOR inhibitors
Meric-Bernstam, F., Akcakanat, A., Chen, H.-Q., Do, K., Sangai, T., Adkins, F. C., González-Angulo, A., Rashid, A., Crosby, K., Dong, M., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-2123 · Cited by 228 · see citing works
Mitochondria regulate autophagy by conserved signalling pathways
Graef, M., & Nunnari, J. (2011) · EMBO Journal · doi:10.1038/emboj.2011.104 · Cited by 189 · see citing works
Ji, L., Nishizaki, M., Gao, B., Burbee, D. G., Kondo, M., Kamibayashi, C., Xu, K., Yen, N., Atkinson, E. N., Fang, B., et al. (2002) · PubMed · Cited by 176 · see citing works
Neklesa, T. K., & Davis, R. W. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000515 · Cited by 151 · see citing works
Dokudovskaya, S., Waharte, F., Schlessinger, A., Pieper, U., Devos, D. P., Cristea, I. M., Williams, R., Salamero, J., Chait, B. T., Šali, A., et al. (2011) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m110.006478 · Cited by 145 · see citing works
Integrated genomic analyses of ovarian carcinoma
The Cancer Genome Atlas Research Network (2011) · Nature · doi:10.1038/nature10166 · Cited by 129 · see citing works
Self-citationWu, X., & Tu, B. P. (2011) · Molecular Biology of the Cell · doi:10.1091/mbc.e11-06-0525 · Cited by 98 · see citing works
Functional Characterization of the Candidate Tumor Suppressor Gene NPRL2/G21 Located in 3p21.3C
Li, J., Wang, F.-L., Haraldson, K., Protopopov, A., Duh, F., Geil, L., Kuzmin, I., Minna, J., Stanbridge, E., Braga, E., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-3869 · Cited by 78 · see citing works
Seng, T. J., Ichimura, K., Liu, L., Tingby, O., Pearson, D., & Collins, V. (2005) · Genes, Chromosomes and Cancer · doi:10.1002/gcc.20181 · Cited by 53 · see citing works
Iida, T., & Lilly, M. (2004) · Development · doi:10.1242/dev.01001 · Cited by 46 · see citing works
Membrane-coating lattice scaffolds in the nuclear pore and vesicle coats
Leksa, N., & Schwartz, T. (2010) · The Nucleus · doi:10.4161/nucl.1.4.11798 · Cited by 20 · see citing works
Flagged first, then by citations
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mTOR Signaling in Growth, Metabolism, and Disease
Saxton, R. A., & Sabatini, D. M. (2017) · Cell · doi:10.1016/j.cell.2017.02.004 · Cited by 7,555 · see citing works
“Several components of the nutrient sensing input to mTORC1 have also been implicated in cancer progression, including all three subunits of the GATOR1 complex, which are mutated with low frequency in glioblastoma (Bar-Peled et al., 2013), as well as RagC, which was recently found to be mutated at high frequency ( 18%)…”
BackgroundInfluentialSelf-citationmTOR Signaling in Growth, Metabolism, and Disease.
Saxton, R., & Sabatini, D. (2017) · Cell · doi:10.1016/j.cell.2017.03.035 · Cited by 3,889 · see citing works
“Several components of the nutrient sensing input to mTORC1 have also been implicated in cancer progression, including all three subunits of the GATOR1 complex, which are mutated with low frequency in glioblastoma (Bar-Peled et al., 2013), as well as RagC, which was recently found to be mutated at high frequency (~18%)…”
BackgroundInfluentialSelf-citationmTOR 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
Self-citationMTOR: a pharmacologic target for autophagy regulation
Kim, Y. C., & Guan, K.-L. (2015) · Journal of Clinical Investigation · doi:10.1172/jci73939 · Cited by 2,126 · see citing works
PI3K and cancer: lessons, challenges and opportunities
Fruman, D. A., & Rommel, C. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4204 · Cited by 1,716 · see citing works
Sestrin2 is a leucine sensor for the mTORC1 pathway
Wolfson, R. L., Chantranupong, L., Saxton, R. A., Shen, K., Scaria, S. M., Cantor, J. R., & Sabatini, D. M. (2016) · Science · doi:10.1126/science.aab2674 · Cited by 1,306 · see citing works
“Ragulator anchors the Rag heterodimers to the lysosome and has nucleotide exchange activity for RagA and RagB (21, 25).”
BackgroundInfluentialSelf-citationNutrient-sensing mechanisms and pathways
Efeyan, A., Comb, W. C., & Sabatini, D. M. (2015) · Nature · doi:10.1038/nature14190 · Cited by 1,110 · see citing works
Self-citationMaking new contacts: the mTOR network in metabolism and signalling crosstalk
Shimobayashi, M., & Hall, M. N. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3757 · Cited by 1,053 · see citing works
Whole-genome landscape of pancreatic neuroendocrine tumours
Initiative, A. P. C. G., Scarpa, A., Chang, D. K., Nones, K., Corbo, V., Patch, A.-M., Bailey, P., Lawlor, R. T., Johns, A. L., Miller, D. K., et al. (2017) · Nature · doi:10.1038/nature21063 · Cited by 999 · see citing works
Panwar, V., Singh, A., Bhatt, M., Tonk, R. K., Azizov, S., Raza, A. S., Sengupta, S., Kumar, D., & Garg, M. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01608-z · Cited by 967 · see citing works
“53 Sestrin2 was discovered as a GATOR2 interacting protein partner that senses cytosolic amino acid.”
BackgroundmTOR 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
The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway
Chantranupong, L., Scaria, S. M., Saxton, R. A., Gygi, M. P., Shen, K., Wyant, G. A., Wang, T., Harper, J. W., Gygi, S. P., & Sabatini, D. M. (2016) · Cell · doi:10.1016/j.cell.2016.02.035 · Cited by 843 · see citing works
“The GATOR2 complex, which has five subunits (mios, WDR24, WDR59, sec13, seh1L), acts upstream or parallel to GATOR1 and is a key positive regulator of the mTORC1 pathway, although its molecular function is unknown (Bar-Peled et al., 2013).”
Self-citationAMPK 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
Menon, S., Dibble, C. C., Talbott, G., Hoxhaj, G., Valvezan, A., Takahashi, H., Cantley, L., & Manning, B. (2014) · Cell · doi:10.1016/j.cell.2013.11.049 · Cited by 787 · 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
“Early experiments with Ragulator hinted at the auxiliary roles of this complex: Ragulator preferentially bound to Rags in their inactive state, an interaction that was driven by the nucleotide state of RagA/B (48).”
InfluentialSelf-citationTargeting mTOR for cancer therapy
Hua, H., Kong, Q.-B., Zhang, H., Wang, J., Luo, T., & Jiang, Y.-F. (2019) · Journal of Hematology & Oncology · doi:10.1186/s13045-019-0754-1 · Cited by 772 · see citing works
Wang, S., Tsun, Z., Wolfson, R. L., Shen, K., Wyant, G., Plovanich, M. E., Yuan, E. D., Jones, T. D., Chantranupong, L., Comb, W. C., et al. (2015) · Science · doi:10.1126/science.1257132 · Cited by 772 · see citing works
Self-citationRegulation 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
Differential regulation of mTORC1 by leucine and glutamine
Jewell, J. L., Kim, Y. C., Russell, R. C., Yu, F.-X., Park, H. W., Plouffe, S. W., Tagliabracci, V. S., & Guan, K.-L. (2015) · Science · doi:10.1126/science.1259472 · Cited by 757 · see citing works
The role of ubiquitination in tumorigenesis and targeted drug discovery
Deng, L., Meng, T., Chen, L., Wei, W., & Wang, P. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-0107-0 · Cited by 744 · see citing works
“Moreover, many regulators of RagA/B have been identified, and these include the SLC38A9 functioning as the guanosine exchange factor (GEF) of RagA/B,(128) Sestrin2 identified as the guanine nucleotide dissociation inhibitor (GDI) of RagA/B,(129) and the GATOR1 complex acting as a GTPaseactivating protein (GAP) to RagA…”
BackgroundRegulation 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
Lipton, J. O., & Şahin, M. (2014) · Neuron · doi:10.1016/j.neuron.2014.09.034 · Cited by 732 · see citing works
“Human mutations in DEPDC5, a component of the GATOR complex, have been linked to both epilepsy with cerebral malformations and nonlesional epilepsy (Bar-Peled et al., 2013; Dibbens et al., 2013; Scheffer et al., 2014).”
Nutrient sensing and TOR signaling in yeast and mammals
González, A., & Hall, M. (2017) · EMBO Journal · doi:10.15252/embj.201696010 · Cited by 684 · see citing works
“GATOR1 is composed of DEPDC5 (DEP domain-containing protein 5), NPRL2 (nitrogen permease regulator 2-like protein), and NPRL3 where DEPDC5 is thought to possess the GAP activity toward RAGA/B (Bar-Peled et al , 2013; Panchaud et al , 2013a).”
InfluentialSLC38A9 is a component of the lysosomal amino acid sensing machinery that controls mTORC1
Rebsamen, M., Pochini, L., Stasyk, T., de Araújo, M. E. G., Galluccio, M., Kandasamy, R. K., Snijder, B., Fauster, A., Rudashevskaya, E. L., Bruckner, M., et al. (2015) · Nature · doi:10.1038/nature14107 · Cited by 673 · see citing works
Abu-Remaileh, M., Wyant, G. A., Kim, C., Laqtom, N. N., Abbasi, M., Chan, S. H., Freinkman, E., & Sabatini, D. M. (2017) · Science · doi:10.1126/science.aan6298 · Cited by 665 · see citing works
“Consistent with this possibility, in cells that lack functional GATOR1 (DEPDC5 KO cells) and thus have amino acid-insensitive mTORC1 signaling (18), amino acid starvation did decrease the concentrations of lysosomal amino acids (Fig.”
BackgroundSelf-citationNutrient sensing and signaling in the yeast Saccharomyces cerevisiae
Conrad, M., Schothorst, J., Kankipati, H., Zeebroeck, G. V., Rubio‐Texeira, M., & Thevelein, J. (2014) · FEMS Microbiology Reviews · doi:10.1111/1574-6976.12065 · Cited by 616 · see citing works
“The GAP activity of SEACIT is also conserved, as the orthologous complex in Drosophila and human cells, known as GATOR1, also acts as a GAP toward RagA and RagB (Bar-Peled et al., 2013).”
BackgroundNguyen, T. B., Louie, S. M., Daniele, J. R., Tran, Q., Dillin, A., Zoncu, R., Nomura, D. K., & Olzmann, J. A. (2017) · Developmental Cell · doi:10.1016/j.devcel.2017.06.003 · Cited by 610 · see citing works
“Cancer cell lines HCC1500 and SW780, which lack Nprl2 and exhibit decreased mTOR nutrient responsiveness (Bar-Peled et al., 2013) (Figure S4B), also showed reduced LD biogenesis during HBSS starvation (Figures S4C and S4D).”
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
The Lysosome as a Regulatory Hub
Perera, R. M., & Zoncu, R. (2016) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-111315-125125 · Cited by 664 · see citing works
“Studies in mammalian cells led to the identification of the GATOR1 complex as the GAP that inactivates RagA/B. Depletion of any of the three GATOR1 subunits leads to constitutive lysosomal localization and to activation of mTORC1 irrespective of amino acid status (Bar-Peled et al. 2013).”
BackgroundAmino Assets: How Amino Acids Support Immunity
Kelly, B. L., & Pearce, E. L. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.06.010 · Cited by 653 · see citing works
Tsun, Z.-Y., Bar-Peled, L., Chantranupong, L., Zoncu, R., Wang, T., Kim, C., Spooner, E., & Sabatini, D. M. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.09.016 · Cited by 565 · see citing works
“…mg HA-GST-RagCD181N and 16 mg HA-RagB; 8 mg HA-GST-RagC and 16 mg HA-RagB; GATOR1: 4 mg FLAGDEPDC5 and 8 mg myc-NPRL2 and 8 mg myc-NPRL3 isoform 1 (Bar-Peled et al., 2013); FLCN-FNIP1: 8 mg FLAG-FNIP1 and 16 mg HA-FLCN; FLCNFNIP2: 8 mg FLAG-FNIP2 and 16 mg HA-FLCN; FLCN(DN-term)-FNIP2: 8 mg…”
InfluentialSelf-citationZhang, C., Jiang, B., Li, M., Zhu, M., Peng, Y., Zhang, Y., Wu, Y., Li, T. Y., Yu, L., Lu, Z., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.06.014 · Cited by 546 · see citing works
“Termination of mTORC1 signaling is executed by GATOR1, which functions as the GAP of RAGA/RAGB; without GATOR1, mTORC1 is constitutively active and localized on the endosomal surface (Bar-Peled et al., 2013; Panchaud et al., 2013).”
BackgroundThe mechanistic target of rapamycin: the grand conducTOR of metabolism and aging
Kennedy, B. K., & Lamming, D. W. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.05.009 · Cited by 544 · see citing works
“Conversely, mTORC1 signaling is increased in many agerelated diseases and pathologies, including cancer (Bar-Peled et al., 2013; Grabiner et al., 2014), and may be linked to Hutch-”
SAMTOR is an S-adenosylmethionine sensor for the mTORC1 pathway
Gu, X., Orozco, J. M., Saxton, R., Condon, K. J., Liu, G. Y., Krawczyk, P. A., Scaria, S. M., Harper, J. W., Gygi, S., & Sabatini, D. (2017) · Science · doi:10.1126/science.aao3265 · Cited by 533 · see citing works
Self-citationWhere is mTOR and what is it doing there?
Betz, C., & Hall, M. (2013) · Journal of Cell Biology · doi:10.1083/jcb.201306041 · Cited by 529 · see citing works
“Zoncu et al. (2011) have proposed that amino acids are sensed in the lumen of the lysosome via the v-ATPase, which then activates Rag via Ragulator and possibly the recently described Rag GAPs (Bar-Peled et al., 2013; Panchaud et al., 2013; Petit et al., 2013; Tsun et al., 2013).”
mTORC1 as the main gateway to autophagy
Rabanal-Ruiz, Y., Otten, E. G., & Korolchuk, V. (2017) · Essays in Biochemistry · doi:10.1042/ebc20170027 · Cited by 505 · see citing works
The dawn of the age of amino acid sensors for the mTORC1 pathway
Wolfson, R. L., & Sabatini, D. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.07.001 · Cited by 500 · see citing works
“Folliculin and its binding partners, FNIP1/2, have GAP activity towards RagC/D (Tsun et al., 2013), while GATOR1 (GAP activity towards the Rags 1) is a GAP for RagA/B (Bar-Peled et al., 2013).”
InfluentialSelf-citationHan, K., Jeng, E., Hess, G., Morgens, D., Li, A., & Bassik, M. (2017) · Nature Biotechnology · doi:10.1038/nbt.3834 · Cited by 482 · see citing works
Chantranupong, L., Wolfson, R. L., Orozco, J. M., Saxton, R. A., Scaria, S. M., Bar-Peled, L., Spooner, E., Isasa, M., Gygi, S. P., & Sabatini, D. M. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.09.014 · Cited by 466 · see citing works
“The GATOR2 complex, which has five known subunits (WDR24, WDR59, Mios, Sec13, and Seh1L), is a positive component of the pathway and upstream of or parallel to GATOR1, but its molecular function is unknown (Bar-Peled et al., 2013).”
InfluentialSelf-citationStructural basis for leucine sensing by the Sestrin2-mTORC1 pathway
Saxton, R. A., Knockenhauer, K. E., Wolfson, R. L., Chantranupong, L., Pacold, M. E., Wang, T., Schwartz, T. U., & Sabatini, D. M. (2016) · Science · doi:10.1126/science.aad2087 · Cited by 457 · see citing works
Self-citationThe Structure of the Nuclear Pore Complex (An Update)
Lin, D. H., & Hoelz, A. (2019) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-062917-011901 · Cited by 449 · see citing works
Twenty-five years of mTOR: Uncovering the link from nutrients to growth
Sabatini, D. (2017) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1716173114 · Cited by 448 · see citing works
Self-citationInsulin signaling in health and disease
Saltiel, A. R. (2021) · Journal of Clinical Investigation · doi:10.1172/jci142241 · Cited by 446 · see citing works
“Akt phosphorylates and inhibits the GTPase-activating protein (GAP) tuberosclerosis complex 2 (TSC2), which forms a complex with the scaffolding protein TSC1 that negatively controls the small GTPase Rheb, a key regulator of the mTORC1 complex (120, 121).”
BackgroundWyant, G., Abu-Remaileh, M., Wolfson, R. L., Chen, W. W., Freinkman, E., Danai, L. V., Heiden, M. V. V., & Sabatini, D. (2017) · Cell · doi:10.1016/j.cell.2017.09.046 · Cited by 434 · see citing works
“(B) In cells lacking DEPDC5, a component of GATOR1, mTORC1 signaling is insensitive to deprivation of all amino acids, leucine, or arginine as assessed by the phosphorylation of S6K1.”
InfluentialSelf-citationmTOR and autophagy: a dynamic relationship governed by nutrients and energy.
Dunlop, E., & Tee, A. (2014) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2014.08.006 · Cited by 428 · see citing works
Lysosome biogenesis: Regulation and functions
Yang, C., & Wang, X.-C. (2021) · Journal of Cell Biology · doi:10.1083/jcb.202102001 · Cited by 420 · see citing works
“The multi-subunit complex Ragulator and GATOR1 were respectively identified as the guanine exchange factor and GTPase activating protein (GAP) of RagA/B (Bar-Peled et al., 2013; Bar-Peled et al., 2012).”
BackgroundInfluentialGrabiner, 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
Self-citationRegulation of TORC1 in response to amino acid starvation via lysosomal recruitment of TSC2
Demetriades, C., Doumpas, N., & Teleman, A. A. (2014) · Cell · doi:10.1016/j.cell.2014.01.024 · Cited by 412 · 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
The Emerging Role of Branched-Chain Amino Acids in Insulin Resistance and Metabolism
Yoon, M.-S. (2016) · Nutrients · doi:10.3390/nu8070405 · Cited by 395 · 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
Potential Mechanisms Connecting Purine Metabolism and Cancer Therapy
Yin, J., Ren, W., Huang, X.-G., Deng, J.-P., Li, T.-J., & Yin, Y.-L. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01697 · Cited by 379 · 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
“167 ,168).”
The mTOR signalling cascade: paving new roads to cure neurological disease
Crino, P. B. (2016) · Nature Reviews Neurology · doi:10.1038/nrneurol.2016.81 · Cited by 368 · see citing works
Recruitment of folliculin to lysosomes supports the amino acid–dependent activation of Rag GTPases
Petit, C. S., Roczniak-Ferguson, A., & Ferguson, S. M. (2013) · Journal of Cell Biology · doi:10.1083/jcb.201307084 · Cited by 355 · see citing works
Sestrins inhibit mTORC1 kinase activation through the GATOR complex
Parmigiani, A., Nourbakhsh, A., Ding, B., Wang, W., Kim, Y. C., Akopiants, K., Guan, K.-L., Karin, M., & Budanov, A. V. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.10.019 · Cited by 336 · see citing works
“RagA:RagB is active in its GTP-bound form, and GATOR1 can regulate RagA:RagB by stimulating its GTPase activity (Bar-Peled et al., 2013).”
BackgroundInfluentialmTOR in Brain Physiology and Pathologies
Bockaert, J., & Marin, P. (2015) · Physiological Reviews · doi:10.1152/physrev.00038.2014 · Cited by 360 · see citing works
“mTORC1 activation due to mutations in DEPDC5 [a component of the GATOR1 complex which negatively controls mTORC1 activity (18)] has also been implicated in a majority of cases of autosomal dominant familial focal epilepsies with variable foci (FFEVF) (63).”
BackgroundActivation of mTOR (mechanistic target of rapamycin) in rheumatic diseases
Perl, A. (2015) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2015.172 · Cited by 335 · see citing works
Regulation of Autophagy by mTOR Signaling Pathway.
Wang, Y., & Zhang, H.-B. (2019) · Advances in Experimental Medicine and Biology · doi:10.1007/978-981-15-0602-4_3 · Cited by 318 · see citing works
A systems study reveals concurrent activation of AMPK and mTOR by amino acids
Pezze, P. D., Ruf, S., Sonntag, A. G., Langelaar-Makkinje, M., Hall, P., Heberle, A., Navas, P., van Eunen, K., Tölle, R. C., Schwarz, J. J., et al. (2016) · Nature Communications · doi:10.1038/ncomms13254 · Cited by 315 · see citing works
KICSTOR recruits GATOR1 to the lysosome and is necessary for nutrients to regulate mTORC1
Wolfson, R. L., Chantranupong, L., Wyant, G., Gu, X., Orozco, J. M., Shen, K., Condon, K. J., Petri, S., Kedir, J. F., Scaria, S. M., et al. (2017) · Nature · doi:10.1038/nature21423 · Cited by 308 · see citing works
Self-citationSLC38A2 and glutamine signalling in cDC1s dictate anti-tumour immunity
Guo, C., You, Z., Shi, H., Sun, Y., Du, X.-R., Palacios, G., Guy, C., Yuan, S.-J., Chapman, N. M., Lim, S., et al. (2023) · Nature · doi:10.1038/s41586-023-06299-8 · Cited by 307 · see citing works
Mechanism of arginine sensing by CASTOR1 upstream of mTORC1
Saxton, R., Chantranupong, L., Knockenhauer, K., Schwartz, T., & Sabatini, D. (2016) · Nature · doi:10.1038/nature19079 · Cited by 301 · see citing works
Self-citationNutrient-Sensing Mechanisms across Evolution
Chantranupong, L., Wolfson, R. L., & Sabatini, D. M. (2015) · Cell · doi:10.1016/j.cell.2015.02.041 · Cited by 320 · see citing works
“Ragulator binds the Rag GTPases to the lysosome and also has nucleotide exchange activity for RagA/B (Bar-Peled et al., 2012; Sancak et al., 2010), but the function of the v-ATPase in the pathway is unknown.”
InfluentialSelf-citationGrowing knowledge of the mTOR signaling network
Huang, K., & Fingar, D. C. (2014) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2014.09.011 · Cited by 301 · 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
“The addition of amino acids triggers the shift of Rag GTPases to their active nucleotide-bound state, i.e., the GTP-bound form of RagA/B and the GDP-bound form of RagC/D. Active Rag GTPases can bind to Raptor and thereby recruit mTORC1 on the lysosomal surface, where Rheb, a direct activator of mTORC1, is also believe…”
BackgroundInfluentialThe role of mammalian target of rapamycin (mTOR) in insulin signaling
Yoon, M.-S. (2017) · Nutrients · doi:10.3390/nu9111176 · Cited by 300 · see citing works
The hidden genetics of epilepsy—a clinically important new paradigm
Thomas, R. H., & Berkovic, S. F. (2014) · Nature Reviews Neurology · doi:10.1038/nrneurol.2014.62 · Cited by 297 · see citing works
Nutrient regulation of mTORC1 at a glance
Condon, K. J., & Sabatini, D. (2019) · Journal of Cell Science · doi:10.1242/jcs.222570 · Cited by 288 · see citing works
Self-citationLim, C.-Y., Davis, O. B., Shin, H. R., Zhang, J., Berdan, C. A., Jiang, X.-T., Counihan, J. L., Ory, D., Nomura, D., & Zoncu, R. (2019) · Nature Cell Biology · doi:10.1038/s41556-019-0391-5 · Cited by 283 · 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
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
“GAP activity toward Rags 1 (GATOR1) is a heterotrimeric complex comprising of Nprl3, Nprl2, and DEPDC5, which acts as a RagA/B GAP and inhibits mTORC1 (81).”
BackgroundFamilial focal epilepsy with focal cortical dysplasia due to DEPDC5 mutations
Baulac, S., Ishida, S., Marsan, E., Miquel, C., Biraben, A., Nguyen, D., Nordli, D., Cossette, P., Nguyen, S., Lambrecq, V., et al. (2015) · Annals of Neurology · doi:10.1002/ana.24368 · Cited by 279 · see citing works
“The finding that DEPDC5 is associated with FCD in the context of inherited focal epilepsy agrees with evidence that DEPDC5 acts as an mTORC1 inhibitor.(16) The role of DEPDC5 in the mTORC1 cascade is particularly attractive for 2 main reasons: (1) other genes encoding inhibitors of mTORC1 have been shown to cause brai…”
BackgroundRab1A Is an mTORC1 Activator and a Colorectal Oncogene
Thomas, J. D., Zhang, Y.-J., Wei, Y.-H., Cho, J.-H., Morris, L. E., Wang, H.-Y., & Zheng, X. F. S. (2014) · Cancer Cell · doi:10.1016/j.ccell.2014.09.008 · Cited by 278 · see citing works
“A recent study implicated GATOR, the GTPase-activating protein (GAP) for Rag A/RagB as potential tumor suppressor (Bar-Peled et al., 2013).”
Phosphatidylinositol 3‐phosphates—at the interface between cell signalling and membrane traffic
Marat, A. L., & Haucke, V. (2016) · EMBO Journal · doi:10.15252/embj.201593564 · Cited by 278 · see citing works
“The recruitment of mTORC1 to the lysosome, where it will be activated, is mediated via the cellular amino acid status (Sancak et al , 2008; Zoncu et al , 2011a; Bar-Peled et al , 2013).”
Metformin as an Anticancer Agent
Vancura, A., Bu, P., Bhagwat, M., Zeng, J., & Vancurova, I. (2018) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2018.07.006 · Cited by 274 · see citing works
The lysosome as a command-and-control center for cellular metabolism
Lim, C.-Y., & Zoncu, R. (2016) · Journal of Cell Biology · doi:10.1083/jcb.201607005 · Cited by 274 · see citing works
“Npr3) GAT OR1 DEP DC5, Nprl2, Nprl3 GAP for Rag-A/B Down Dokudovskaya and Rout, 2011; Bar-Peled et al., 2013; Panchaud et al., 2013”
BackgroundDefinition and diagnostic criteria of sleep-related hypermotor epilepsy
Tinuper, P., Bisulli, F., Cross, J. H., Hesdorffer, D., Kahane, P., Nobili, L., Provini, F., Scheffer, I., Tassi, L., Vignatelli, L., et al. (2016) · Neurology · doi:10.1212/wnl.0000000000002666 · Cited by 274 · see citing works
Lysosomes as coordinators of cellular catabolism, metabolic signalling and organ physiology
Settembre, C., & Perera, R. M. (2023) · Nature reviews. Molecular cell biology · doi:10.1038/s41580-023-00676-x · Cited by 269 · see citing works
Signaling pathways in cancer metabolism: mechanisms and therapeutic targets
You, M., Xie, Z., Zhang, N., Zhang, Y., Xiao, D., Liu, S., Zhuang, W., Li, L., & Tao, Y. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01442-3 · Cited by 297 · see citing works
“Interestingly, the study found that when the amino acid adequacy is low, a protein subcomplex called GTPaseactivating target of rapamycin 1(GATOR1) has been shown to inactivate the rag heterodimer complex, thereby inhibiting the ability of RAG GTPase heterodimer to recruit mTORC1 on the surface of the enzyme body.(314…”
BackgroundAmino Acid-Dependent mTORC1 Regulation by the Lysosomal Membrane Protein SLC38A9
Jung, J., Genau, H. M., & Behrends, C. (2015) · Molecular and Cellular Biology · doi:10.1128/mcb.00125-15 · Cited by 266 · see citing works
“While the GATOR1 (GAP activity toward Rags) complex exhibits GAP activity toward RagA/B (21), FLCN (folliculin) and its interacting partners, FNIP1 (folliculin-interacting protein 1) and FNIP2, act on RagC/D (20).”
BackgroundInfluentialMcConnell, M. J., Moran, J. V., Abyzov, A., Akbarian, S., Bae, T., Cortes-Ciriano, I., Erwin, J. A., Fasching, L., Flasch, D. A., Freed, D., et al. (2017) · Science · doi:10.1126/science.aal1641 · Cited by 262 · see citing works
“DEPDC5 (109, 110) PI3K-AKT-mTOR Epilepsy with FCD mTORC1”
Chemical Proteomics Identifies Druggable Vulnerabilities in a Genetically Defined Cancer
Bar-Peled, L., Kemper, E. K., Suciu, R. M., Vinogradova, E. V., Backus, K. M., Horning, B. D., Paul, T. A., Ichu, T.-A., Svensson, R. U., Olucha, J., et al. (2017) · Cell · doi:10.1016/j.cell.2017.08.051 · Cited by 262 · see citing works
“Oligonucleotides See Table S5 N/A N/A Recombinant DNA pLKO.1:shGFP (Bar-Peled et al., 2013) N/A pLKO.1:shNRF2_1 Sigma-Aldrich TRCN0000284998 (Continued on next page) e2 Cell 171, 1–14.e1–e12, October 19, 2017 Please cite this article in press as: Bar-Peled et al., Chemical Proteomics Identifies…”
Self-citationGoul, C., Peruzzo, R., & Zoncu, R. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00641-8 · Cited by 269 · see citing works
“The cryo-electron microscopy (cryo-EM) structure of human GATOR1 in complex with the Rag heterodimer shows that as the Arg78-containing loop of NPRL2 is inserted in the nucleotide-binding pocket of RagA, an additional interaction is established between RagC and DEPDC5 (ref.”
BackgroundInfluentialWatch What You (Self-) Eat: Autophagic Mechanisms that Modulate Metabolism
Lahiri, V., Hawkins, W. D., & Klionsky, D. J. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.03.003 · Cited by 286 · see citing works
“, 2016) family proteins, which, in response to cytosolic leucine and arginine, respectively, modulate RRAG activity through the GTPase activating proteins GATOR1 and GATOR2 (Bar-Peled et al., 2013; Panchaud et al., 2013).”
BackgroundRibosomal Protein S6 Phosphorylation: Four Decades of Research.
Meyuhas, O. (2015) · International Review of Cell and Molecular Biology · doi:10.1016/bs.ircmb.2015.07.006 · Cited by 259 · see citing works
“In contrast, the pentameric complex, GATOR1, inhibits the mTORC1 pathway by functioning as a GAP for RagA, whereas the trimeric complex, GATOR2 negatively regulates GATOR1 (Bar-Peled et al., 2013).”
BackgroundEmerging Roles for the Lysosome in Lipid Metabolism
Thelen, A. M., & Zoncu, R. (2017) · Trends in Cell Biology · doi:10.1016/j.tcb.2017.07.006 · Cited by 268 · see citing works
Ricos, M. G., Hodgson, B. L., Pippucci, T., Saidin, A., Ong, Y. S., Heron, S. E., Licchetta, L., Bisulli, F., Bayly, M. A., Hughes, J., et al. (2016) · Annals of Neurology · doi:10.1002/ana.24547 · Cited by 246 · see citing works
“This complex has been shown to act as a GAP (GTPase-activating protein) for the RagA/B GTPases, which control mTORC1 (mammalian target of rapamycin complex 1) activity.(5) mammalian target of rapamycin (mTOR) is a master regulator of cell growth, and deregulation of mTOR signaling has been associated with multiple dis…”
BackgroundMirzaa, G., Campbell, C., Solovieff, N., Goold, C. P., Jansen, L., Menon, S., Timms, A., Conti, V., Biag, J., Adams, C., et al. (2016) · JAMA Neurology · doi:10.1001/jamaneurol.2016.0363 · Cited by 246 · see citing works
Ribierre, T., Deleuze, C., Bacq, A., Baldassari, S., Marsan, E., Chipaux, M., Muraca, G., Roussel, D., Navarro, V., Leguern, E., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci99384 · Cited by 241 · see citing works
Amino Acid Sensing by mTORC1: Intracellular Transporters Mark the Spot
Goberdhan, D., Wilson, C., & Harris, A. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.03.013 · Cited by 240 · see citing works
“For example, components of GATOR1 (Figure 2), which negatively regulates amino acid sensing, act as tumor suppressors (Bar-Peled et al., 2013), and RagC mutations have recently been linked to follicular lymphoma (Okosun”
BackgroundRegulation of autophagy by coordinated action of mTORC1 and protein phosphatase 2A
Wong, P.-M., Feng, Y., Wang, J., Shi, R., & Jiang, X. (2015) · Nature Communications · doi:10.1038/ncomms9048 · Cited by 239 · see citing works
The vacuolar-type H+-ATPase at a glance – more than a proton pump
Maxson, M. E., & Grinstein, S. (2014) · Journal of Cell Science · doi:10.1242/jcs.158550 · Cited by 234 · see citing works
“Components of the mTORC1 pathway – the Ragulator complex (comprising LAMTOR1, LAMTOR2, LAMTOR3, LAMTOR4 and LAMTOR5) and the Ras-related GTP-binding proteins (RRAGA, RRAGB, RRAGC and RRAGD; hereafter referred to as Rag GTPases) – localize to the lysosomal membrane in an inactive form (see poster panel ‘Amino-acid- ind…”
BackgroundInfluentialMolecular regulation of autophagy machinery by mTOR‐dependent and ‐independent pathways
Al‐Bari, M. A. A., & Xu, P. (2020) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14305 · Cited by 265 · see citing works
Translational reprogramming in cellular stress response
Liu, B., & Qian, S. (2013) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1212 · Cited by 249 · see citing works
Quantitative analysis of T cell proteomes and environmental sensors during T cell differentiation
Howden, A. J. M., Hukelmann, J. L., Brenes, A., Spinelli, L., Sinclair, L. V., Lamond, A. I., & Cantrell, D. A. (2019) · Nature Immunology · doi:10.1038/s41590-019-0495-x · Cited by 231 · see citing works
Harpur, B., Kent, C. F., Molodtsova, D., Lebon, J., Alqarni, A., Owayss, A., & Zayed, A. (2014) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1315506111 · Cited by 229 · see citing works
“Vg in turn regulates the central insulin/Tor growth pathway (49) and both of the bee’s insulin receptors and the Depdc5 gene—part of a complex which sensitizes Tor signaling to cellular amino acid levels (50)—are under positive selection.”
BackgroundScheffer, I., Heron, S., Regan, B. M., Mandelstam, S., Crompton, D., Hodgson, B., Licchetta, L., Provini, F., Bisulli, F., Vadlamudi, L., et al. (2014) · Annals of Neurology · doi:10.1002/ana.24126 · Cited by 228 · see citing works
“However, under conditions of amino acid deprivation, GATOR1 inhibits mTORC1 activation by acting as a GTPase activating protein for Rag GTPases.11 Activation of the mTORC1 pathway leads to increased synthesis of proteins and lipids to generate new cell membranes, increased cellular metabolism, and energy production.”
BackgroundInfluentialPeng, M., Yin, N., & Li, M. O. (2014) · Cell · doi:10.1016/j.cell.2014.08.038 · Cited by 220 · see citing works
- 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
- Health Sciences › Medicine › Epidemiology › 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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