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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
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TORC1 regulators Iml1/GATOR1 and GATOR2 control meiotic entry and oocyte development in Drosophila
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“The three proteins described above, Iml1/DEPDC5, Npr2/Nprl2, and Npr3/ Nprl3, form the Iml1/GATOR1 complex and inhibit TORC1 (3, 4).”
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“The Rag GAP of the GATOR complex is reported to be highly selective for RagA/B in vitro (26).”
BackgroundCurrent Approaches and Future Directions for the Treatment of mTORopathies
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“We performed a similar mutation screen with arginine mutants of Nprl3 in Nprl3-knockout cells and found all the mutants we created behave similarly to WT Nprl3 (data not shown).”
BackgroundInfluentialSelf-citationWeak membrane interactions allow Rheb to activate mTORC1 signaling without major lysosome enrichment
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Mitochondrial AKAP1 supports mTOR pathway and tumor growth
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“The nucleotide loading state of the Rag proteins is controlled by the GAP activity of GATOR1/2 proteins.(25) GATOR2 enhancement of mTORC1 is inhibited by its interaction with sestrin2, an evolutionarily-conserved stressinducible protein that suppresses oxidative stress.”
BackgroundIs REDD1 a Metabolic Éminence Grise ?
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“SL C3 8A 9 Rheb Rheb-GDP -GTP Insulin/ growth factors GATOR1 GATOR2 Sestrin2 GATOR2 Amino acid insufficiency Increased amino acid provision Leucyl-tRNA synthetase MAP4K3 Vps34 IPMK RalA GTPase Folliculin (FLCN) GSK3 Sestrin2 V-ATPase GTP GDP RagA/B RagC/D Amino acids + V-ATPase Cytosol + GAP ac vity GEF ac vity ?”
BackgroundInfluentialThe mTOR–lysosome axis at the centre of ageing
Carosi, J. M., Fourrier, C., Bensalem, J., & Sargeant, T. J. (2021) · FEBS Open Bio · doi:10.1002/2211-5463.13347 · Cited by 70
Upstream ORF-Encoded ASDURF Is a Novel Prefoldin-like Subunit of the PAQosome
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“On the other hand, GATOR2 is able to block the GAP activity of GATOR1 [128], thus activating TORC1.”
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Epilepsy Genetics Revolutionizes Clinical Practice
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Sestrin mediates detection of and adaptation to low-leucine diets in Drosophila
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Self-citationLeucine-sensing mechanism of leucyl-tRNA synthetase 1 for mTORC1 activation
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Autophagosome Biogenesis Machinery
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Rag GTPase in amino acid signaling
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“Furthermore, in GATOR1-null cancer cells, mTOR still localized to the lysosomal surface upon amino acid withdrawal and was resistant to amino acid starvation (Bar-Peled et al. 2013).”
InfluentialDutchak, P. A., Estill-Terpack, S. J., Plec, A. A., Zhao, X., Yang, C., Chen, J., Ko, B., Deberardinis, R. J., Yu, Y., & Tu, B. P. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.04.058 · Cited by 53
“for small RAG GTPases to inhibit mTORC1 during amino acid limitation (Bar-Peled et al., 2013; Dutchak et al., 2015; Neklesa and Davis, 2009; Panchaud et al., 2013).”
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“In this configuration, the Rag heterodimer can recruit mTORC1 to the lysosomal surface, where mTORC1 is activated by the small GTPase Rheb (Ras homolog enriched in brain) (Bar-Peled et al. 2013).”
BackgroundRegulation of mTORC1 by the Rag GTPases
Lama-Sherpa, T. D., Jeong, M., & Jewell, J. L. (2023) · Biochemical Society Transactions · doi:10.1042/bst20210038 · Cited by 52
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“GATOR2 constructs were originated from the David Sabatini lab (19) and obtained through Addgene.”
MethodSleep-related hypermotor epilepsy: prevalence, impact and management strategies
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“Some ADSHE families and SHE sporadic cases have been found to have mutations in DEPDC5, and NPRL2 and 3, all encoding proteins of the mTORC1-regulating GATOR1 complex, a key regulator of cell growth.(44,45) The mutations were first identified in patients with familial focal epilepsy with variable foci (FFEVF)(46) and…”
Tian, W.-T., Huang, X.-J., Mao, X., Liu, Q., Liu, X.-L., Zeng, S., Guo, X.-N., Shen, J.-Y., Xu, Y.-Q., Tang, H.-D., et al. (2018) · Movement Disorders · doi:10.1002/mds.27274 · Cited by 52
“The role of DEPDC5 in the development of epileptic foci remains unclear.(39) In our study, whether the different phenotypes within the G E N O T Y P E A N D P H E N O T Y P E O F P R R T 2 - N E G A T I V E P K D”
BackgroundGai, Z., Wang, Q., Yang, C., Wang, L., Deng, W., & Wu, G. (2016) · Cell Discovery · doi:10.1038/celldisc.2016.51 · Cited by 58
Zheng, X., Liang, Y., He, Q., Yao, R., Bao, W., Bao, L., Wang, Y., & Wang, Z. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms151120753 · Cited by 54
“form, which inhibits mTORC1 activation [76–81].”
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“DEPDC5 to inhibit TORC1 activity in response to amino-acid stress.(21,23,24,26) To confirm the association of Nprl2/CG9104 and Nprl3/CG8783 in Drosophila, we coexpressed the Nprl2HA and Nprl3-V5 tagged proteins in S2 cells and found that Nprl2-HA specifically coimmunoprecipitated with Nprl3-V5 (Figure 1a).”
BackgroundMethodInfluentialNewton, P. T., Vuppalapati, K. K., Bouderlique, T., & Chagin, A. (2015) · Autophagy · doi:10.1080/15548627.2015.1068489 · Cited by 51
“However, mutations in genes encoding GATOR1 proteins, makes MTORC1 signaling resistant to a v-ATPase inhibitor, thereby providing a possibility that v-ATPase-dependent MTORC1 regulation might differ in different cellular settings.(28) Interestingly, activation of MTORC1 by CQ in osteoclasts is quite weak (about 2-fold…”
BackgroundRegulation of Muscle Growth in Early Postnatal Life in a Swine Model
Rudar, M., Fiorotto, M. L., & Davis, T. A. (2018) · Annual Review of Animal Biosciences · doi:10.1146/annurev-animal-020518-115130 · Cited by 69
“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript Table 1 Developmental changes in components upstream and downstream of mTORC1 in neonatal pig skeletal muscle Item Effect on protein synthesis Effect of develo…”
BackgroundInfluentialDepdc5 knockdown causes mTOR ‐dependent motor hyperactivity in zebrafish
de Calbiac, H., Nagy-Dăbâcan, A., Marsan, E., Tostivint, H., Devienne, G. F., Ishida, S., Leguern, É., Baulac, S., Muresan, R. C., Kabashi, E., et al. (2018) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.542 · Cited by 59
“DEPDC5 has been described as an essential part of the GATOR1 complex, an inhibitor of mTORC1.(10,12) In accordance with this, treatment of depdc5 knockdown fish with the mTORC1 inhibitor, rapamycin, significantly improved the deviation angle of the swimming trajectory at 72 hpf (54.”
The Role of mTOR in Neuroendocrine Tumors: Future Cornerstone of a Winning Strategy?
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“Interestingly, 2 other samples harbored mutations in the DEPDC5 gene, which encodes for a subunit of the negative regulator of mTORC1 activity, GATOR1 [35].”
BackgroundInfluentialMultifaceted Roles of ALG-2 in Ca2+-Regulated Membrane Trafficking
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Sestrins as a Therapeutic Bridge between ROS and Autophagy in Cancer
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“A crucial determinant of the activation state of Rag small GTPases, of relevance to the focus of this review, is the “GATOR” super-complex, composed of two complexes of opposing function: GATOR1 (containing DEP Domain Containing 5 (DEPDC5), Nprl2 and Nprl3, negatively regulating RagA:B, and considered an important tum…”
The effect of adipocyte–macrophage crosstalk in obesity-related breast cancer
Engin, A. B., Engin, A., & Gönül, İ. I. (2019) · Journal of Molecular Endocrinology · doi:10.1530/jme-18-0252 · Cited by 64
Non-canonical mTOR-Independent Role of DEPDC5 in Regulating GABAergic Network Development
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Post-absorptive muscle protein turnover affects resistance training hypertrophy
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“2012), it might be a regulatory site of protein turnover (Bar-Peled et al. 2013).”
Leucine and Mammalian Target of Rapamycin–Dependent Activation of Muscle Protein Synthesis in Aging
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Role of autophagy in muscle disease
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Indole-3-acetic acid is a physiological inhibitor of TORC1 in yeast
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NLK phosphorylates Raptor to mediate stress-induced mTORC1 inhibitionPreprint
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“The Rag GTPases are activated by amino acids via the Ragulator (Sancak et al. 2010; Bar-Peled et al. 2012) and GATOR1 (Bar-Peled et al. 2013) complex, which function as activator (GEF) and inhibitor (GAP) for Rag GTPases, respectively.”
BackgroundTranslational control by oncogenic signaling pathways
Gao, B., & Roux, P. P. (2014) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2014.11.006 · Cited by 46
NPRL2 enhances autophagy and the resistance to Everolimus in castration‐resistant prostate cancer
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Ghosh, J., & Kapur, R. (2017) · Experimental Hematology · doi:10.1016/j.exphem.2017.02.004 · Cited by 69
“Amino acids facilitate translocation of mTORC1 to the lysosomal surface through Rag heterodimer-dependent and independent pathways (Figure 2) (18-23).”
BackgroundNumrich, J., Gulli, M., Arlt, H., Sardu, A., Griffith, J. M., Levine, T. P., Engelbrecht-Vandré, S., Reggiori, F., VIRGILIO, C. D., & Ungermann, C. (2015) · Journal of Cell Science · doi:10.1242/jcs.164905 · Cited by 57
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Multifaceted activities of transcription factor EB in cancer onset and progression
Astanina, E., Bussolino, F., & Doronzo, G. (2020) · Molecular Oncology · doi:10.1002/1878-0261.12867 · Cited by 50
The Regulatory Role of Key Metabolites in the Control of Cell Signaling
Milanesi, R., Coccetti, P., & Tripodi, F. (2020) · Biomolecules · doi:10.3390/biom10060862 · Cited by 52
Control of mTOR Signaling by Ubiquitin
Jiang, Y., Su, S.-Y., Zhang, Y.-Q., Qian, J.-Y., & Liu, P.-D. (2019) · Oncogene · doi:10.1038/s41388-019-0713-x · Cited by 46
A recurrent mutation in DEPDC5 predisposes to focal epilepsies in the French‐Canadian population
Martin, C., Meloche, C., Rioux, M., Nguyen, D., Carmant, L., Andermann, E., Gravel, M., & Cossette, P. (2014) · Clinical Genetics · doi:10.1111/cge.12311 · Cited by 46
“(12) suggest that the protein could interact with the mTOR pathway, which plays a major role in cell growth.”
BackgroundDistinct amino acid–sensing mTOR pathways regulate skeletal myogenesis
Yoon, M., & Chen, J. (2013) · Molecular Biology of the Cell · doi:10.1091/mbc.e13-06-0353 · Cited by 48
“…Ragulator protein complex and the GTPase-activating protein activity of the GATOR complex, bind raptor and translocate mTORC1 to the lysosomal surface in response to amino acid stimulation, which is necessary for the activation of mTORC1 (Sancak et al., 2008, 2010; Bar-Peled et al., 2012, 2013).”
BackgroundIntegration of signals generated by nutrients, hormones, and exercise in skeletal muscle.
Kimball, S. (2014) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.113.068387 · Cited by 46
“The molecular details through which amino acids act to modulate Ragulator and GATOR regulation of mTORC1 are unclear.”
BackgroundInfluentialLee, W. S., Baldassari, S., Stephenson, S. E. M., Lockhart, P. J., Baulac, S., & Leventer, R. J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031344 · Cited by 45
“DEPDC5 is a component of the GATOR1 complex [36], which functions as a repressor in the amino acid-sensing branch mTOR path-”
BackgroundChen, S.-W., Abou-Khalil, B., Afawi, Z., Ali, Q. Z., Amadori, E., Anderson, A., Anderson, J., Andrade, D. M., Annesi, G., Arslan, M., et al. (2023) · medRxiv · doi:10.1101/2023.02.22.23286310 · Cited by 45
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How the amino acid leucine activates the key cell-growth regulator mTOR
Vellai, T. (2021) · Nature · doi:10.1038/d41586-021-01943-7 · Cited by 52
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“DEPDC5 is a critical component of the GATOR1 complex, a negative regulator of mTORC1 activity (11).”
BackgroundInfluentialWhi2 is a conserved negative regulator of TORC1 in response to low amino acids
Chen, X., Wang, G., Zhang, Y., Dayhoff-Brannigan, M., Diny, N. L., Zhao, M., He, G., Sing, C. N., Metz, K. A., Stolp, Z. D., et al. (2018) · PLoS Genetics · doi:10.1371/journal.pgen.1007592 · Cited by 54
Laxman, S., Sutter, B. M., Shi, L., & Tu, B. P. (2014) · Science Signaling · doi:10.1126/scisignal.2005948 · Cited by 55
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Snf1/AMPK fine-tunes TORC1 signaling in response to glucose starvation
Caligaris, M., Nicastro, R., Hu, Z., Tripodi, F., Hummel, J. E., Pillet, B., Deprez, M.-A., Winderickx, J., Rospert, S., Coccetti, P., et al. (2023) · eLife · doi:10.7554/elife.84319 · Cited by 61
“…protein complexes (i.e. yeast SEACIT/mammalian GATOR1 and yeast Lst4-Lst7/mammalian FNIP-FLCN acting on Gtr1/RagA/B and Gtr2/RagC/D, respectively Bar-Peled et al., 2013 ; Panchaud et al., 2013a ; Panchaud et al., 2013b ; Péli-Gulli et al., 2015 ; Petit et al., 2013 ; Shen et al., 2017 ; Tsun et…”
The role of branched chain amino acids metabolic disorders in tumorigenesis and progression
Wang, J., Wang, W., Zhu, F., & Duan, Q. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113390 · Cited by 47
Pharmacological convergence reveals a lipid pathway that regulates C. elegans lifespan
Chen, A. L., Lum, K. M., Lara-González, P., Ogasawara, D., Cognetta, A. B., To, A., Parsons, W. H., Simon, G. M., Desai, A. B., Petrascheck, M., et al. (2019) · Nature Chemical Biology · doi:10.1038/s41589-019-0243-4 · Cited by 51
Self-citationAmino acids and amino acid sensing: implication for aging and diseases
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“In addition, balloon cells have been shown to be silent electrographically.19 Genetically, germline DEPDC5 mutations occur more often than all other mutations in FE-related genes combined9 and directly inhibit MTOR 144 Volume 84, No. 1 ANNALS of Neurology independently of TSC1/TSC2.”
BackgroundInfluentialMartínez-Noël, G., Luck, K., Kühnle, S., Desbuleux, A., Szajner, P., Galligan, J. T., Rodriguez, D., Zheng, L., Boyland, K. A., Leclere, F., et al. (2018) · Journal of Molecular Biology · doi:10.1016/j.jmb.2018.01.021 · Cited by 53
“Although HERC2 itself does not associate with mTORC1, it associates with the mTORC1 regulatory complex GATOR 2 [59] and with the EIF3 complex, which is necessary for mTORC1 signaling through the translational regulators S6K1 and 4E-BP1 [58].”
BackgroundSpatial Activation of TORC1 Is Regulated by Hedgehog and E2F1 Signaling in the Drosophila Eye
Kim, W., Jang, Y., Yang, J., & Chung, J. (2017) · Developmental Cell · doi:10.1016/j.devcel.2017.07.020 · Cited by 36
Gordon, B. S., Steiner, J. L., Williamson, D. L., Lang, C. H., & Kimball, S. R. (2016) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00059.2016 · Cited by 49
“In contrast, amino acids activate mTORC1 through the concerted action of several guanine nucleotide exchange factors (GEFs) and GAPs that act to modulate the GTP/GDP loading status of the Rag proteins (6, 7, 110).”
BackgroundRegulation of Hematopoiesis and Methionine Homeostasis by mTORC1 Inhibitor NPRL2
Dutchak, P. A., Laxman, S., Estill, S. J., Wang, C., Wang, Y., Wang, Y., Bulut, G. B., Gao, J., Huang, L. J.-S., & Tu, B. P. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.06.042 · Cited by 48
“In response to growth factor or nutrient insufficiency, mTORC1 is inhibited by upstream negative regulators that act on small GTPases that are important for mTORC1 function.”
BackgroundMethodInfluentialPRMT1 orchestrates with SAMTOR to govern mTORC1 methionine sensing via Arg-methylation of NPRL2
Jiang, C., Liu, J., He, S., Xu, W., Huang, R., Pan, W., Li, X., Dai, X., Guo, J., Zhang, T., et al. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.11.001 · Cited by 49
Egri, S. B., Ouch, C., Chou, H., Yu, Z., Song, K., Xu, C., & Shen, K. (2022) · Molecular Cell · doi:10.1016/j.molcel.2022.03.002 · Cited by 53
Molecular mechanisms relating to amino acid regulation of protein synthesis
Cao, Y., Liu, S., Liu, K., Abbasi, I. H. R., Cai, C., & Yao, J. (2019) · Nutrition Research Reviews · doi:10.1017/s0954422419000052 · Cited by 49
“Inhibition of GATOR1 subunits makes mTORC1 signalling resistant to AA deprivation, while inhibition of GATOR2 subunits suppresses mTORC1 signalling(71).”
BackgroundIntestinal apical polarity mediates regulation of TORC1 by glucosylceramide in C. elegansPreprint
Zhu, H., Sewell, A. K., & Han, M. (2015) · Genes & Development · doi:10.1101/gad.263483.115 · Cited by 42
“This function of the worm NPRL-2/3 complex is distinct from the reported role of the NPRL2/3 complex as a GTPase-activating protein to regulate RagA/B in mammalian cell lines and yeast (Bar-Peled et al. 2013; Panchaud et al. 2013).”
BackgroundResultInfluentialKlofas, L. K., Short, B. P., Zhou, C.-W., & Carson, R. P. (2020) · Human Molecular Genetics · doi:10.1093/hmg/ddaa068 · Cited by 42
“The GATOR1 complex acts to inhibit RagA/B-mediated recruitment of mTORC1 to the lysosomal membrane during times of nutrient deprivation, thereby preventing its activation and phosphorylation of downstream targets (12).”
BackgroundMethodDawson, R. E., Guil, A. N. N., Robertson, L., Piltz, S. G., Hughes, J. N., & Thomas, P. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104640 · Cited by 42
“Previous in vitro studies have shown that GATOR1 functions to negatively regulate signalling of the mechanistic target of rapamycin complex 1 (mTORC1) pathway, with knockdown cell lines being insensitive to amino acid starvation, (Bar-Peled et al., 2013; Iffland et al., 2018).”
BackgroundMethodThe lysosomal GPCR-like protein GPR137B regulates Rag and mTORC1 localization and activity
Gan, L., Seki, A., Shen, K., Iyer, H., Han, K., Hayer, A., Wollman, R., Ge, X., Lin, J. R., Dey, G., et al. (2019) · Nature Cell Biology · doi:10.1038/s41556-019-0321-6 · Cited by 53
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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