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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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Cites
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“REAGENT or RESOURCE SOURCE IDENTIFIER CUY11973: MATa; his3D1, leu2D0, met15D0, ura3D0 fab1S202A/S203A/S204A/T206A/S208A/S210A::mNeonGreen:: hphNT1 IVY1::3xmcherry-ClonNAT This study N/A CUY11974: MATa; his3D1, leu2D0, met15D0, ura3D0 fab1S202D/S203D/S204D/T206D/S208D/S210D::mNeonGreen:: hphNT1 IVY1::3xmcherry-ClonNAT…”
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“Low-frequency inactivating mutations in subunits of the GATOR1 complex have been identified in glioblastoma and ovarian cancers, and cell lines with these mutations display elevated mTORC1 signaling that is insensitive to amino acid depletion (Bar-Peled et al. 2013).”
BackgroundDEPDC5 as a potential therapeutic target for epilepsy
Myers, K. A., & Scheffer, I. E. (2017) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2017.1316715 · Cited by 50
“Loss of GATOR1 impairs inactivation of mechanistic (formerly mammalian) target of rapamycin (mTOR) complex 1 (mTORC1) [1].”
BackgroundWang, S., Schianchi, F., Neumann, D., Wong, L.-Y., Sun, A., van Nieuwenhoven, F. A., Zeegers, M. P., Strzelecka‐Kiliszek, A., Cöl, Ü., Glatz, J. F. C., et al. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101293 · Cited by 59
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BackgroundGeorgescu, M., Islam, M. Z., Li, Y., Traylor, J., & Nanda, A. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01170-1 · Cited by 39
“W905*, an mTOR inhibitor [23], and several nuclear DNA effectors.”
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Kitada, M., Xu, J., Ogura, Y., Monno, I., & Koya, D. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00715 · Cited by 40
“In contrast, GATOR2 is a complex consisting of five proteins, Sec13, Seh1L, WDR24, WDR59, and Mios (Bar-Peled et al., 2013).”
BackgroundStructural Insights into TOR Signaling
Tafur, L., Kefauver, J. M., & Loewith, R. (2020) · Genes · doi:10.3390/genes11080885 · Cited by 42
“The lysosome-associated complex KICSTOR interacts with GATOR1 to recruit it to the lysosome in response to nutritional cues [63], while the GATOR2 complex appears to antagonize the GAP activity of GATOR1 in an unknown way [64].”
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Tsai, M.-H., Chan, C.-K., Chang, Y., Yu, Y.-T., Chuang, S., Fan, W., Li, S.-C., Fu, T.-Y., Chang, W.-N., Liou, C., et al. (2017) · Clinical Genetics · doi:10.1111/cge.12992 · Cited by 39
“Mutations in the disheveled, Egl-10 and pleckstrin domain-containing protein 5 (DEPDC5) gene have recently been identified to be an important cause of familial focal epilepsy with variable foci (FFEVF),1,2 autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE, recently renamed as autosomal dominant sleep-related…”
BackgroundSensing the Environment Through Sestrins: Implications for Cellular Metabolism
Parmigiani, A., & Budanov, A. V. (2016) · International review of cytology · doi:10.1016/bs.ircmb.2016.05.003 · Cited by 40
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Disruption of the Rag-Ragulator Complex by c17orf59 Inhibits mTORC1
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“Seh1L is also a component of the nuclear pore complex, where it binds directly to Sec13 (Brohawn et al., 2009).”
InfluentialSelf-citationTargeting tissue-specific metabolic signaling pathways in aging: the promise and limitations
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“Inhibition of GATOR1 leads to mTORC1 activation while inhibition of GATOR2 results in mTORC1 inactivation (Bar-Peled et al., 2013).”
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“The GATOR subcomplex acts as a GTPase-activator protein for Rags A/B, thereby opposing the function of Ragulator.”
BackgroundInfluentialAn update on the bridging factors connecting autophagy and Nrf2 antioxidant pathway
Ning, B., Hang, S., Zhang, W., Mao, C., & Li, D. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1232241 · Cited by 43
“GATOR1 inhibits mTORC1 signaling, while GATOR2 positively regulates mTORC1 and inhibits GATOR1 by forming a complex at the lysosomal membrane (Bar-Peled et al., 2013).”
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“It has been suggested that GATOR1 displays GAP activity toward RagA/B and functions as a negative regulator of mTORC1 signaling, whereas GATOR2 acts as an endogenous inhibitor to GATOR1 activity [7,60].”
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Lysosomes at the Crossroads of Cell Metabolism, Cell Cycle, and Stemness
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“4A), which is consistent with reports that suggest that DEPDC5 is a negative regulator of the mTORC1 signaling pathway as a component of the GATOR1 complex (22).”
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“…the Sabatini group identified the GATOR1 complex as a GTPase-activating protein (GAP) for the RagA/B GTPases, and as a major negative regulator of the amino acid sensing pathway, loss of which causes mTORC1 signalling to be completely insensitive to amino acid deprivation (Bar-Peled et al., 2013).”
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“Mechanistically, recent observations by BarPeled et al [42] revealed that inactivating mutations in the DEPDC5 subunit of the GATOR1-mTOR inhibitory complex conferred mTOR hyperactivation and marked gain in sensitivity to rapamycin.”
BackgroundGenetics advances in autosomal dominant focal epilepsies: focus on DEPDC5.
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CDK5-PRMT1-WDR24 signaling cascade promotes mTORC1 signaling and tumor growth
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InfluentialAction Mechanism of Metformin and Its Application in Hematological Malignancy Treatments: A Review
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BackgroundStructure of the TSC2 GAP Domain: Mechanistic Insight into Catalysis and Pathogenic Mutations
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Garrido, N. D. M., & Aylett, C. H. S. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00108 · Cited by 37
“Conversely, when amino acid levels are low, the opposite Rag GTPase nucleotide binding state, in which RagA/B is GDP-bound and RagC/D is GTP-bound, is favored, which results in the release of mTORC1 from the lysosome.”
BackgroundInfluentialIffland, P. H., Baybis, M., Barnes, A. E., Leventer, R., Lockhart, P., & Crino, P. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.02.013 · Cited by 33
Recycling the danger via lipid droplet biogenesis after autophagy
Li, Y., Zong, W.-X., & Ding, W.-X. (2017) · Autophagy · doi:10.1080/15548627.2017.1371394 · Cited by 33
TSC2 mediates hyperosmotic stress-induced inactivation of mTORC1
Plescher, M., Teleman, A. A., & Demetriades, C. (2015) · Scientific Reports · doi:10.1038/srep13828 · Cited by 36
Branched‐Chain Amino Acid Accumulation Fuels the Senescence‐Associated Secretory Phenotype
Liang, Y., Pan, C. C., Yin, T., Wang, L., Gao, X., Wang, E., Quang, H., Huang, D., Tan, L., Xiang, K., et al. (2023) · Advanced Science · doi:10.1002/advs.202303489 · Cited by 35
Cryo-EM structure of the SEA complex
Tafur, L., Hinterndorfer, K., Gabus, C., Lamanna, C., Bergmann, A., Sadian, Y., Hamdi, F., Kyrilis, F., Kastritis, P., & Loewith, R. (2022) · Nature · doi:10.1038/s41586-022-05370-0 · Cited by 32
Desai, H. S., Yan, T., Yu, F., Sun, A. W., Villanueva, M., Nesvizhskii, A. I., & Backus, K. M. (2022) · Molecular & Cellular Proteomics · doi:10.1016/j.mcpro.2022.100218 · Cited by 37
The Roles of Post-Translational Modifications on mTOR Signaling
Yin, S., Liu, L., & Gan, W. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041784 · Cited by 39
Liu, L., Chen, Z.-R., Xu, H., Liu, D.-T., Mao, Y., Liu, H.-K., Liu, X.-R., Zhou, P., Lin, S.-M., Li, B., et al. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00821 · Cited by 32
“Previous studies have showed that DEPDC5 mutations are associated with diverse focal epileptic phenotypes, ranging from mild rolandic epilepsy to severe MCD-associated epilepsies (Baulac, 2016).”
BackgroundNutrient Control of mRNA Translation
Shu, X. E., Swanda, R. V., & Qian, S. (2020) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-120919-041411 · Cited by 39
“The Ragulator complex acts as a guanine nucleotide exchange factor (GEF) toward RagA and RagB, whereas another complex called GATOR1 has GAP activity (9, 10).”
BackgroundBurger, B. J., Rose, S., Bennuri, S. C., Gill, P. S., Tippett, M., Delhey, L. M., Melnyk, S., & Frye, R. E. (2017) · Frontiers in Pediatrics · doi:10.3389/fped.2017.00219 · Cited by 39
“Inactivating mutations in GATOR1, such as DEPDC5, result in mTORC1 being hyperactive, insensitive to amino acid starvation, and hypersensitive to rapamycin (65).”
BackgroundWei, Y., Reveal, B., Cai, W., & Lilly, M. A. (2016) · G3 Genes|Genomes|Genetics · doi:10.1534/g3.116.035337 · Cited by 31
“In contrast, in mammalian and Drosophila tissue culture cells, depleting GATOR1 components results in a dramatic increase in TORC1 activity under standard culture conditions (Bar-Peled et al. 2013; Wei and Lilly 2014).”
Kim, K., Yoo, H. C., Kim, B., Kim, S., Sung, Y., Yoon, I., Yu, Y. C., Park, S. J., Kim, J. H., Myung, K., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-30696-8 · Cited by 31
Liu, Z., Yan, M., Lei, W., Jiang, R., Dai, W., Chen, J., Wang, C., Li, L., Wu, M., Nian, X., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci155096 · Cited by 34
Lysosomes in acute myeloid leukemia: potential therapeutic targets?
Rafiq, S., McKenna, S. L., Muller, S., Tschan, M. P., & Humbert, M. (2021) · Leukemia · doi:10.1038/s41375-021-01388-x · Cited by 34
“A key integrator of amino acid signaling is the GTPase-activating proteins toward Rags (GATOR) complex [22].”
BackgroundThe regulation of healthspan and lifespan by dietary amino acids
Babygirija, R., & Lamming, D. W. (2021) · Translational Medicine of Aging · doi:10.1016/j.tma.2021.05.001 · Cited by 43
Cytoskeletal vimentin regulates cell size and autophagy through mTORC1 signaling
Mohanasundaram, P., Coelho‐Rato, L. S., Modi, M. K., Urbanska, M., Lautenschläger, F., Cheng, F., & Eriksson, J. (2022) · PLoS Biology · doi:10.1371/journal.pbio.3001737 · Cited by 34
Olaniyan, E. T., O’Halloran, F., & McCarthy, A. L. (2020) · Nutrition Research Reviews · doi:10.1017/s0954422420000219 · Cited by 39
“Src regulatesmTORC1 activity via Rag GTPases(30), by causing the separation of Gap Activity TOward Rags 1 (GATOR1), a Rag GTPase-activating protein, from the Rag proteins(29).”
BackgroundInfluentialGenetic characterization identifies bottom-of-sulcus dysplasia as an mTORopathy
Lee, W., Stephenson, S. E. M., Pope, K., Gillies, G., Maixner, W., Macdonald-Laurs, E., MacGregor, D., D'Arcy, C., Jackson, G., Harvey, A., et al. (2020) · Neurology · doi:10.1212/wnl.0000000000010670 · Cited by 31
Rapid acting antidepressants in the mTOR pathway: Current evidence
Athira, K. V., Mohan, A. S., & Chakravarty, S. (2020) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2020.07.022 · Cited by 34
RagC phosphorylation autoregulates mTOR complex 1
Yang, G., Humphrey, S. J., Murashige, D., Francis, D., Wang, Q., Cooke, K. C., Neely, G. G., & James, D. E. (2018) · The EMBO Journal · doi:10.15252/embj.201899548 · Cited by 35
“These include the Ragulator (GEF for Rag A/B; Bar-Peled et al , 2012), the GATOR1 complex (GAP for RagA/B; Bar-Peled et al , 2013), folliculin (FLCN, GAP for RagC/D; Petit et al , 2013; Tsun et al , 2013), and leucyl-tRNA synthetase (LeuRS, GAP for RagD; Han et al , 2012).”
Patursky-Polischuk, I., Kasir, J., Miloslavski, R., Hayouka, Z., Hausner-Hanochi, M., Stolovich-Rain, M., Tsukerman, P., Biton, M., Mudhasani, R., Jones, S. N., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0109410 · Cited by 28
“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 [24].”
BackgroundValenstein, M. L., Lalgudi, P. V., Gu, X., Kedir, J. F., Taylor, M. S., Chivukula, R. R., & Sabatini, D. M. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2322755121 · Cited by 34
Self-citationThe rapid proximity labeling system PhastID identifies ATP6AP1 as an unconventional GEF for Rheb
Feng, R., Liu, F., Li, R., Zhou, Z., Lin, Z., Song, L., Deng, S., Li, Y., Nong, B., Xia, Y., et al. (2024) · Cell Research · doi:10.1038/s41422-024-00938-z · Cited by 34
Growth or death? Control of cell destiny by mTOR and autophagy pathways
Khalil, M. I. M., Ali, M. M., Holail, J., & Houssein, M. (2023) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2023.10.002 · Cited by 32
Therapeutic modulation of JAK-STAT, mTOR, and PPAR-γ signaling in neurological dysfunctions
Kumar, S., Mehan, S., & Narula, A. S. (2022) · Journal of Molecular Medicine · doi:10.1007/s00109-022-02272-6 · Cited by 33
Amino acid and small GTPase regulation of mTORC1
Nguyen, T. P., Frank, A. R., & Jewell, J. L. (2017) · Cellular Logistics · doi:10.1080/21592799.2017.1378794 · Cited by 37
“Using RagB as bait, IP-MS studies have also identifed the GAP for the RagA/B GTPases.46 The RagA/B GAP is not a single protein, but instead is a multiprotein complex known as GAP activity toward Rags 1 (GATOR1), which is composed of DEP domain containing 5 (DEPDC5), nitrogen permease regulator 2-like protein (NPRL2),…”
BackgroundInfluentialvan Kranenburg, M., Hoogeveen-Westerveld, M., & Nellist, M. (2015) · Human Mutation · doi:10.1002/humu.22723 · Cited by 30
“Here, we employ an analogous approach to assess the effects of DEPDC5 variants identified in individuals with focal epilepsy and in serous ovarian tumors [Cancer Genome Atlas Research Network, 2011; Bar-Peled et al., 2013].”
BackgroundMethodInfluentialTargeting mTOR signaling pathways in multiple myeloma: biology and implication for therapy
Wang, Y., Vandewalle, N., Veirman, K. D., Vanderkerken, K., Menu, E., & Bruyne, E. D. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-024-01699-3 · Cited by 33
“This process recruits mTORC1 to the lysosomal membranes, where Rheb is present, and stimulates mTORC1 activation [50, 51].”
BackgroundDEPDC5 protects CD8+ T cells from ferroptosis by limiting mTORC1-mediated purine catabolism
Li, S., Ouyang, X., Sun, H., Jin, J., Chen, Y., Li, L., Wang, Q., He, Y., Wang, J., Chen, T., et al. (2024) · Cell Discovery · doi:10.1038/s41421-024-00682-z · Cited by 28
mTORC1 in energy expenditure: consequences for obesity
Allard, C., Miralpeix, C., López-Gambero, A. J., & Cota, D. (2024) · Nature Reviews Endocrinology · doi:10.1038/s41574-023-00934-0 · Cited by 39
“Amino acid deprivation activates the GTPase-activating proteins towards the Rags 1 (GATOR1) complex to inhibit RAG GTPases, thereby reducing mTORC1 signalling 15 .”
Lysine crotonylation regulates leucine-deprivation-induced autophagy by a 14-3-3ε-PPM1B axis.
Zheng, Z., Yan, G., Li, X., Fei, Y.-K., Sun, L.-L., Yu, H.-N., Niu, Y.-R., Gao, W.-H., Zhong, Q., & Yan, X.-H. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111850 · Cited by 29
Lei, Y., Huang, Y. J., Wen, X., Yin, Z., Zhang, Z., & Klionsky, D. J. (2022) · Antioxidants · doi:10.3390/antiox11020304 · Cited by 36
“In addition, amino acids inhibit the GATOR1 complex (analogous to yeast SEACIT), the GAP for RRAGA/B, therefore facilitating the activation of the RRAG GTPase [94].”
BackgroundInfluentialArfGAP1 inhibits mTORC1 lysosomal localization and activation
Meng, D., Yang, Q., Melick, C. H., Park, B. C., Hsieh, T., Curukovic, A., Jeong, M., Zhang, J., James, N. G., & Jewell, J. L. (2021) · The EMBO Journal · doi:10.15252/embj.2020106412 · Cited by 36
“A pentameric complex called the Ragulator and the amino acid transporter solute carrier family 38 member 9 (SLC38A9) have been shown to act as GEFs for RagA or RagB (Sancak et al, 2008; Sancak et al, 2010; Bar-Peled et al, 2012).”
InfluentialCai, Y., Xu, G., Wu, F. H., Michelini, F., Chan, C., Qu, X., Selenica, P., Ladewig, E., Castel, P., Cheng, Y., et al. (2021) · Cancer Research · doi:10.1158/0008-5472.can-20-3232 · Cited by 38
“Consistent with a previous study (26), we found that loss of GATOR1 complex upon DEPDC5 KO resulted in high level of mTORC1 signaling irrespective of nutrient status in ERþ breast cancer cell lines, suggesting that DEPDC5 loss leads to the increase of active form of RagA/B, thereby leading to constitutive activation o…”
BackgroundResultInfluentialYang, S., Zhang, Y., Ting, C.-Y., Bettedi, L., Kim, K., Ghaniam, E., & Lilly, M. A. (2020) · Developmental Cell · doi:10.1016/j.devcel.2020.08.006 · Cited by 36
“We observed that under fed conditions, mTOR is largely colocalized with LAMP1 in WT HeLa cells while in WDR24-KO cells mTOR is diffusely localized in the cytosol (Bar-Peled et al., 2013) (Figure 1E).”
BackgroundInfluentialAcute knockdown of Depdc5 leads to synaptic defects in mTOR-related epileptogenesis
Fusco, A. D., Cerullo, M. S., Marte, A., Michetti, C., Romei, A., Castroflorio, E., Baulac, S., & Benfenati, F. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104822 · Cited by 40
Clinical Letter: A case report of targeted therapy with sirolimus for NPRL3 epilepsy.
Vawter-Lee, M., Franz, D., Fuller, C., & Greiner, H. (2019) · Seizure · doi:10.1016/j.seizure.2019.10.007 · Cited by 29
Myeloid folliculin balances mTOR activation to maintain innate immunity homeostasis
Li, J., Wada, S., Weaver, L. K., Biswas, C., Behrens, E. M., & Arany, Z. P. (2019) · JCI Insight · doi:10.1172/jci.insight.126939 · Cited by 30
Le, Y.-C., Zhang, S., Ni, J.-H., You, Y., Luo, K., Yu, Y.-Q., & Shen, X. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-0719-2 · Cited by 29
Roles of autophagy and metabolism in pancreatic cancer cell adaptation to environmental challenges
Maertin, S., Elperin, J. M., Lotshaw, E. M., Sendler, M., Speakman, S., Takakura, K., Reicher, B., Mareninova, O. A., Grippo, P. J., Mayerle, J. V., et al. (2017) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00138.2017 · Cited by 31
“Defects in mTOR nutrient sensing were reported in various cancers (4, 17).”
BackgroundKimball, S. R., Ravi, S., Gordon, B. S., Dennis, M. D., & Jefferson, L. S. (2015) · Journal of Nutrition · doi:10.3945/jn.115.215491 · Cited by 27
Galanin pathogenic mutations in temporal lobe epilepsy.
Guipponi, M., Chentouf, A., Webling, K. E. B., Freimann, K., Crespel, A., Nobile, C., Lemke, J., Hansen, J., Dorn, T., Lesca, G., et al. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv060 · Cited by 29
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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