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Sestrin2 is a leucine sensor for the mTORC1 pathway
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From sensing leucine to metabolic control: The mTORC1 protein kinase complex plays central roles in regulating cell growth and metabolism and is implicated in common human diseases such as diabetes and cancer. The level of the amino acid leucine tells an organism a lot about its physiological state, including how much food is available, how much insulin is going to be needed, and whether new muscle mass can be made (see the Perspective by Buel and Blenis). Wolfson et al. identified a biochemical sensor of leucine, Sestrin2, which connects the concentration of leucine to the control of organismal metabolism and growth. When leucine bound to Sestrin2, it was released from a complex with the mTORC1 regulatory factor GATOR2, activating the mTORC1 complex. Saxton et al. describe the crystal structure of Sestrin2 and show how it specifically detects leucine. Aylett et al. determined the structure of human mTORC1 by cryoelectron microscopy and the crystal structure of a regulatory subunit, Raptor. The results reveal the structural basis for the function and intricate regulation of this important enzyme, which is also a strategic drug target. Science , this issue p. 43 , p. 48 , p. 53 ; see also p. 25
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“Specifically, the Sestrin family of proteins binds to and inhibits the action of GATOR2 when leucine levels are low, permitting GATOR1 to inhibit the recruitment of mTORC1 to the lysosome. Binding of leucine by the Sestrins, particularly Sestrin 2, relieves this inhibition of GATOR2, resulting in the inhibition of GATOR1 GAP activity, and allowing mTORC1 to be recruited to the lysosome 162,169.”
From Targeting the biology of aging with mTOR inhibitors (2023) · cites this paper as [169]
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“Specifically, the Sestrin family of proteins binds to and inhibits the action of GATOR2 when leucine levels are low, permitting GATOR1 to inhibit the recruitment of mTORC1 to the lysosome. Binding of leucine by the Sestrins, particularly Sestrin 2, relieves this inhibition of GATOR2, resulting in the inhibition of GATOR1 GAP activity, and allowing mTORC1 to be recruited to the lysosome 162,169.”
From Targeting the biology of aging with mTOR inhibitors (2023) · cites this paper as [169]
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“and by leucine, which binds to the leucine sensors sestrin 1/2 [174, 175]”
From Effects of Skeletal Muscle Hypertrophy on Fat Mass and Glucose Homeostasis in Humans and Animals: A Narrative Review with Systematic Literature Search (2025) · cites this paper as [174]
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Boussif, O., Lezoualc’h, F., Zanta, M. A., Djavaheri‐Mergny, M., Scherman, D., DEMENEIX, B. A., & Behr, J. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.16.7297 · Cited by 6,256
Kim, D., Sarbassov, D. D., Ali, S. M., King, J. E., Latek, R. R., Erdjument‐Bromage, H., Tempst, P., & Sabatini, D. M. (2002) · Cell · doi:10.1016/s0092-8674(02)00808-5 · Cited by 3,051
Self-citationThe Rag GTPases Bind Raptor and Mediate Amino Acid Signaling to mTORC1
Sancak, Y., Peterson, T. R., Shaul, Y. D., Lindquist, R. A., Thoreen, C. C., Bar-Peled, L., & Sabatini, D. M. (2008) · Science · doi:10.1126/science.1157535 · Cited by 2,773
Self-citationSancak, 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 · cited 5×
“Ragulator anchors the Rag heterodimers to the lysosome and has nucleotide exchange activity for RagA and RagB (21, 25).”
BackgroundInfluentialSelf-citationThe Effect of Retarded Growth Upon the Length of Life Span and Upon the Ultimate Body Size
McCay, C. M., Crowell, M. F., & Maynard, L. A. (1935) · The Journal of Nutrition · doi:10.1093/jn/10.1.63 · Cited by 2,264
Zoncu, R., Bar-Peled, L., Efeyan, A., Wang, S., Sancak, Y., & Sabatini, D. M. (2011) · Science · doi:10.1126/science.1207056 · Cited by 1,673
Self-citationHara, K., Yonezawa, K., Weng, Q.-P., Kozlowski, M. T., BELHAM, C. M., & Avruch, J. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.23.14484 · Cited by 1,370
p53 Target Genes Sestrin1 and Sestrin2 Connect Genotoxic Stress and mTOR Signaling
Budanov, A. V., & Karin, M. (2008) · Cell · doi:10.1016/j.cell.2008.06.028 · Cited by 1,326
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. (2013) · Science · doi:10.1126/science.1232044 · Cited by 1,080 · cited 7×
“Ragulator anchors the Rag heterodimers to the lysosome and has nucleotide exchange activity for RagA and RagB (21, 25).”
BackgroundInfluentialSelf-citationBranched-Chain Amino Acid Metabolism
Harper, A. E., Miller, R. H., & Block, K. P. (1984) · Annual Review of Nutrition · doi:10.1146/annurev.nu.04.070184.002205 · Cited by 1,011
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Branched‐Chain Amino Acids and Mitochondrial Biogenesis: An Overview and Mechanistic Summary
Hinkle, J. S., Rivera, C. N., & Vaughan, R. A. (2022) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.202200109 · Cited by 31
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
Chiu, M., Taurino, G., Bianchi, M. G., Ottaviani, L., Andreoli, R., Ciociola, T., Lagrasta, C. A. M., Tardito, S., & Bussolati, O. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19041099 · Cited by 31
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
Vernizzi, L., Paiardi, C., Licata, G., Vitali, T., Santarelli, S., Raneli, M., Manelli, V., Rizzetto, M., Gioria, M., Pasini, M. E., et al. (2020) · Cells · doi:10.3390/cells9010196 · Cited by 31
Ma, Q., Hu, S., Bannai, M., & Wu, G. (2018) · Amino Acids · doi:10.1007/s00726-018-2541-7 · Cited by 30
Jin, H. R., Du, C. H., Wang, C., Yuan, C., & Du, W. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1548-7 · Cited by 30
Zhang, B. K., Moran, A. M., Bailey, C. G., Rasko, J. E. J., Holst, J., & Wang, Q. (2019) · Cell Communication and Signaling · doi:10.1186/s12964-019-0400-0 · Cited by 32
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Abrams, M. J., Tan, F. H., Li, Y., Basinger, T., Heithe, M. L., Sarma, A., Lee, I. T., Condiotte, Z. J., Raffiee, M., Dabiri, J. O., et al. (2021) · eLife · doi:10.7554/elife.65092 · Cited by 28
Ambrosio, S., Ballabio, A., & Majello, B. (2018) · Autophagy · doi:10.1080/15548627.2018.1520546 · Cited by 30
Suryawan, A., Rudar, M., Fiorotto, M. L., & Davis, T. A. (2020) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00332.2019 · Cited by 31
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Chen, C., Naveed, H., & Chen, K. (2023) · Frontiers in Genetics · doi:10.3389/fgene.2023.1233669 · Cited by 29
Sestrin-3 modulation is essential for therapeutic efficacy of cucurbitacin B in lung cancer cells
Khan, N., Jajeh, F., Khan, M. I., Mukhtar, E., Shabana, S. M., & Mukhtar, H. (2016) · Carcinogenesis · doi:10.1093/carcin/bgw124 · Cited by 29
Sato, Y., Sato, Y., Obeng, K. A., & Yoshizawa, F. (2018) · Nutrition Research · doi:10.1016/j.nutres.2018.05.006 · Cited by 31
Shih, Y., Huang, T., Hu, H., Yen, T., & Hsueh, Y. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107835 · Cited by 26
Pszczolkowski, V. L., & Apelo, S. I. A. (2020) · Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · doi:10.1186/s40104-020-00514-6 · Cited by 33
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Ali, M. Z., Bukhari, S. A., Ali, M. Z., & Lee, H.-W. (2017) · BMB Reports · doi:10.5483/bmbrep.2017.50.12.206 · Cited by 30
Yan, H., Liu, Y., Li, X., Yu, B., He, J., Mao, X., Yu, J., Huang, Z., Luo, Y., Luo, J., et al. (2023) · eLife · doi:10.7554/elife.89750 · Cited by 31
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Deane, C. S., Cox, J., & Atherton, P. J. (2024) · Frontiers in Nutrition · doi:10.3389/fnut.2024.1419229 · Cited by 36
Kao, M., Columbus, D. A., Suryawan, A., Steinhoff‐Wagner, J., Hernandez‐Garcia, A., Nguyen, H. V., Fiorotto, M. L., & Davis, T. A. (2016) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00520.2015 · Cited by 30
Shimkus, K. L., Jefferson, L. S., Gordon, B. S., & Kimball, S. R. (2018) · Physiological Reports · doi:10.14814/phy2.13891 · Cited by 28
Hannaian, S. J., Hodson, N. W., Sawan, S. A., Mazzulla, M., Kato, H., Matsunaga, K., Waskiw‐Ford, M., Duncan, J., Kumbhare, D. A., & Moore, D. R. (2020) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00241.2020 · Cited by 25
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Yoon, M. (2020) · International Journal of Nanomedicine · doi:10.2147/ijn.s254574 · Cited by 35
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Rai, N., & Dey, S. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101186 · Cited by 28
Venkateswaran, G., & Dedhar, S. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.602668 · Cited by 28
Arregui, C. D. L. C., Plata-Gómez, A. B., Deleyto-Seldas, N., García, F., Ortega-Molina, A., Abril-Garrido, J., Rodriguez, E., Nemazanyy, I., Tribouillard, L., Martino, A. D., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23857-8 · Cited by 31
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Zhou, J., Chen, H., Du, J., Tai, H., Han, X., Huang, N., Wang, X., Gong, H., Yang, M., & Xiao, H. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.924081 · Cited by 29
Alam, I., Zhang, H., Du, H., Rehman, N. U., Manghwar, H., Xiao, L., Khan, Z., Batool, K., & Ge, L. (2023) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.2c08051 · Cited by 28
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Lim, C., Janssen, T. A. H., Currier, B. S., Paramanantharajah, N., McKendry, J., Sawan, S. A., & Phillips, S. M. (2024) · Current Developments in Nutrition · doi:10.1016/j.cdnut.2024.103769 · Cited by 31
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Yao, H., Jiang, W., Liao, X., Wang, D., & Zhu, H. (2024) · Life Sciences · doi:10.1016/j.lfs.2024.122803 · Cited by 29
Marcucci, F., & Rumio, C. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00714 · Cited by 27
Eichner, R., Fernández‐Sáiz, V., Targosz, B., & Bassermann, F. C. (2018) · International review of cytology · doi:10.1016/bs.ircmb.2018.06.001 · Cited by 27
Ding, B., Haidurov, A., Chawla, A. T., Parmigiani, A., van de Kamp, G., Dalina, A. A., Yuan, F., Lee, J. H., Chumakov, P. M., Grossman, S. R., et al. (2019) · Oncotarget · doi:10.18632/oncotarget.27367 · Cited by 27
Yao, Y., Hong, S., Ikeda, T., Mori, H., MacDougald, O. A., Nada, S., Okada, M., & Inoki, K. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.10.004 · Cited by 28
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Kaya, A., Phua, C. Z. J., Lee, M. B., Wang, L., Tyshkovskiy, A., Ma, S., Barré, B. P., Liu, W., Harrison, B. R., Zhao, X., et al. (2021) · eLife · doi:10.7554/elife.64860 · Cited by 23
Xie, Z., Zhang, W., & Zhang, Y. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110407 · Cited by 30
Li, N., Li, J., Wang, H., Liu, J., Li, W., Yang, K., Huo, X., Leng, J., Yu, Z., Hu, G., et al. (2022) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgac141 · Cited by 28
Doestzada, M., Zhernakova, D. V., van den Munckhof, I., Wang, D., Kurilshikov, A., Chen, L., Bloks, V. W., van Faassen, M. H. J. R., Rutten, J. H. W., Joosten, L. A. B., et al. (2022) · BMC Medicine · doi:10.1186/s12916-022-02688-4 · Cited by 28
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Ishikawa, T., Kitaura, Y., Kadota, Y., Morishita, Y., Ota, M., Yamanaka, F., Xu, M., Ikawa, M., Inoue, N., Kawano, F., et al. (2017) · Scientific Reports · doi:10.1038/srep39825 · Cited by 26
Al-Baghdadi, R. J. T., Nikonorova, I. A., Mirek, E. T., Wang, Y., Park, J., Belden, W. J., Wek, R. C., & Anthony, T. G. (2017) · Scientific Reports · doi:10.1038/s41598-017-01041-7 · Cited by 27
Sano, A., Kakazu, E., Morosawa, T., Inoue, J., Kogure, T., Ninomiya, M., Iwata, T., Umetsu, T., Nakamura, T., Takai, S., et al. (2018) · Journal of Gastroenterology · doi:10.1007/s00535-018-1435-5 · Cited by 26
Wang, D., He, H. X., & Wei, C. (2022) · Environmental Microbiology · doi:10.1111/1462-2920.16310 · Cited by 33
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Kakazu, E., Sano, A., Morosawa, T., Inoue, J., Ninomiya, M., Iwata, T., Nakamura, T., Takai, S., Sawada, S., Katagiri, H., et al. (2019) · Hepatology Research · doi:10.1111/hepr.13346 · Cited by 26
Rudar, M., Naberhuis, J., Suryawan, A., Nguyen, H. V., Stoll, B., Style, C. C., Verla, M. A., Olutoye, O. O., Burrin, D. G., Fiorotto, M. L., et al. (2021) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00203.2020 · Cited by 25
Yuskaitis, C. J., Modasia, J. B., Schrötter, S., Rossitto, L.-A. M., Groff, K. J., Morici, C., Mithal, D. S., Chakrabarty, R. P., Chandel, N. S., Manning, B. D., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111278 · Cited by 29
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Self-citationKissing, S., Rudnik, S., Daμμe, M., Lüllmann‐Rauch, R., Ichihara, A., Kornak, U., Eskelinen, E., Jabs, S., Heeren, J., Brabander, J. K. D., et al. (2017) · Autophagy · doi:10.1080/15548627.2017.1280216 · Cited by 27
Sutton, M. N., Huang, G. Y., Zhou, J., Mao, W., Langley, R. R., Lü, Z., & Bast, R. C. (2019) · Cancers · doi:10.3390/cancers11050603 · Cited by 25
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Zhang, Y., Zhou, Q., Yang, R., Hu, C., Huang, Z., Zheng, C., Liang, Q., Gong, R., Zhu, X., Gong, H., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-67010-9 · Cited by 25
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Jang, S., Hong, S.-E., Lee, D.-H., Kim, J.-Y., Kim, J. Y., Ye, S.-K., Hong, J., Park, I., & Jin, H. (2021) · BMC Cancer · doi:10.1186/s12885-021-08346-x · Cited by 29
Lin, S., Miao, Y., Zheng, X., Dong, Y., Yang, Q., Yang, Q., Du, S., Xu, J., Zhou, S., & Yuan, T. (2022) · Cell Death Discovery · doi:10.1038/s41420-022-01029-x · Cited by 24
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Otsubo, Y., Matsuo, T., Nishimura, A., Yamamoto, M. P., & Yamashita, A. (2018) · EMBO Reports · doi:10.15252/embr.201744867 · Cited by 24
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Gao, Y., Feng, C., Ma, J., & Yan, Q. (2024) · Biochemical Pharmacology · doi:10.1016/j.bcp.2024.116048 · Cited by 26
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Darawshi, O., Yassin, O., Shmuel, M., Wek, R. C., Mahdizadeh, S. J., Eriksson, L. A., Hatzoglou, M., & Tirosh, B. (2024) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2024.107575 · Cited by 21
Structural basis for the dynamic regulation of mTORC1 by amino acids
Valenstein, M. L., Wranik, M., Lalgudi, P. V., Linde-Garelli, K. Y., Choi, Y., Chivukula, R. R., Sabatini, D. M., & Rogala, K. B. (2025) · Nature · doi:10.1038/s41586-025-09428-7 · Cited by 24
Self-citationLi, J., Zhang, Y., Peng, J., Yang, W., Pan, Y., Xu, Y., Yao, J., Lin, S., Li, Y., Gu, X., et al. (2025) · Molecular Cell · doi:10.1016/j.molcel.2025.08.009 · Cited by 22
BCKA down-regulates mTORC2-Akt signal and enhances apoptosis susceptibility in cardiomyocytes
Guo, X., Huang, C., Lian, K., Wang, S., Zhao, H., Yan, F., Zhang, X., Zhang, J., Xie, H., An, R. F., et al. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.09.162 · Cited by 21
Li, Y., Han, B., Liu, L., Zhao, F., Liang, W., Jiang, J., Yang, Y., Ma, Z., & Sun, D. (2019) · Animal Genetics · doi:10.1111/age.12750 · Cited by 22
Sestrins: Darkhorse in the regulation of mitochondrial health and metabolism
Kumar, A. A., Dhiman, D., & Shaha, C. (2020) · Molecular Biology Reports · doi:10.1007/s11033-020-05769-w · Cited by 23
Endogenous Metabolic Modulators: Emerging Therapeutic Potential of Amino Acids
Hamill, M. J., Afeyan, R., Chakravarthy, M. V., & Tramontin, T. (2020) · iScience · doi:10.1016/j.isci.2020.101628 · Cited by 24
Autophagy compensates for Lkb1 loss to maintain adult mice homeostasis and survival
Khayati, K., Bhatt, V. D., Hu, Z. S., Fahumy, S., Luo, X., & Guo, J. Y. (2020) · eLife · doi:10.7554/elife.62377 · Cited by 21
Sestrin2 in hypoxia and hypoxia-related diseases
Che, X., Chai, J., Fang, Y., Zhang, X., Zu, A., Li, L., Sun, S., & Yang, W. (2021) · Redox Report · doi:10.1080/13510002.2021.1948774 · Cited by 23
Srivastava, A., Lu, J., Gadalla, D. S., Hendrich, O., Grönke, S., & Partridge, L. (2022) · Frontiers in Aging · doi:10.3389/fragi.2022.944466 · Cited by 21
Wang, G., Zhang, J., Wu, S., Qin, S., Zheng, Y., Xia, C., Geng, H., Yao, J., & Deng, L. (2022) · Animal nutrition · doi:10.1016/j.aninu.2022.07.010 · Cited by 23
Aging, Skeletal Muscle, and Epigenetics
Stewart, C. E., & Sharples, A. P. (2021) · Plastic & Reconstructive Surgery · doi:10.1097/prs.0000000000009670 · Cited by 22
Holowaty, M. N. H., Lees, M. J., Sawan, S. A., Paulussen, K. J. M., Jäger, R., Purpura, M., Paluska, S. A., Burd, N. A., Hodson, N. W., & Moore, D. R. (2022) · Amino Acids · doi:10.1007/s00726-022-03221-w · Cited by 24
Wei, P., He, Q., Liu, T., Zhang, J., Shi, K., Zhang, J., & Liu, S. (2022) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2022.116095 · Cited by 22
Sestrin2 Signaling Pathway Regulates Podocyte Biology and Protects against Diabetic Nephropathy
Ala, M. (2023) · Journal of Diabetes Research · doi:10.1155/2023/8776878 · Cited by 22
The Regulation and Double-Edged Roles of the Deubiquitinase OTUD5
Fu, L., Lu, K., Jiao, Q., Chen, X., & Jia, F. (2023) · Cells · doi:10.3390/cells12081161 · Cited by 26
Metabolism of glucose activates TORC1 through multiple mechanisms in Saccharomyces cerevisiae
Alfatah, M., Cui, L., Goh, C. J. H., Cheng, T. Y. N., Zhang, Y., Naaz, A., Wong, J. H., Lewis, J., Poh, W. J., & Arumugam, P. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.113205 · Cited by 22
Verhagen, F. H., Stigter, E. C. A., Pras‐Raves, M. L., Burgering, B. M. T., Imhof, S. M., Radstake, T. R. D. J., de Boer, J. H., & Kuiper, J. J. W. (2018) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2018.10.004 · Cited by 22
Wang, X., Liu, W., Zhuang, D., Hong, S., & Chen, J. (2017) · Oncotarget · doi:10.18632/oncotarget.21487 · Cited by 22
Metadata
- Authors
- Wolfson, R. L., Chantranupong, L., Saxton, R. A., Shen, K., Scaria, S. M., Cantor, J. R., & Sabatini, D. M.
- Affiliations
- Broad Institute (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Wolfson, Rachel L.
- Chantranupong, Lynne
- Sabatini, David M.
- ORCID
- Venue
- Science
- Published
- 2016-01
- Volume
- 351
- Issue
- 6268
- Pages
- 43-48
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4698017
- OpenAlex
- W2206269655
- Cited by
- 1,306
- References
- 47
- Citations by year
- 2026: 121 · 2025: 132 · 2024: 126 · 2023: 127 · 2022: 145 · 2021: 154 · 2020: 128 · 2019: 85 · 2018: 103 · 2017: 94 · 2016: 86
- FWCI
- 41.66
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- Department of Defense (W81XWH-07-0448)
- NIH (R01 CA103866, AI47389, T32 GM007753, F30 CA189333, F31 CA180271)
- Paul Gray Undergraduate Research Opportunities Program Fund (3143900)
- Pfizer Fellow of the Life Sciences Research Foundation
- Howard Hughes Medical Institute
- 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
- Sestrin2, leucine sensing, mTORC1, GATOR2, amino acid signaling, raptors, cell growth regulation, metabolic control, therapeutic target
- MeSH terms
- Mechanistic Target of Rapamycin Complex 1, Sestrins, Humans, Leucine, Nuclear Proteins, Protein Binding, Proteins, Signal Transduction, GTPase-Activating Proteins, Multiprotein Complexes, Metabolic Networks and Pathways, HEK293 Cells, TOR Serine-Threonine Kinases
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