{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe collection of abstracts provided offers a broad overview of the intricate regulation of cell growth, metabolism, and survival mediated by the tuberous sclerosis complex (TSC1/TSC2) and its downstream effector, the mammalian target of rapamycin (mTOR) pathway. These studies detail how various signals—including cellular energy levels, nutrient availability, growth factors, stressors, and hormonal cues—affect mTOR activity via upstream regulators such as AMPK, Akt, Rheb, and others. In a range of systems—from neural cells and pancreatic β cells to renal, hepatic, and immune models—deregulation of this pathway is shown to impact translation, autophagy, apoptosis, and differentiation, thereby contributing to diverse pathologies such as tuberous sclerosis, tumor syndromes, diabetes, and even facets of aging and immunity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "42"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIt is important to note that none of the abstracts mention or discuss RPP38. RPP38 is generally recognized as a protein subunit of the ribonuclease P (RNase P) complex, which plays a role in the processing of precursor tRNAs. However, within the context of these studies—which are predominantly focused on the regulation of mTOR signaling via the TSC1/TSC2 complex and its impact on cellular growth, metabolism, and stress responses—no direct insights or experimental findings were provided regarding the function, regulation, or clinical significance of RPP38.\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn summary, while the provided literature substantially advances our understanding of TSC/mTOR signaling in various physiological and pathological conditions, they do not offer any data pertaining to RPP38 function. Future investigations would be required to determine whether RPP38 intersects with these signaling networks or functions independently in RNA processing and other cellular processes.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Brendan D Manning, Andrew R Tee, M Nicole Logsdon, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Loss of Tsc1/Tsc2 activates mTOR and disrupts PI3K-Akt signaling through downregulation of PDGFR."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI17222"}], "href": "https://doi.org/10.1172/JCI17222"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14561707"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14561707"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ken Inoki, Tianqing Zhu, Kun-Liang Guan "}, {"type": "b", "children": [{"type": "t", "text": "TSC2 mediates cellular energy response to control cell growth and survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0092-8674(03)00929-2"}], "href": "https://doi.org/10.1016/s0092-8674(03"}, {"type": "t", "text": "00929-2) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14651849"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14651849"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Laura S Harrington, Greg M Findlay, Alex Gray, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200403069"}], "href": "https://doi.org/10.1083/jcb.200403069"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15249583"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15249583"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "James Brugarolas, Kui Lei, Rebecca L Hurley, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.1256804"}], "href": "https://doi.org/10.1101/gad.1256804"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15545625"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15545625"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ewan M Smith, Stephen G Finn, Andrew R Tee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The tuberous sclerosis protein TSC2 is not required for the regulation of the mammalian target of rapamycin by amino acids and certain cellular stresses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M414499200"}], "href": "https://doi.org/10.1074/jbc.M414499200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15772076"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15772076"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Brendan D Manning, M Nicole Logsdon, Alex I Lipovsky, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Feedback inhibition of Akt signaling limits the growth of tumors lacking Tsc2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.1314605"}], "href": "https://doi.org/10.1101/gad.1314605"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16027169"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16027169"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Sohail F Tavazoie, Veronica A Alvarez, Dennis A Ridenour, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of neuronal morphology and function by the tumor suppressors Tsc1 and Tsc2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Neurosci (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nn1566"}], "href": "https://doi.org/10.1038/nn1566"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16286931"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16286931"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Changhua Wang, Xuming Mao, Lixin Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adiponectin sensitizes insulin signaling by reducing p70 S6 kinase-mediated serine phosphorylation of IRS-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M700098200"}], "href": "https://doi.org/10.1074/jbc.M700098200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17244624"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17244624"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Benoit Bilanges, Rhoda Argonza-Barrett, Marina Kolesnichenko, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tuberous sclerosis complex proteins 1 and 2 control serum-dependent translation in a TOP-dependent and -independent manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.02136-06"}], "href": "https://doi.org/10.1128/MCB.02136-06"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17562867"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17562867"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Chung-Han Lee, Ken Inoki, Magdalena Karbowniczek, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Constitutive mTOR activation in TSC mutants sensitizes cells to energy starvation and genomic damage via p53."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.emboj.7601900"}], "href": "https://doi.org/10.1038/sj.emboj.7601900"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17962806"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17962806"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Yutaka Shigeyama, Toshiyuki Kobayashi, Yoshiaki Kido, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biphasic response of pancreatic beta-cell mass to ablation of tuberous sclerosis complex 2 in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.01695-07"}], "href": "https://doi.org/10.1128/MCB.01695-07"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18316403"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18316403"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Umut Ozcan, Lale Ozcan, Erkan Yilmaz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of the tuberous sclerosis complex tumor suppressors triggers the unfolded protein response to regulate insulin signaling and apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2007.12.023"}], "href": "https://doi.org/10.1016/j.molcel.2007.12.023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18342602"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18342602"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Jingxiang Huang, Christian C Dibble, Mika Matsuzaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The TSC1-TSC2 complex is required for proper activation of mTOR complex 2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00289-08"}], "href": "https://doi.org/10.1128/MCB.00289-08"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18411301"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18411301"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Dan Ehninger, Sangyeul Han, Carrie Shilyansky, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Reversal of learning deficits in a Tsc2+/- mouse model of tuberous sclerosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm1788"}], "href": "https://doi.org/10.1038/nm1788"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18568033"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18568033"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Latif Rachdi, Norman Balcazar, Fernando Osorio-Duque, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Disruption of Tsc2 in pancreatic beta cells induces beta cell mass expansion and improved glucose tolerance in a TORC1-dependent manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0803047105"}], "href": "https://doi.org/10.1073/pnas.0803047105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18587048"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18587048"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Tiffiney R Hartman, Dongyan Liu, Jack T Zilfou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The tuberous sclerosis proteins regulate formation of the primary cilium via a rapamycin-insensitive and polycystin 1-independent pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddn325"}], "href": "https://doi.org/10.1093/hmg/ddn325"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18845692"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18845692"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Dung-Fang Lee, Hsu-Ping Kuo, Chun-Te Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IKKbeta suppression of TSC1 function links the mTOR pathway with insulin resistance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Med (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijmm_00000065"}], "href": "https://doi.org/10.3892/ijmm_00000065"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18949383"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18949383"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Ilona Patursky-Polischuk, Miri Stolovich-Rain, Mirit Hausner-Hanochi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The TSC-mTOR pathway mediates translational activation of TOP mRNAs by insulin largely in a raptor- or rictor-independent manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00980-08"}], "href": "https://doi.org/10.1128/MCB.00980-08"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19047368"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19047368"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Gianfranco Distefano, Manila Boca, Isaline Rowe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polycystin-1 regulates extracellular signal-regulated kinase-dependent phosphorylation of tuberin to control cell size through mTOR and its downstream effectors S6K and 4EBP1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.01259-08"}], "href": "https://doi.org/10.1128/MCB.01259-08"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19255143"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19255143"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Deepak Adhikari, Gilian Flohr, Nagaraju Gorre, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Disruption of Tsc2 in oocytes leads to overactivation of the entire pool of primordial follicles."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Hum Reprod (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/molehr/gap092"}], "href": "https://doi.org/10.1093/molehr/gap092"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19843635"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19843635"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Duyu Nie, Alessia Di Nardo, Juliette M Han, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tsc2-Rheb signaling regulates EphA-mediated axon guidance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Neurosci (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nn.2477"}], "href": "https://doi.org/10.1038/nn.2477"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20062052"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20062052"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Hiyaa Singhee Ghosh, Michael McBurney, Paul D Robbins "}, {"type": "b", "children": [{"type": "t", "text": "SIRT1 negatively regulates the mammalian target of rapamycin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0009199"}], "href": "https://doi.org/10.1371/journal.pone.0009199"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20169165"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20169165"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Y J Kang, M-K Lu, K-L Guan "}, {"type": "b", "children": [{"type": "t", "text": "The TSC1 and TSC2 tumor suppressors are required for proper ER stress response and protect cells from ER stress-induced apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Differ (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cdd.2010.82"}], "href": "https://doi.org/10.1038/cdd.2010.82"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20616807"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20616807"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Elizabeth A Barnes, Heidi L Kenerson, Xiuyun Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tuberin regulates E-cadherin localization: implications in epithelial-mesenchymal transition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2353/ajpath.2010.090233"}], "href": "https://doi.org/10.2353/ajpath.2010.090233"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20813961"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20813961"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Ling-Hui Zeng, Nicholas R Rensing, Bo Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tsc2 gene inactivation causes a more severe epilepsy phenotype than Tsc1 inactivation in a mouse model of tuberous sclerosis complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddq491"}], "href": "https://doi.org/10.1093/hmg/ddq491"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21062901"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21062901"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Nicholas C Wolff, Silvia Vega-Rubin-de-Celis, Xian-Jin Xie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cell-type-dependent regulation of mTORC1 by REDD1 and the tumor suppressors TSC1/TSC2 and LKB1 in response to hypoxia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.01393-10"}], "href": "https://doi.org/10.1128/MCB.01393-10"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21383064"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21383064"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "R Michelle Reith, Sharon Way, James McKenna, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of the tuberous sclerosis complex protein tuberin causes Purkinje cell degeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurobiol Dis (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.nbd.2011.02.014"}], "href": "https://doi.org/10.1016/j.nbd.2011.02.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21419848"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21419848"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Elena A Goncharova, Dmitry A Goncharov, Hua Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "mTORC2 is required for proliferation and survival of TSC2-null cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.01061-10"}], "href": "https://doi.org/10.1128/MCB.01061-10"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21482669"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21482669"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Sei Yoshida, Sungki Hong, Tsukasa Suzuki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Redox regulates mammalian target of rapamycin complex 1 (mTORC1) activity by modulating the TSC1/TSC2-Rheb GTPase pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.238014"}], "href": "https://doi.org/10.1074/jbc.M111.238014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21784859"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21784859"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Chang Hwa Jung, Minchul Seo, Neil Michael Otto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ULK1 inhibits the kinase activity of mTORC1 and cell proliferation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Autophagy (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/auto.7.10.16660"}], "href": "https://doi.org/10.4161/auto.7.10.16660"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21795849"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21795849"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Lianjun Zhang, Hongbing Zhang, Lanlan Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TSC1/2 signaling complex is essential for peripheral naïve CD8+ T cell survival and homeostasis in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0030592"}], "href": "https://doi.org/10.1371/journal.pone.0030592"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22363451"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22363451"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Hannah Crossland, Abid A Kazi, Charles H Lang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Focal adhesion kinase is required for IGF-I-mediated growth of skeletal muscle cells via a TSC2/mTOR/S6K1-associated pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Endocrinol Metab (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpendo.00541.2012"}], "href": "https://doi.org/10.1152/ajpendo.00541.2012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23695213"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23695213"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Rachel Miloslavski, Elad Cohen, Adam Avraham, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Oxygen sufficiency controls TOP mRNA translation via the TSC-Rheb-mTOR pathway in a 4E-BP-independent manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Cell Biol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/jmcb/mju008"}], "href": "https://doi.org/10.1093/jmcb/mju008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24627160"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24627160"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Y Zhou, P Rychahou, Q Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TSC2/mTORC1 signaling controls Paneth and goblet cell differentiation in the intestinal epithelium."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cddis.2014.588"}], "href": "https://doi.org/10.1038/cddis.2014.588"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25654764"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25654764"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Robin M Hobbs, Hue M La, Juho-Antti Mäkelä, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Distinct germline progenitor subsets defined through Tsc2-mTORC1 signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embr.201439379"}], "href": "https://doi.org/10.15252/embr.201439379"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25700280"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25700280"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Constantinos Demetriades, Monika Plescher, Aurelio A Teleman "}, {"type": "b", "children": [{"type": "t", "text": "Lysosomal recruitment of TSC2 is a universal response to cellular stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms10662"}], "href": "https://doi.org/10.1038/ncomms10662"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26868506"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26868506"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Cyndi R Morales, Dan L Li, Zully Pedrozo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of class I histone deacetylases blunts cardiac hypertrophy through TSC2-dependent mTOR repression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Signal (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/scisignal.aad5736"}], "href": "https://doi.org/10.1126/scisignal.aad5736"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27048565"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27048565"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Monika Linke, Ha Thi Thanh Pham, Karl Katholnig, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Chronic signaling via the metabolic checkpoint kinase mTORC1 induces macrophage granuloma formation and marks sarcoidosis progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni.3655"}], "href": "https://doi.org/10.1038/ni.3655"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28092373"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28092373"}]}, {"type": "r", "ref": 41, "children": [{"type": "t", "text": "Alexander J Valvezan, Marc Turner, Amine Belaid, et al. "}, {"type": "b", "children": [{"type": "t", "text": "mTORC1 Couples Nucleotide Synthesis to Nucleotide Demand Resulting in a Targetable Metabolic Vulnerability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccell.2017.09.013"}], "href": "https://doi.org/10.1016/j.ccell.2017.09.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29056426"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29056426"}]}, {"type": "r", "ref": 42, "children": [{"type": "t", "text": "Jeanine L Van Nostrand, Kristina Hellberg, En-Ching Luo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AMPK regulation of Raptor and TSC2 mediate metformin effects on transcriptional control of anabolism and inflammation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.339895.120"}], "href": "https://doi.org/10.1101/gad.339895.120"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32912901"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32912901"}]}]}]}