{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRPTOR (regulatory‐associated protein of mTOR) is a critical scaffolding component of mTOR complex 1 (mTORC1) that recruits key substrates (such as 4E‐BP1 and p70 S6 kinase) to the complex, thereby mediating the response of cells to nutrients, growth factors, and energetic cues. Under conditions of energy stress, for example, AMPK phosphorylates RPTOR, promoting 14-3-3 binding and contributing to the inhibition of mTORC1 activity and consequent cell cycle arrest. In nutrient‐rich or hormone‐stimulated states, RPTOR’s association with mTOR supports protein-synthetic signaling that influences cell size and growth."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRPTOR function is intricately modulated by posttranslational modifications and protein–protein interactions. Multiple kinases—including ERK1/2, ULK1, JNK, and ICK—phosphorylate specific serine/threonine residues on RPTOR, thereby regulating its ability to dock substrates and modulating mTORC1 activity. High-resolution structural studies have revealed that RPTOR’s α-solenoid domain and a “claw” region detect the nucleotide state of Rag GTPases, ensuring mTORC1 is correctly targeted to the lysosomal membrane where it becomes activated. In addition, environmental redox conditions and stabilization by deubiquitylating enzymes such as USP9X further fine-tune RPTOR levels and function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAberrant regulation of RPTOR and, by extension, mTORC1 signaling is implicated in a wide range of pathological conditions. Altered RPTOR expression or mutation is associated with metabolic disturbances—including insulin resistance and obesity—and genetic studies have linked RPTOR variants with altered cancer risk. Dysregulated RPTOR/mTORC1 activity contributes to viral infections, aberrant vascular remodeling, and the progression of hormone-responsive tumours such as prostate and triple-negative breast cancers. Furthermore, RPTOR plays roles in cell cycle progression and autophagy, and its perturbation has been observed in diverse neoplasms such as glioblastoma, gastric cancer, colorectal carcinoma, and even in disorders of normal tissue development. These insights underscore the potential of targeting the RPTOR/mTORC1 axis for therapeutic intervention in metabolic diseases and cancer."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "19", "end_ref": "36"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Do-Hyung Kim, D D Sarbassov, Siraj M Ali, et al. "}, {"type": "b", "children": [{"type": "t", "text": "mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0092-8674(02)00808-5"}], "href": "https://doi.org/10.1016/s0092-8674(02"}, {"type": "t", "text": "00808-5) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12150925"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12150925"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kenta Hara, Yoshiko Maruki, Xiaomeng Long, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0092-8674(02)00833-4"}], "href": "https://doi.org/10.1016/s0092-8674(02"}, {"type": "t", "text": "00833-4) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12150926"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12150926"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Hiroki Nojima, Chiharu Tokunaga, Satoshi Eguchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.C200665200"}], "href": "https://doi.org/10.1074/jbc.C200665200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12604610"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12604610"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Alexandros Tzatsos, Konstantin V Kandror "}, {"type": "b", "children": [{"type": "t", "text": "Nutrients suppress phosphatidylinositol 3-kinase/Akt signaling via raptor-dependent mTOR-mediated insulin receptor substrate 1 phosphorylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.26.1.63-76.2006"}], "href": "https://doi.org/10.1128/MCB.26.1.63-76.2006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16354680"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16354680"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Dana M Gwinn, David B Shackelford, Daniel F Egan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AMPK phosphorylation of raptor mediates a metabolic checkpoint."}]}, {"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.2008.03.003"}], "href": "https://doi.org/10.1016/j.molcel.2008.03.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18439900"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18439900"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Audrey Carrière, Marie Cargnello, Louis-André Julien, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Oncogenic MAPK signaling stimulates mTORC1 activity by promoting RSK-mediated raptor phosphorylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cub.2008.07.078"}], "href": "https://doi.org/10.1016/j.cub.2008.07.078"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18722121"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18722121"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Dos D Sarbassov, David M Sabatini "}, {"type": "b", "children": [{"type": "t", "text": "Redox regulation of the nutrient-sensitive raptor-mTOR pathway and complex."}]}, {"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.M506096200"}], "href": "https://doi.org/10.1074/jbc.M506096200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16183647"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16183647"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "O Jameel Shah, Tony Hunter "}, {"type": "b", "children": [{"type": "t", "text": "Turnover of the active fraction of IRS1 involves raptor-mTOR- and S6K1-dependent serine phosphorylation in cell culture models of tuberous sclerosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.01254-05"}], "href": "https://doi.org/10.1128/MCB.01254-05"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16914728"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16914728"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Kathryn G Foster, Hugo A Acosta-Jaquez, Yves Romeo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of mTOR complex 1 (mTORC1) by raptor Ser863 and multisite phosphorylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.029637"}], "href": "https://doi.org/10.1074/jbc.M109.029637"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19864431"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19864431"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Audrey Carriere, Yves Romeo, Hugo A Acosta-Jaquez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ERK1/2 phosphorylate Raptor to promote Ras-dependent activation of mTOR complex 1 (mTORC1)."}]}, {"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.M110.159046"}], "href": "https://doi.org/10.1074/jbc.M110.159046"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21071439"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21071439"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Elaine A Dunlop, David K Hunt, Hugo A Acosta-Jaquez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ULK1 inhibits mTORC1 signaling, promotes multisite Raptor phosphorylation and hinders substrate binding."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Autophagy (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/auto.7.7.15491"}], "href": "https://doi.org/10.4161/auto.7.7.15491"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21460630"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21460630"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Di Wu, Jessica R Chapman, Lifu Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Intestinal cell kinase (ICK) promotes activation of mTOR complex 1 (mTORC1) through phosphorylation of Raptor Thr-908."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.302117"}], "href": "https://doi.org/10.1074/jbc.M111.302117"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22356909"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22356909"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Dongoh Kwak, Sunkyu Choi, Heeyoon Jeong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Osmotic stress regulates mammalian target of rapamycin (mTOR) complex 1 via c-Jun N-terminal Kinase (JNK)-mediated Raptor protein phosphorylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.326538"}], "href": "https://doi.org/10.1074/jbc.M111.326538"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22493283"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22493283"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Christian H Gabriel, Fridolin Gross, Martin Karl, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of Novel Nuclear Factor of Activated T Cell (NFAT)-associated Proteins in T Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M116.739326"}], "href": "https://doi.org/10.1074/jbc.M116.739326"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27637333"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27637333"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Caitlin R Bridges, Men-Chee Tan, Susitha Premarathne, et al. "}, {"type": "b", "children": [{"type": "t", "text": "USP9X deubiquitylating enzyme maintains RAPTOR protein levels, mTORC1 signalling and proliferation in neural progenitors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-017-00149-0"}], "href": "https://doi.org/10.1038/s41598-017-00149-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28341829"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28341829"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Kacper B Rogala, Xin Gu, Jibril F Kedir, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural basis for the docking of mTORC1 on the lysosomal surface."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.aay0166"}], "href": "https://doi.org/10.1126/science.aay0166"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31601708"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31601708"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Madhanagopal Anandapadamanaban, Glenn R Masson, Olga Perisic, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Architecture of human Rag GTPase heterodimers and their complex with mTORC1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.aax3939"}], "href": "https://doi.org/10.1126/science.aax3939"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31601764"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31601764"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Raphael Böhm, Stefan Imseng, Roman P Jakob, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The dynamic mechanism of 4E-BP1 recognition and phosphorylation by mTORC1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2021.03.031"}], "href": "https://doi.org/10.1016/j.molcel.2021.03.031"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33852892"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33852892"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Sagar B Kudchodkar, Yongjun Yu, Tobi G Maguire, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human cytomegalovirus infection alters the substrate specificities and rapamycin sensitivities of raptor- and rictor-containing complexes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0605825103"}], "href": "https://doi.org/10.1073/pnas.0605825103"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16959881"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16959881"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Bryan C Fuchs, Richard E Finger, Marie C Onan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ASCT2 silencing regulates mammalian target-of-rapamycin growth and survival signaling in human hepatoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Cell Physiol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpcell.00330.2006"}], "href": "https://doi.org/10.1152/ajpcell.00330.2006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17329400"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17329400"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Yinong Wang, Yalai Bai, Lingfeng Qin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interferon-gamma induces human vascular smooth muscle cell proliferation and intimal expansion by phosphatidylinositol 3-kinase dependent mammalian target of rapamycin raptor complex 1 activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCRESAHA.107.151068"}], "href": "https://doi.org/10.1161/CIRCRESAHA.107.151068"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17656678"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17656678"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Y Wang, M Mikhailova, S Bose, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of androgen receptor transcriptional activity by rapamycin in prostate cancer cell proliferation and survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2008.318"}], "href": "https://doi.org/10.1038/onc.2008.318"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18776922"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18776922"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "M Rosner, N Siegel, A Valli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "mTOR phosphorylated at S2448 binds to raptor and rictor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Amino Acids (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00726-008-0230-7"}], "href": "https://doi.org/10.1007/s00726-008-0230-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19145465"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19145465"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Nicholas Gulati, Michael Karsy, Ladislau Albert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Involvement of mTORC1 and mTORC2 in regulation of glioblastoma multiforme growth and motility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oncol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijo_00000386"}], "href": "https://doi.org/10.3892/ijo_00000386"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19724909"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19724909"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Jie Lin, Jianming Wang, Anthony J Greisinger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Energy balance, the PI3K-AKT-mTOR pathway genes, and the risk of bladder cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Prev Res (Phila) (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1940-6207.CAPR-09-0263"}], "href": "https://doi.org/10.1158/1940-6207.CAPR-09-0263"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20354165"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20354165"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Francisco Ramírez-Valle, Michelle L Badura, Steve Braunstein, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mitotic raptor promotes mTORC1 activity, G(2)/M cell cycle progression, and internal ribosome entry site-mediated mRNA translation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00322-09"}], "href": "https://doi.org/10.1128/MCB.00322-09"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20439490"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20439490"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Sebastian Real, Nathalie Meo-Evoli, Lilia Espada, et al. "}, {"type": "b", "children": [{"type": "t", "text": "E2F1 regulates cellular growth by mTORC1 signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0016163"}], "href": "https://doi.org/10.1371/journal.pone.0016163"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21283628"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21283628"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Jing He, Meng-Yun Wang, Li-Xin Qiu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variations of mTORC1 genes and risk of gastric cancer in an Eastern Chinese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Carcinog (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mc.22013"}], "href": "https://doi.org/10.1002/mc.22013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23423739"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23423739"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Sonja I Berndt, Stefan Gustafsson, Reedik Mägi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.2606"}], "href": "https://doi.org/10.1038/ng.2606"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23563607"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23563607"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Nicoletta Bianchi, Alessia Finotti, Manuela Ferracin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increase of microRNA-210, decrease of raptor gene expression and alteration of mammalian target of rapamycin regulated proteins following mithramycin treatment of human erythroid cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0121567"}], "href": "https://doi.org/10.1371/journal.pone.0121567"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25849663"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25849663"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "A Alayev, R S Salamon, S M Berger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "mTORC1 directly phosphorylates and activates ERα upon estrogen stimulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2015.414"}], "href": "https://doi.org/10.1038/onc.2015.414"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26522726"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26522726"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Fredrick J Rosario, Kris Genelyn Dimasuay, Yoshikatsu Kanai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of amino acid transporter trafficking by mTORC1 in primary human trophoblast cells is mediated by the ubiquitin ligase Nedd4-2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Sci (Lond) (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/CS20150554"}], "href": "https://doi.org/10.1042/CS20150554"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26608079"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26608079"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Reza Aghamohammadzadeh, Ying-Yi Zhang, Thomas E Stephens, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Up-regulation of the mammalian target of rapamycin complex 1 subunit Raptor by aldosterone induces abnormal pulmonary artery smooth muscle cell survival patterns to promote pulmonary arterial hypertension."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.201500042"}], "href": "https://doi.org/10.1096/fj.201500042"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27006450"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27006450"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Qiuqiong Tang, Tim Holland-Letz, Alla Slynko, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DNA methylation array analysis identifies breast cancer associated RPTOR, MGRN1 and RAPSN hypomethylation in peripheral blood DNA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.11640"}], "href": "https://doi.org/10.18632/oncotarget.11640"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27577081"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27577081"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Kyu Sic You, Yong Weon Yi, Sahng-June Kwak, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of RPTOR overcomes resistance to EGFR inhibition in triple-negative breast cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oncol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijo.2018.4244"}], "href": "https://doi.org/10.3892/ijo.2018.4244"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29344641"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29344641"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Tao Wang, Wei-Sheng Zhang, Zheng-Xia Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RAPTOR promotes colorectal cancer proliferation by inducing mTORC1 and upregulating ribosome assembly factor URB1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Med (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cam4.2810"}], "href": "https://doi.org/10.1002/cam4.2810"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31886628"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31886628"}]}]}]}