Amino acids and mTORC1: from lysosomes to disease.
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| Abstract | The mechanistic target of rapamycin (mTOR) kinase controls growth and metabolism, and its deregulation underlies the pathogenesis of many diseases, including cancer, neurodegeneration, and diabetes. mTOR complex 1 (mTORC1) integrates signals arising from nutrients, energy, and growth factors, but how exactly these signals are propagated await to be fully understood. Recent findings have placed the lysosome, a key mediator of cellular catabolism, at the core of mTORC1 regulation by amino acids. A multiprotein complex that includes the Rag GTPases, Ragulator, and the v-ATPase forms an amino acid-sensing machinery on the lysosomal surface that affects the decision between cell growth and catabolism at multiple levels. The involvement of a catabolic organelle in growth signaling may have important implications for our understanding of mTORC1-related pathologies. |
| Year of Publication | 2012
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| Journal | Trends Mol Med
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| Volume | 18
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| Issue | 9
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| Pages | 524-33
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| Date Published | 2012 Sep
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| ISSN | 1471-499X
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| URL | |
| DOI | 10.1016/j.molmed.2012.05.007
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| PubMed ID | 22749019
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| PubMed Central ID | PMC3432651
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| Grant list | R01 CA103866 / CA / NCI NIH HHS / United States
R01 CA129105 / CA / NCI NIH HHS / United States
R37 AI047389 / AI / NIAID NIH HHS / United States
Howard Hughes Medical Institute / United States
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