| Amino acids and mTORC1: from lysosomes to disease. | |
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MedLine Citation:
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PMID: 22749019 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Alejo Efeyan; Roberto Zoncu; David M Sabatini |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review Date: 2012-06-28 |
Journal Detail:
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Title: Trends in molecular medicine Volume: 18 ISSN: 1471-499X ISO Abbreviation: Trends Mol Med Publication Date: 2012 Sep |
Date Detail:
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Created Date: 2012-09-03 Completed Date: 2013-01-16 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 100966035 Medline TA: Trends Mol Med Country: England |
Other Details:
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Languages: eng Pagination: 524-33 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 Elsevier Ltd. All rights reserved. |
Affiliation:
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Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acids
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metabolism* Diabetes Mellitus / metabolism Humans Lysosomes / metabolism* Multiprotein Complexes / genetics, metabolism* Neoplasms / metabolism Neurodegenerative Diseases / metabolism TOR Serine-Threonine Kinases / genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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R01 CA103866/CA/NCI NIH HHS; R01 CA103866/CA/NCI NIH HHS; R01 CA129105/CA/NCI NIH HHS; R01 CA129105/CA/NCI NIH HHS; R37 AI047389/AI/NIAID NIH HHS; R37 AI047389/AI/NIAID NIH HHS; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
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0/Amino Acids; 0/Multiprotein Complexes; 0/TOR complex 1; EC 2.7.1.1/TOR Serine-Threonine Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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