Twenty-five years of mTOR: Uncovering the link from nutrients to growth
In my PNAS Inaugural Article, I describe the development of the mTOR field, starting with efforts to understand the mechanism of action of the drug rapamycin, which ∼25 y ago led to the discovery of the mTOR protein kinase. I focus on insights that we have contributed and on work that has been parti...
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| Format: | Article |
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Proceedings of the National Academy of Sciences
2018
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| Online Access: | http://hdl.handle.net/1721.1/116330 https://orcid.org/0000-0002-1446-7256 |
| _version_ | 1826215260617441280 |
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| author | Sabatini, David |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Sabatini, David |
| author_sort | Sabatini, David |
| collection | MIT |
| description | In my PNAS Inaugural Article, I describe the development of the mTOR field, starting with efforts to understand the mechanism of action of the drug rapamycin, which ∼25 y ago led to the discovery of the mTOR protein kinase. I focus on insights that we have contributed and on work that has been particularly influential to me, as well as provide some personal reflections and stories. We now appreciate that, as part of two distinct complexes, mTORC1 and mTORC2, mTOR is the major regulator of growth (mass accumulation) in animals and is the key link between the availability of nutrients in the environment and the control of most anabolic and catabolic processes. Nutrients signal to mTORC1 through the lysosome-associated Rag GTPases and their many regulators and associated cytosolic and lysosomal nutrient sensors. mTOR signaling is deregulated in common diseases, like cancer and epilepsy, and mTORC1 is a well-validated modulator of aging in multiple model organisms. There is significant excitement around using mTORC1 inhibitors to treat cancer and neurological disease and, potentially, to improve healthspan and lifespan. Keywords: mTOR; rapamycin; nutrients; Rag GTPase; growth |
| first_indexed | 2024-09-23T16:20:42Z |
| format | Article |
| id | mit-1721.1/116330 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T16:20:42Z |
| publishDate | 2018 |
| publisher | Proceedings of the National Academy of Sciences |
| record_format | dspace |
| spelling | mit-1721.1/1163302022-10-02T07:47:36Z Twenty-five years of mTOR: Uncovering the link from nutrients to growth Sabatini, David Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Sabatini, David In my PNAS Inaugural Article, I describe the development of the mTOR field, starting with efforts to understand the mechanism of action of the drug rapamycin, which ∼25 y ago led to the discovery of the mTOR protein kinase. I focus on insights that we have contributed and on work that has been particularly influential to me, as well as provide some personal reflections and stories. We now appreciate that, as part of two distinct complexes, mTORC1 and mTORC2, mTOR is the major regulator of growth (mass accumulation) in animals and is the key link between the availability of nutrients in the environment and the control of most anabolic and catabolic processes. Nutrients signal to mTORC1 through the lysosome-associated Rag GTPases and their many regulators and associated cytosolic and lysosomal nutrient sensors. mTOR signaling is deregulated in common diseases, like cancer and epilepsy, and mTORC1 is a well-validated modulator of aging in multiple model organisms. There is significant excitement around using mTORC1 inhibitors to treat cancer and neurological disease and, potentially, to improve healthspan and lifespan. Keywords: mTOR; rapamycin; nutrients; Rag GTPase; growth 2018-06-15T14:22:37Z 2018-06-15T14:22:37Z 2017-10 2017-09 2018-06-13T15:55:52Z Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/116330 Sabatini, David M. “Twenty-Five Years of mTOR: Uncovering the Link from Nutrients to Growth.” Proceedings of the National Academy of Sciences 114, 45 (October 2017): 11818–11825 © 2017 National Academy of Sciences https://orcid.org/0000-0002-1446-7256 http://dx.doi.org/10.1073/PNAS.1716173114 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Proceedings of the National Academy of Sciences PNAS |
| spellingShingle | Sabatini, David Twenty-five years of mTOR: Uncovering the link from nutrients to growth |
| title | Twenty-five years of mTOR: Uncovering the link from nutrients to growth |
| title_full | Twenty-five years of mTOR: Uncovering the link from nutrients to growth |
| title_fullStr | Twenty-five years of mTOR: Uncovering the link from nutrients to growth |
| title_full_unstemmed | Twenty-five years of mTOR: Uncovering the link from nutrients to growth |
| title_short | Twenty-five years of mTOR: Uncovering the link from nutrients to growth |
| title_sort | twenty five years of mtor uncovering the link from nutrients to growth |
| url | http://hdl.handle.net/1721.1/116330 https://orcid.org/0000-0002-1446-7256 |
| work_keys_str_mv | AT sabatinidavid twentyfiveyearsofmtoruncoveringthelinkfromnutrientstogrowth |