Disruption of the Rag-Ragulator Complex by c17orf59 Inhibits mTORC1
mTORC1 controls key processes that regulate cell growth, including mRNA translation, ribosome biogenesis, and autophagy. Environmental amino acids activate mTORC1 by promoting its recruitment to the cytosolic surface of the lysosome, where its kinase is activated downstream of growth factor signalin...
| Main Authors: | , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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Elsevier
2017
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| Online Access: | http://hdl.handle.net/1721.1/109108 https://orcid.org/0000-0001-9765-4016 https://orcid.org/0000-0002-1446-7256 |
| _version_ | 1811074214653853696 |
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| author | Comb, William C. Schweitzer, Lawrence David Bar-Peled, Liron Sabatini, David |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Comb, William C. Schweitzer, Lawrence David Bar-Peled, Liron Sabatini, David |
| author_sort | Comb, William C. |
| collection | MIT |
| description | mTORC1 controls key processes that regulate cell growth, including mRNA translation, ribosome biogenesis, and autophagy. Environmental amino acids activate mTORC1 by promoting its recruitment to the cytosolic surface of the lysosome, where its kinase is activated downstream of growth factor signaling. mTORC1 is brought to the lysosome by the Rag GTPases, which are tethered to the lysosomal membrane by Ragulator, a lysosome-bound scaffold. Here, we identify c17orf59 as a Ragulator-interacting protein that regulates mTORC1 activity through its interaction with Ragulator at the lysosome. The binding of c17orf59 to Ragulator prevents Ragulator interaction with the Rag GTPases, both in cells and in vitro, and decreases Rag GTPase lysosomal localization. Disruption of the Rag-Ragulator interaction by c17orf59 impairs mTORC1 activation by amino acids by preventing mTOR from reaching the lysosome. By disrupting the Rag-Ragulator interaction to inhibit mTORC1, c17orf59 expression may represent another mechanism to modulate nutrient sensing by mTORC1. |
| first_indexed | 2024-09-23T09:45:46Z |
| format | Article |
| id | mit-1721.1/109108 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:45:46Z |
| publishDate | 2017 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1091082022-09-26T13:33:11Z Disruption of the Rag-Ragulator Complex by c17orf59 Inhibits mTORC1 Comb, William C. Schweitzer, Lawrence David Bar-Peled, Liron Sabatini, David Massachusetts Institute of Technology. Department of Biology Schweitzer, Lawrence David Bar-Peled, Liron Sabatini, David mTORC1 controls key processes that regulate cell growth, including mRNA translation, ribosome biogenesis, and autophagy. Environmental amino acids activate mTORC1 by promoting its recruitment to the cytosolic surface of the lysosome, where its kinase is activated downstream of growth factor signaling. mTORC1 is brought to the lysosome by the Rag GTPases, which are tethered to the lysosomal membrane by Ragulator, a lysosome-bound scaffold. Here, we identify c17orf59 as a Ragulator-interacting protein that regulates mTORC1 activity through its interaction with Ragulator at the lysosome. The binding of c17orf59 to Ragulator prevents Ragulator interaction with the Rag GTPases, both in cells and in vitro, and decreases Rag GTPase lysosomal localization. Disruption of the Rag-Ragulator interaction by c17orf59 impairs mTORC1 activation by amino acids by preventing mTOR from reaching the lysosome. By disrupting the Rag-Ragulator interaction to inhibit mTORC1, c17orf59 expression may represent another mechanism to modulate nutrient sensing by mTORC1. United States. National Institutes of Health (R01 CA129105) United States. National Institutes of Health (R37 AI047389) United States. National Institutes of Health (R01 CA103866) United States. National Institutes of Health (R37 AI047389) United States. National Institutes of Health (R21 AG042876-01A1) United States. Department of Defense (W81XWH-07-0448) United States. National Institutes of Health (F31 CA167872) American Cancer Society (PF-13-356-01-TBE) 2017-05-16T15:37:01Z 2017-05-16T15:37:01Z 2015-08 2015-07 Article http://purl.org/eprint/type/JournalArticle 2211-1247 http://hdl.handle.net/1721.1/109108 Schweitzer, Lawrence D.; Comb, William C.; Bar-Peled, Liron and Sabatini, David M. “Disruption of the Rag-Ragulator Complex by C17orf59 Inhibits mTORC1.” Cell Reports 12, no. 9 (September 2015): 1445–1455. © 2015 The Authors https://orcid.org/0000-0001-9765-4016 https://orcid.org/0000-0002-1446-7256 en_US http://dx.doi.org/10.1016/j.celrep.2015.07.052 Cell Reports Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Comb, William C. Schweitzer, Lawrence David Bar-Peled, Liron Sabatini, David Disruption of the Rag-Ragulator Complex by c17orf59 Inhibits mTORC1 |
| title | Disruption of the Rag-Ragulator Complex by c17orf59 Inhibits mTORC1 |
| title_full | Disruption of the Rag-Ragulator Complex by c17orf59 Inhibits mTORC1 |
| title_fullStr | Disruption of the Rag-Ragulator Complex by c17orf59 Inhibits mTORC1 |
| title_full_unstemmed | Disruption of the Rag-Ragulator Complex by c17orf59 Inhibits mTORC1 |
| title_short | Disruption of the Rag-Ragulator Complex by c17orf59 Inhibits mTORC1 |
| title_sort | disruption of the rag ragulator complex by c17orf59 inhibits mtorc1 |
| url | http://hdl.handle.net/1721.1/109108 https://orcid.org/0000-0001-9765-4016 https://orcid.org/0000-0002-1446-7256 |
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