Sestrin2 inhibits mTORC1 through modulation of GATOR complexes
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kim, Jeong Sig | - |
dc.contributor.author | Ro, Seung-Hyun | - |
dc.contributor.author | Kim, Myungjin | - |
dc.contributor.author | Park, Hwan-Woo | - |
dc.contributor.author | Semple, Ian A. | - |
dc.contributor.author | Park, Haeli | - |
dc.contributor.author | Cho, Uhn-Soo | - |
dc.contributor.author | Wang, Wei | - |
dc.contributor.author | Guan, Kun-Liang | - |
dc.contributor.author | Karin, Michael | - |
dc.contributor.author | Lee, Jun Hee | - |
dc.date.accessioned | 2021-08-11T20:26:32Z | - |
dc.date.available | 2021-08-11T20:26:32Z | - |
dc.date.issued | 2015-03-30 | - |
dc.identifier.issn | 2045-2322 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/10782 | - |
dc.description.abstract | Sestrins are stress-inducible metabolic regulators that suppress a wide range of age- and obesity-associated pathologies, many of which are due to mTORC1 overactivation. Upon various stresses, the Sestrins inhibit mTORC1 activity through an indirect mechanism that is still unclear. GATORs are recently identified protein complexes that regulate the activity of RagB, a small GTPase essential for mTORC1 activation. GATOR1 is a GTPase activating protein (GAP) for RagB whereas GATOR2 functions as an inhibitor of GATOR1. However, how the GATORs are physiologically regulated is unknown. Here we show that Sestrin2 binds to GATOR2, and liberates GATOR1 from GATOR2-mediated inhibition. Released GATOR1 subsequently binds to and inactivates RagB, ultimately resulting in mTORC1 suppression. Consistent with this biochemical mechanism, genetic ablation of GATOR1 nullifies the mTORC1-inhibiting effect of Sestrin2 in both cell culture and Drosophila models. Collectively, we elucidate a new signaling cascade composed of Sestrin2-GATOR2-GATOR1-RagB that mediates stress-dependent suppression of mTORC1 activity. | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | Nature Publishing Group | - |
dc.title | Sestrin2 inhibits mTORC1 through modulation of GATOR complexes | - |
dc.type | Article | - |
dc.publisher.location | 영국 | - |
dc.identifier.doi | 10.1038/srep09502 | - |
dc.identifier.scopusid | 2-s2.0-84961291783 | - |
dc.identifier.wosid | 000351942700001 | - |
dc.identifier.bibliographicCitation | Scientific Reports, v.5 | - |
dc.citation.title | Scientific Reports | - |
dc.citation.volume | 5 | - |
dc.type.docType | Article | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.subject.keywordPlus | AMINO-ACID LEVELS | - |
dc.subject.keywordPlus | RAG GTPASES | - |
dc.subject.keywordPlus | TUMOR-SUPPRESSOR | - |
dc.subject.keywordPlus | TORC1 | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | STRESS | - |
dc.subject.keywordPlus | FAMILY | - |
dc.subject.keywordPlus | AMPK | - |
dc.subject.keywordPlus | GAP | - |
dc.subject.keywordPlus | PHOSPHORYLATION | - |
dc.subject.keywordAuthor | Sestrin2 inhibits mTORC1 through modulation of GATOR complexes | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
(31538) 22, Soonchunhyang-ro, Asan-si, Chungcheongnam-do, Republic of Korea+82-41-530-1114
COPYRIGHT 2021 by SOONCHUNHYANG UNIVERSITY ALL RIGHTS RESERVED.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.