Tripartite suppression of fission yeast torc1 signaling by the gator1-sea3 complex, the tsc complex, and gcn2 kinase
Mammalian target of rapamycin complex 1 (TORC1) is controlled by the GATOR complex composed of the GATOR1 subcomplex and its inhibitor, the GATOR2 subcomplex, sensitive to amino acid starvation. Previously, we identified fission yeast GATOR1 that prevents deregulated activation of TORC1 (Chia et al....
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| Format: | Article |
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2021
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| author | Fukuda, T. Sofyantoro, F. Tai, Y.T. Chia, K.H. Matsuda, T. Murase, T. Morozumi, Y. Tatebe, H. Kanki, T. Shiozaki, K. |
| author_facet | Fukuda, T. Sofyantoro, F. Tai, Y.T. Chia, K.H. Matsuda, T. Murase, T. Morozumi, Y. Tatebe, H. Kanki, T. Shiozaki, K. |
| author_sort | Fukuda, T. |
| collection | UGM |
| description | Mammalian target of rapamycin complex 1 (TORC1) is controlled by the GATOR complex composed of the GATOR1 subcomplex and its inhibitor, the GATOR2 subcomplex, sensitive to amino acid starvation. Previously, we identified fission yeast GATOR1 that prevents deregulated activation of TORC1 (Chia et al., 2017). Here, we report identification and characterization of GATOR2 in fission yeast. Unexpectedly, the GATOR2 subunit Sea3, an ortholog of mammalian WDR59, is physically and functionally proximal to GATOR1, rather than GATOR2, attenuating TORC1 activity. The fission yeast GATOR complex is dispensable for TORC1 regulation in response to amino acid starvation, which instead activates the Gcn2 pathway to inhibit TORC1 and induce autophagy. On the other hand, nitrogen starvation suppresses TORC1 through the combined actions of the GATOR1-Sea3 complex, the Gcn2 pathway, and the TSC complex, another conserved TORC1 inhibitor. Thus, multiple, parallel signaling pathways implement negative regulation of TORC1 to ensure proper cellular starvation responses. © Fukuda et al. |
| first_indexed | 2024-03-14T00:03:05Z |
| format | Article |
| id | oai:generic.eprints.org:279113 |
| institution | Universiti Gadjah Mada |
| last_indexed | 2024-03-14T00:03:05Z |
| publishDate | 2021 |
| record_format | dspace |
| spelling | oai:generic.eprints.org:2791132023-11-02T02:18:47Z https://repository.ugm.ac.id/279113/ Tripartite suppression of fission yeast torc1 signaling by the gator1-sea3 complex, the tsc complex, and gcn2 kinase Fukuda, T. Sofyantoro, F. Tai, Y.T. Chia, K.H. Matsuda, T. Murase, T. Morozumi, Y. Tatebe, H. Kanki, T. Shiozaki, K. Neurosciences Mammalian target of rapamycin complex 1 (TORC1) is controlled by the GATOR complex composed of the GATOR1 subcomplex and its inhibitor, the GATOR2 subcomplex, sensitive to amino acid starvation. Previously, we identified fission yeast GATOR1 that prevents deregulated activation of TORC1 (Chia et al., 2017). Here, we report identification and characterization of GATOR2 in fission yeast. Unexpectedly, the GATOR2 subunit Sea3, an ortholog of mammalian WDR59, is physically and functionally proximal to GATOR1, rather than GATOR2, attenuating TORC1 activity. The fission yeast GATOR complex is dispensable for TORC1 regulation in response to amino acid starvation, which instead activates the Gcn2 pathway to inhibit TORC1 and induce autophagy. On the other hand, nitrogen starvation suppresses TORC1 through the combined actions of the GATOR1-Sea3 complex, the Gcn2 pathway, and the TSC complex, another conserved TORC1 inhibitor. Thus, multiple, parallel signaling pathways implement negative regulation of TORC1 to ensure proper cellular starvation responses. © Fukuda et al. 2021 Article PeerReviewed Fukuda, T. and Sofyantoro, F. and Tai, Y.T. and Chia, K.H. and Matsuda, T. and Murase, T. and Morozumi, Y. and Tatebe, H. and Kanki, T. and Shiozaki, K. (2021) Tripartite suppression of fission yeast torc1 signaling by the gator1-sea3 complex, the tsc complex, and gcn2 kinase. eLife, 10. pp. 1-22. https://www.scopus.com/inward/record.uri?eid=2-s2.0-85100975689&doi=10.7554%2feLife.60969&partnerID=40&md5=73a20683e860a8f829986171a99636f8 |
| spellingShingle | Neurosciences Fukuda, T. Sofyantoro, F. Tai, Y.T. Chia, K.H. Matsuda, T. Murase, T. Morozumi, Y. Tatebe, H. Kanki, T. Shiozaki, K. Tripartite suppression of fission yeast torc1 signaling by the gator1-sea3 complex, the tsc complex, and gcn2 kinase |
| title | Tripartite suppression of fission yeast torc1 signaling by the gator1-sea3 complex, the tsc complex, and gcn2 kinase |
| title_full | Tripartite suppression of fission yeast torc1 signaling by the gator1-sea3 complex, the tsc complex, and gcn2 kinase |
| title_fullStr | Tripartite suppression of fission yeast torc1 signaling by the gator1-sea3 complex, the tsc complex, and gcn2 kinase |
| title_full_unstemmed | Tripartite suppression of fission yeast torc1 signaling by the gator1-sea3 complex, the tsc complex, and gcn2 kinase |
| title_short | Tripartite suppression of fission yeast torc1 signaling by the gator1-sea3 complex, the tsc complex, and gcn2 kinase |
| title_sort | tripartite suppression of fission yeast torc1 signaling by the gator1 sea3 complex the tsc complex and gcn2 kinase |
| topic | Neurosciences |
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