Leucyl-tRNA Synthetase Controls TORC1 via the EGO Complex
Autor(en): | Bonfils, Gregory Jaquenoud, Malika Bontron, Severine Ostrowicz, Clemens Ungermann, Christian De Virgilio, Claudio |
Stichwörter: | ACTIVATION; AMINO-ACID; Biochemistry & Molecular Biology; CANCER; Cell Biology; EXPRESSION; GROWTH; MTORC1; RAG GTPASES; SACCHAROMYCES-CEREVISIAE; TARGET; YEAST | Erscheinungsdatum: | 2012 | Herausgeber: | CELL PRESS | Journal: | MOLECULAR CELL | Volumen: | 46 | Ausgabe: | 1 | Startseite: | 105 | Seitenende: | 110 | Zusammenfassung: | The target of rapamycin complex 1 (TORC1) is an essential regulator of eukaryotic cell growth that responds to growth factors, energy levels, and amino acids. The mechanisms through which the preeminent amino acid leucine signals to the TORC1-regulatory Rag GTPases, which activate TORC1 within the yeast EGO complex (EGOC) or the structurally related mammalian Rag-Ragulator complex, remain elusive. We find that the leucyl-tRNA synthetase (LeuRS) Cdc60 interacts with the Rag GTPase Gtr1 of the EGOC in a leucine-dependent manner. This interaction is necessary and sufficient to mediate leucine signaling to TORC1 and is disrupted by the engagement of Cdc60 in editing mischarged tRNA(Leu). Thus, the EGOC-TORC1 signaling module samples, via the LeuRS-intrinsic editing domain, the fidelity of tRNA(Leu) aminoacylation as a proxy for leucine availability.. |
ISSN: | 10972765 | DOI: | 10.1016/j.molcel.2012.02.009 |
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geprüft am 29.05.2024