Leucyl-tRNA Synthetase Controls TORC1 via the EGO Complex

被引：274

作者：

Bonfils, Gregory ^{[1
]}

Jaquenoud, Malika ^{[1
]}

Bontron, Severine ^{[1
]}

Ostrowicz, Clemens ^{[2
]}

Ungermann, Christian ^{[2
]}

De Virgilio, Claudio ^{[1
]}

机构：

[1] Univ Fribourg, Dept Biol, Div Biochem, CH-1700 Fribourg, Switzerland

[2] Univ Osnabruck, Biochem Sect, Dept Biol & Chem, D-49076 Osnabruck, Germany

来源：

MOLECULAR CELL | 2012年 / 46卷 / 01期

基金：

瑞士国家科学基金会;

关键词：

AMINO-ACID; SACCHAROMYCES-CEREVISIAE; RAG GTPASES; YEAST; TARGET; MTORC1; ACTIVATION; EXPRESSION; GROWTH; CANCER;

D O I：

10.1016/j.molcel.2012.02.009

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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..

引用

页码：105 / 110

页数：6

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