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eIF 4A inactivates TORC 1 in response to amino acid starvation
Author(s) -
Tsokanos FoivosFilippos,
Albert MarieAstrid,
Demetriades Constantinos,
Spirohn Kerstin,
Boutros Michael,
Teleman Aurelio A
Publication year - 2016
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201593118
Subject(s) - rheb , biology , amino acid , translation (biology) , microbiology and biotechnology , biochemistry , tsc1 , mtorc1 , eukaryotic translation , phosphorylation , signal transduction , pi3k/akt/mtor pathway , messenger rna , gene , protein kinase b
Amino acids regulate TOR complex 1 ( TORC 1) via two counteracting mechanisms, one activating and one inactivating. The presence of amino acids causes TORC 1 recruitment to lysosomes where TORC 1 is activated by binding Rheb. How the absence of amino acids inactivates TORC 1 is less well understood. Amino acid starvation recruits the TSC 1/ TSC 2 complex to the vicinity of TORC 1 to inhibit Rheb; however, the upstream mechanisms regulating TSC 2 are not known. We identify here the eIF 4A‐containing eIF 4F translation initiation complex as an upstream regulator of TSC 2 in response to amino acid withdrawal in Drosophila . We find that TORC 1 and translation preinitiation complexes bind each other. Cells lacking eIF 4F components retain elevated TORC 1 activity upon amino acid removal. This effect is specific for eIF 4F and not a general consequence of blocked translation. This study identifies specific components of the translation machinery as important mediators of TORC 1 inactivation upon amino acid removal.