eIF4A inactivates TORC1 in response to amino acid starvation.

Autor: Tsokanos FF; Division of Signal Transduction in Cancer and Metabolism, German Cancer Research Center (DKFZ), Heidelberg, Germany., Albert MA; Division of Signal Transduction in Cancer and Metabolism, German Cancer Research Center (DKFZ), Heidelberg, Germany., Demetriades C; Division of Signal Transduction in Cancer and Metabolism, German Cancer Research Center (DKFZ), Heidelberg, Germany., Spirohn K; Department of Cell and Molecular Biology, Medical Faculty Mannheim, German Cancer Research Center (DKFZ), Division of Signaling and Functional Genomics and Heidelberg University, Heidelberg, Germany., Boutros M; Department of Cell and Molecular Biology, Medical Faculty Mannheim, German Cancer Research Center (DKFZ), Division of Signaling and Functional Genomics and Heidelberg University, Heidelberg, Germany., Teleman AA; Division of Signal Transduction in Cancer and Metabolism, German Cancer Research Center (DKFZ), Heidelberg, Germany a.teleman@dkfz.de.
Jazyk: angličtina
Zdroj: The EMBO journal [EMBO J] 2016 May 17; Vol. 35 (10), pp. 1058-76. Date of Electronic Publication: 2016 Mar 17.
DOI: 10.15252/embj.201593118
Abstrakt: Amino acids regulate TOR complex 1 (TORC1) via two counteracting mechanisms, one activating and one inactivating. The presence of amino acids causes TORC1 recruitment to lysosomes where TORC1 is activated by binding Rheb. How the absence of amino acids inactivates TORC1 is less well understood. Amino acid starvation recruits the TSC1/TSC2 complex to the vicinity of TORC1 to inhibit Rheb; however, the upstream mechanisms regulating TSC2 are not known. We identify here the eIF4A-containing eIF4F translation initiation complex as an upstream regulator of TSC2 in response to amino acid withdrawal in Drosophila We find that TORC1 and translation preinitiation complexes bind each other. Cells lacking eIF4F components retain elevated TORC1 activity upon amino acid removal. This effect is specific for eIF4F and not a general consequence of blocked translation. This study identifies specific components of the translation machinery as important mediators of TORC1 inactivation upon amino acid removal.
(© 2016 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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