Elongation factor 2 kinase promotes cell survival by inhibiting protein synthesis without inducing autophagy.

Cellular Signalling
Claire E MooreChristopher G Proud

Abstract

Eukaryotic elongation factor 2 kinase (eEF2K) inhibits the elongation stage of protein synthesis by phosphorylating its only known substrate, eEF2. eEF2K is tightly regulated by nutrient-sensitive signalling pathways. For example, it is inhibited by signalling through mammalian target of rapamycin complex 1 (mTORC1). It is therefore activated under conditions of nutrient deficiency. Here we show that inhibiting eEF2K or knocking down its expression renders cancer cells sensitive to death under nutrient-starved conditions, and that this is rescued by compounds that block protein synthesis. This implies that eEF2K protects nutrient-deprived cells by inhibiting protein synthesis. Cells in which signalling through mTORC1 is highly active are very sensitive to nutrient withdrawal. Inhibiting mTORC1 protects them. Our data reveal that eEF2K makes a substantial contribution to the cytoprotective effect of mTORC1 inhibition. eEF2K is also reported to promote another potentially cytoprotective process, autophagy. We have used several approaches to test whether inhibition or loss of eEF2K affects autophagy under a variety of conditions. We find no evidence that eEF2K is involved in the activation of autophagy in the cell types we have st...Continue Reading

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Citations

Mar 16, 2016·Cellular Signalling·Andreas Mæchel FritzenBente Kiens
Jan 3, 2018·The Journal of Pathology·Amal M El-Naggar, Poul H Sorensen
May 8, 2020·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Didem Karakas, Bulent Ozpolat
Dec 14, 2017·International Journal of Cancer. Journal International Du Cancer·Jianling XieChristopher G Proud
Feb 10, 2019·Apoptosis : an International Journal on Programmed Cell Death·Satoshi KameshimaHideyuki Yamawaki
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Mar 30, 2021·The Biochemical Journal·Roman V LenchineChristopher G Proud
Aug 6, 2021·Pathology, Research and Practice·Mingxia JiangChengxin Song

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Datasets Mentioned

BETA
GE27-4577-01

Methods Mentioned

BETA
transfection
lipidation

Software Mentioned

Leica Application Suite X ( LAS X )
GraphPAD Prism

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