Phosphorylation of eukaryotic initiation factor-2α (eIF2α) in autophagy.

Cell Death & Disease
Juliette HumeauGuido Kroemer

Abstract

The integrated stress response is characterized by the phosphorylation of eukaryotic initiation factor-2α (eIF2α) on serine 51 by one out of four specific kinases (EIF2AK1 to 4). Here we provide three series of evidence suggesting that macroautophagy (to which we refer to as autophagy) induced by a variety of distinct pharmacological agents generally requires this phosphorylation event. First, the induction of autophagic puncta by various distinct compounds was accompanied by eIF2α phosphorylation on serine 51. Second, the modulation of autophagy by >30 chemically unrelated agents was partially inhibited in cells expressing a non-phosphorylable (S51A) mutant of eIF2α or lacking all four eIF2α kinases, although distinct kinases were involved in the response to different autophagy inducers. Third, inhibition of eIF2α phosphatases was sufficient to stimulate autophagy. In synthesis, it appears that eIF2α phosphorylation is a central event for the stimulation of autophagy.

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Citations

Sep 19, 2020·Molecular & Cellular Oncology·Juliette HumeauGuido Kroemer
Sep 15, 2020·Oncoimmunology·Juliette HumeauGuido Kroemer
Sep 25, 2020·Scandinavian Journal of Immunology·Inger Øynebråten
Nov 11, 2020·The Journal of Biological Chemistry·Tapas MukherjeeStephen E Girardin
Dec 19, 2020·Cell Death and Differentiation·Giulia CerratoGuido Kroemer
Jan 8, 2021·The Journal of Biological Chemistry·Tapas MukherjeeStephen E Girardin
Mar 23, 2021·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Koffi L LakpaJonathan D Geiger

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Methods Mentioned

BETA
fluorescence microscopy
flow cytometry
genetic modification
Protein Assay
electrophoresis

Software Mentioned

R
stats R
ggpubr R package

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