The EIF2α/ATF4 Pathway is Essential for Stress-induced Autophagy Gene Expression

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2013 Jun 28

PMID 23804767

Citations 560

Authors

Wafa Bchir

Anne-Catherine Maurin

Valerie Carraro

Julien Averous

Celine Jousse

Yuki Muranishi

Laurent Parry

Georges Stepien

Pierre Fafournoux

Alain Bruhat

Affiliations

Soon will be listed here.

Abstract

In response to different environmental stresses, eIF2α phosphorylation represses global translation coincident with preferential translation of ATF4, a master regulator controlling the transcription of key genes essential for adaptative functions. Here, we establish that the eIF2α/ATF4 pathway directs an autophagy gene transcriptional program in response to amino acid starvation or endoplasmic reticulum stress. The eIF2α-kinases GCN2 and PERK and the transcription factors ATF4 and CHOP are also required to increase the transcription of a set of genes implicated in the formation, elongation and function of the autophagosome. We also identify three classes of autophagy genes according to their dependence on ATF4 and CHOP and the binding of these factors to specific promoter cis elements. Furthermore, different combinations of CHOP and ATF4 bindings to target promoters allow the trigger of a differential transcriptional response according to the stress intensity. Overall, this study reveals a novel regulatory role of the eIF2α-ATF4 pathway in the fine-tuning of the autophagy gene transcription program in response to stresses.

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