The eIF2α/ATF4 pathway is essential for stress-induced autophagy gene expression
By Wafa B’chir, A. Maurin, Valérie Carraro, J. Averous, C. Jousse, Yuki Muranishi, Laurent Parry, G. Stepien, P. Fafournoux, A. Bruhat. Nucleic Acids Research, 2013
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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.
Subfields: Cell Biology, Epidemiology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/d3532ab91aa75af7f5099ff2199a87d823008a35
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Citations in the corpus
- ER stress: Autophagy induction, inhibition and selection (2015, background): “In addition, ATG10, GABARAP, and ATG5 transcription is followed by activation of the DDIT3 transcription factor alone.(103) Furthermore, DDIT3 can stimulate autophagosome formation through downregulation of BCL2 expression.”
- Nutrient sensing and TOR signaling in yeast and mammals (2017, positive): “…enzymes involved in amino acid metabolism (Hinnebusch & Natarajan, 2002; Siu et al , 2002; Averous et al , 2004; Hinnebusch, 2005; Kilberg et al , 2009; Staschke et al , 2010), and factors involved in autophagy (B’chir et al , 2013; Fig 2), thereby allowing adaptation to amino acid starvation.”