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Cited by 1,162Endoplasmic Reticulum Stress and DiseaseAutophagy in Disease and TherapyRNA and protein synthesis mechanisms

The eIF2α/ATF4 pathway is essential for stress-induced autophagy gene expression

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B’chir, Wafa, Maurin, Anne-Catherine, Carraro, Valérie, Averous, Julien, Jousse, Céline, Muranishi, Yuki, Parry, Laurent, Stepien, Georges +2 more·2013·Nucleic Acids Research
DOI 10.1093/nar/gkt563PMC PMC3763548
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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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Crossref · 10.1093/nar/gkt563

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  • The authors identified 20 targets related to autophagy activation and validated them by qPCR: ATG10, ATG14, ATG16L1, ATG3, ATG4, ATG7, ATG9A, BCL2, GABARAP, GABARAPL1, MAP1LC3B, NBR1, OPTN, PINK1, SQSTM1, ULK1, ULK2, UVRAG, WDR45, WIPI1.

    “In a first case, starting from experimental data available in the literature, we identified 20 targets related to autophagy activation and validated them by qPCR: ATG10, ATG14, ATG16L1, ATG3, ATG4, ATG7, ATG9A, BCL2, GABARAP, GABARAPL1, MAP1LC3B, NBR1, OPTN, PINK1, SQSTM1, ULK1, ULK2, UVRAG, WDR45, WIPI1 (Fig. 2) [18–27].”

    From A gene toolbox for monitoring autophagy transcription (2021) · cites this paper as [21]

    The Materials and Methods section (page unavailable) identifies several genes in the cited list as autophagy genes, including Atg10, Atg7, Gabarap, Map1lc3b, Nbr1 and Sqstm1. It does not identify the full set of 20. In the citing sentence, “we identified” and “validated them by qPCR” describe the citing authors’ work, not a result attributed to this source. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • The activation list was derived from comparison of publications reporting conditions of gene up-regulation upon autophagy activation.

    “A so called “activation list” has been derived from the comparison of publications, in which we reported conditions of gene up-regulation upon autophagy activation [18–27].”

    From A gene toolbox for monitoring autophagy transcription (2021) · cites this paper as [21]

  • The restricted "induction list" for the prediction of autophagy activation state is made of 20 targets and was obtained by combining data from previous publications documenting increased mRNA expression following autophagy induction.

    “The restricted “induction list” for the prediction of autophagy activation state, made by 20 targets, was obtained combining data from previous publications [18–27], in which have been documented the increase of the mRNA expression following autophagy induction.”

    From A gene toolbox for monitoring autophagy transcription (2021) · cites this paper as [21]

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Authors
B’chir, W., Maurin, A.-C., Carraro, V., Averous, J., Jousse, C., Muranishi, Y., Parry, L., Stepien, G., Fafournoux, P., & Bruhat, A.
Affiliations
Unité de Nutrition Humaine (FR)
Corresponding author
Bruhat, Alain
ORCID
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2013-06-25
Volume
41
Issue
16
Pages
7683-7699
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/gkt563
PMC
PMC3763548
OpenAlex
W2048098925
Cited by
1,162
References
5
Citations by year
2026: 92 · 2025: 98 · 2024: 106 · 2023: 116 · 2022: 112 · 2021: 120 · 2020: 110 · 2019: 80 · 2018: 94 · 2017: 83 · 2016: 59 · 2015: 48 · 2014: 37 · 2013: 6
FWCI
29.20
Type
journal article
Language
en
Open access
Licence
Locations
  • Nucleic Acids Research (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by-nc)
  • HAL (submittedVersion)
Funders
  • Fondation ARC pour la Recherche sur le Cancer
  • Institut National de la Recherche Agronomique
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords
amino acid starvation, endoplasmic reticulum stress, GCN2, PERK, CHOP, ATF4, autophagosome formation, promoter cis-acting elements, stress response, translation repression
MeSH terms
Sequestosome-1 Protein, Amino Acids, Animals, Autophagy, Cells, Cultured, Heat-Shock Proteins, Transcriptional Activation, Eukaryotic Initiation Factor-2, Up-Regulation, Protein Serine-Threonine Kinases, eIF-2 Kinase, Response Elements, Adaptor Proteins, Signal Transducing, Mice, Activating Transcription Factor 4, Transcription Factor CHOP, Endoplasmic Reticulum Stress

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