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

被引：875

作者：

B'chir, Wafa ^{[1
,2
]}

Maurin, Anne-Catherine ^{[1
,2
]}

Carraro, Valerie ^{[1
,2
]}

Averous, Julien ^{[1
,2
]}

Jousse, Celine ^{[1
,2
]}

Muranishi, Yuki ^{[1
,2
]}

Parry, Laurent ^{[1
,2
]}

Stepien, Georges ^{[1
,2
]}

Fafournoux, Pierre ^{[1
,2
]}

Bruhat, Alain ^{[1
,2
]}

机构：

[1] INRA, UMR Nutr Humaine 1019, Ctr Clermont Ferrand Theix, F-63122 St Genes Champanelle, France

[2] Univ Clermont 1, UMR Nutr Humaine 1019, UFR Med, Clermont Ferrand, France

来源：

NUCLEIC ACIDS RESEARCH | 2013年 / 41卷 / 16期

关键词：

ENDOPLASMIC-RETICULUM STRESS; AMINO-ACID DEPRIVATION; ASPARAGINE SYNTHETASE GENE; UNFOLDED PROTEIN RESPONSE; TRANSLATIONAL CONTROL; MOLECULAR-MECHANISMS; CELL-SURVIVAL; TRANSCRIPTION FACTORS; HISTONE ACETYLATION; OXIDATIVE STRESS;

D O I：

10.1093/nar/gkt563

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In response to different environmental stresses, eIF2 alpha 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 eIF2 alpha/ATF4 pathway directs an autophagy gene transcriptional program in response to amino acid starvation or endoplasmic reticulum stress. The eIF2 alpha-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 eIF2 alpha-ATF4 pathway in the fine-tuning of the autophagy gene transcription program in response to stresses.

引用

页码：7683 / 7699

页数：17

共 69 条

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