A stay of execution: ATF4 regulation and potential outcomes for the integrated stress response

被引：81

作者：

Neill, Graham ^{[1
]}

Masson, Glenn R. ^{[1
]}

机构：

[1] Univ Dundee, Sch Med, Div Cellular & Syst Med, Dundee, Scotland

来源：

FRONTIERS IN MOLECULAR NEUROSCIENCE | 2023年 / 16卷

关键词：

ATF4; ISR; dimerization; target genes; PTM; apoptosis; cell division; synaptic plasticity; TRANSCRIPTION FACTOR 4; ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; CELL-CYCLE PROGRESSION; ASPARAGINE SYNTHETASE GENE; ER-STRESS; DNA-BINDING; TRANSLATION INITIATION; LEUCINE-ZIPPER; MESSENGER-RNA;

D O I：

10.3389/fnmol.2023.1112253

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

ATF4 is a cellular stress induced bZIP transcription factor that is a hallmark effector of the integrated stress response. The integrated stress response is triggered by phosphorylation of the alpha subunit of the eukaryotic initiation factor 2 complex that can be carried out by the cellular stress responsive kinases; GCN2, PERK, PKR, and HRI. eIF2 alpha phosphorylation downregulates mRNA translation initiation en masse, however ATF4 translation is upregulated. The integrated stress response can output two contradicting outcomes in cells; pro-survival or apoptosis. The mechanism for choice between these outcomes is unknown, however combinations of ATF4 heterodimerisation partners and post-translational modifications have been linked to this regulation. This semi-systematic review article covers ATF4 target genes, heterodimerisation partners and post-translational modifications. Together, this review aims to be a useful resource to elucidate the mechanisms controlling the effects of the integrated stress response. Additional putative roles of the ATF4 protein in cell division and synaptic plasticity are outlined.

引用

页数：14

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