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

Graham Neill, Glenn Masson (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)
151 Downloads (Pure)

Abstract

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. eIF2α 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.
Original languageEnglish
Article number1112253
Number of pages14
JournalFrontiers in Molecular Neuroscience
Volume16
Early online date7 Feb 2023
DOIs
Publication statusE-pub ahead of print - 7 Feb 2023

Keywords

  • ATF4
  • ISR
  • PTM
  • apoptosis
  • cell division
  • dimerization
  • synaptic plasticity
  • target genes

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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