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 language | English |
|---|---|
| Article number | 1112253 |
| Number of pages | 14 |
| Journal | Frontiers in Molecular Neuroscience |
| Volume | 16 |
| Early online date | 7 Feb 2023 |
| DOIs | |
| Publication status | E-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