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Signaling plasticity in the integrated stress response

Authors :
Morgane Boone
Francesca Zappa
Source :
Frontiers in Cell and Developmental Biology, Vol 11 (2023)
Publication Year :
2023
Publisher :
Frontiers Media S.A., 2023.

Abstract

The Integrated Stress Response (ISR) is an essential homeostatic signaling network that controls the cell’s biosynthetic capacity. Four ISR sensor kinases detect multiple stressors and relay this information to downstream effectors by phosphorylating a common node: the alpha subunit of the eukaryotic initiation factor eIF2. As a result, general protein synthesis is repressed while select transcripts are preferentially translated, thus remodeling the proteome and transcriptome. Mounting evidence supports a view of the ISR as a dynamic signaling network with multiple modulators and feedback regulatory features that vary across cell and tissue types. Here, we discuss updated views on ISR sensor kinase mechanisms, how the subcellular localization of ISR components impacts signaling, and highlight ISR signaling differences across cells and tissues. Finally, we consider crosstalk between the ISR and other signaling pathways as a determinant of cell health.

Details

Language :
English
ISSN :
2296634X
Volume :
11
Database :
Directory of Open Access Journals
Journal :
Frontiers in Cell and Developmental Biology
Publication Type :
Academic Journal
Accession number :
edsdoj.01a07505a54b4cd68361c1422e49e91e
Document Type :
article
Full Text :
https://doi.org/10.3389/fcell.2023.1271141