Signaling plasticity in the integrated stress response

Autor: Morgane Boone, Francesca Zappa
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Frontiers in Cell and Developmental Biology, Vol 11 (2023)
Druh dokumentu: article
ISSN: 2296-634X
DOI: 10.3389/fcell.2023.1271141
Popis: 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.
Databáze: Directory of Open Access Journals