GCN2-Mediated eIF2α Phosphorylation Is Required for Central Nervous System Remyelination.

ABSTRACT: Under conditions of amino acid deficiency, mammalian cells activate a nutrient-sensing kinase known as general control nonderepressible 2 (GCN2). The activation of GCN2 results in the phosphorylation of the alpha subunit of the eukaryotic initiation factor 2 (eIF2α), which can be phosphorylated by three other three integrated stress response (ISR) kinases, reducing overall protein synthesis. GCN2 activation also promotes the translation of specific mRNAs, some of which encode transcription factors that enhance the transcription of genes involved in the synthesis, transport, and metabolism of amino acids to restore cellular homeostasis. The phosphorylation of eIF2α has been shown to protect oligodendrocytes, the cells responsible for producing myelin in the central nervous system during rem

SUBMITTER: Falcon P 

PROVIDER: S-EPMC11855834 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature