Overview:

GCN2, or general control nonderepressible 2, is a conserved serine/threonine protein kinase crucial for cellular responses to amino acid deprivation. Activated by uncharged tRNAs during amino acid starvation, GCN2 phosphorylates eukaryotic initiation factor 2α (eIF2α), globally inhibiting protein synthesis and selectively translating mRNAs like ATF4. This pathway, identified in yeast and conserved in mammals, plays roles in immune responses, metabolic homeostasis, and the integrated stress response (ISR). Dysregulation of GCN2 is implicated in diseases, including metabolic disorders. The pathway's evolutionary conservation underscores its fundamental role in cellular stress responses.

Genbank Number:

NM_001013703

References:

1. Hinnebusch AG. Annu Rev Microbiol. 2005;59:407-450.
2. Wek RC et al. Biochem Soc Trans. 2006;34(Pt 1):7-11.
3. Harding HP et al. Nature. 1999;397(6716):271-274.
4. Zaborske JM et al. J Biol Chem. 2009;284(37):25254-25267.