GCN2 (encoded in humans by the gene EIF2AK4) is activated as a result of amino acid deprivation. The mechanisms regarding this activation are still being researched; however, one mechanism has been studied in yeast. It was observed that GCN2 binds to uncharged/deacylated tRNA which causes a conformational change, resulting in dimerization. Dimerization then causes autophosphorylation and activation. Other stressors have also been reported to activate GCN2. GCN2 activation was observed in glucose deprived tumor cells, although it was suggested that it was an indirect effect due to cells using amino acids as an alternate energy source. In mouse embryonic fibroblast cells and human keratinocytes, GCN2 was activated due to UV light exposure. The pathways for this activation require further research, although multiple models have been proposed, including crosslinking between GCN2 and tRNA.