Regulation of starvation-and virus-induced autophagy by the eIF2α kinase signaling pathway

Z Tallóczy, W Jiang, HW Virgin IV… - Proceedings of the …, 2002 - National Acad Sciences
Z Tallóczy, W Jiang, HW Virgin IV, DA Leib, D Scheuner, RJ Kaufman, EL Eskelinen…
Proceedings of the National Academy of Sciences, 2002National Acad Sciences
The eIF2α kinases are a family of evolutionarily conserved serine/threonine kinases that
regulate stress-induced translational arrest. Here, we demonstrate that the yeast eIF2α
kinase, GCN2, the target phosphorylation site of Gcn2p, Ser-51 of eIF2α, and the eIF2α-
regulated transcriptional transactivator, GCN4, are essential for another fundamental stress
response, starvation-induced autophagy. The mammalian IFN-inducible eIF2α kinase, PKR,
rescues starvation-induced autophagy in GCN2-disrupted yeast, and pkr null and Ser-51 …
The eIF2α kinases are a family of evolutionarily conserved serine/threonine kinases that regulate stress-induced translational arrest. Here, we demonstrate that the yeast eIF2α kinase, GCN2, the target phosphorylation site of Gcn2p, Ser-51 of eIF2α, and the eIF2α-regulated transcriptional transactivator, GCN4, are essential for another fundamental stress response, starvation-induced autophagy. The mammalian IFN-inducible eIF2α kinase, PKR, rescues starvation-induced autophagy in GCN2-disrupted yeast, and pkr null and Ser-51 nonphosphorylatable mutant eIF2α murine embryonic fibroblasts are defective in autophagy triggered by herpes simplex virus infection. Furthermore, PKR and eIF2α Ser-51-dependent autophagy is antagonized by the herpes simplex virus neurovirulence protein, ICP34.5. Thus, autophagy is a novel evolutionarily conserved function of the eIF2α kinase pathway that is targeted by viral virulence gene products.
National Acad Sciences