TY - JOUR
T1 - Regulation of starvation- and virus-induced autophagy by the elF2α kinase signaling pathway
AU - Tallóczy, Zsolt
AU - Jiang, Wenxia
AU - Virgin IV, Herbert W.
AU - Leib, David A.
AU - Scheuner, Donalyn
AU - Kaufman, Randal J.
AU - Eskelinen, Eeva Liisa
AU - Levine, Beth
PY - 2002/1/8
Y1 - 2002/1/8
N2 - The elF2α kinases are a family of evolutionarily conserved serine/threonine kinases that regulate stress-induced translational arrest. Here, we demonstrate that the yeast elF2α kinase, GCN2, the target phosphorylation site of Gcn2p, Ser-51 of elF2α, and the elF2α-regulated transcriptional transactivator, GCN4, are essential for another fundamental stress response, starvation-induced autophagy. The mammalian IFN-inducible elF2α kinase, PKR, rescues starvationinduced autophagy in GCN2-disrupted yeast, and pkr null and Set-51 nonphosphorylatable mutant elF2α murine embryonic fibroblasts are defective in autophagy triggered by herpes simplex virus infection. Furthermore, PKR and elF2α 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 elF2α kinase pathway that is targeted by viral virulence gene products.
AB - The elF2α kinases are a family of evolutionarily conserved serine/threonine kinases that regulate stress-induced translational arrest. Here, we demonstrate that the yeast elF2α kinase, GCN2, the target phosphorylation site of Gcn2p, Ser-51 of elF2α, and the elF2α-regulated transcriptional transactivator, GCN4, are essential for another fundamental stress response, starvation-induced autophagy. The mammalian IFN-inducible elF2α kinase, PKR, rescues starvationinduced autophagy in GCN2-disrupted yeast, and pkr null and Set-51 nonphosphorylatable mutant elF2α murine embryonic fibroblasts are defective in autophagy triggered by herpes simplex virus infection. Furthermore, PKR and elF2α 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 elF2α kinase pathway that is targeted by viral virulence gene products.
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U2 - 10.1073/pnas.012485299
DO - 10.1073/pnas.012485299
M3 - Article
C2 - 11756670
AN - SCOPUS:0037039442
SN - 0027-8424
VL - 99
SP - 190
EP - 195
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 1
ER -