Regulation of starvation- and virus-induced autophagy by the elF2α kinase signaling pathway

Zsolt Tallóczy, Wenxia Jiang, Herbert W. Virgin IV, David A. Leib, Donalyn Scheuner, Randal J. Kaufman, Eeva Liisa Eskelinen, Beth Levine

Research output: Contribution to journalArticlepeer-review

656 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)190-195
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number1
StatePublished - Jan 8 2002

ASJC Scopus subject areas

  • General


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