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 journalArticle

535 Citations (Scopus)

Abstract

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
Volume99
Issue number1
DOIs
StatePublished - Jan 8 2002

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Autophagy
Starvation
Phosphotransferases
Viruses
Simplexvirus
Yeasts
Trans-Activators
Protein-Serine-Threonine Kinases
Viral Proteins
Virus Diseases
Virulence
Fibroblasts
Phosphorylation
Proteins

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Regulation of starvation- and virus-induced autophagy by the elF2α kinase signaling pathway. / Tallóczy, Zsolt; Jiang, Wenxia; Virgin IV, Herbert W.; Leib, David A.; Scheuner, Donalyn; Kaufman, Randal J.; Eskelinen, Eeva Liisa; Levine, Beth.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 1, 08.01.2002, p. 190-195.

Research output: Contribution to journalArticle

Tallóczy, Zsolt ; Jiang, Wenxia ; Virgin IV, Herbert W. ; Leib, David A. ; Scheuner, Donalyn ; Kaufman, Randal J. ; Eskelinen, Eeva Liisa ; Levine, Beth. / Regulation of starvation- and virus-induced autophagy by the elF2α kinase signaling pathway. In: Proceedings of the National Academy of Sciences of the United States of America. 2002 ; Vol. 99, No. 1. pp. 190-195.
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