A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Regulation of starvation- and virus-induced autophagy by the eIF2 alpha kinase signaling pathway
Tekijät: Talloczy Z, Jiang WX, Virgin HW, Leib DA, Scheuner D, Kaufman RJ, Eskelinen EL, Levine B
Kustantaja: NATL ACAD SCIENCES
Julkaisuvuosi: 2002
Lehti:Proceedings of the National Academy of Sciences of the United States of America
Tietokannassa oleva lehden nimiPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Lehden akronyymi: P NATL ACAD SCI USA
Vuosikerta: 99
Numero: 1
Aloitussivu: 190
Lopetussivu: 195
Sivujen määrä: 6
ISSN: 0027-8424
DOI: https://doi.org/10.1073/pnas.012485299
Tiivistelmä
The eIF2alpha kinases are a family of evolutionarily conserved serine/threonine kinases that regulate stress-induced translational arrest. Here, we demonstrate that the yeast eIF2alpha kinase, GCN2, the target phosphorylation site of Gcn2p, Ser-51 of eIF2alpha, and the eIF2alpha-regulated transcriptional transactivator, GCN4, are essential for another fundamental stress response, starvation-induced autophagy. The mammalian IFN-inducible eIF2alpha kinase, PKR, rescues starvation-induced autophagy in GCN2-disrupted yeast, and pkr null and Ser-51 nonphosphorylatable mutant eIF2alpha murine embryonic fibroblasts are defective in autophagy triggered by herpes simplex virus infection. Furthermore, PKR and eIF2alpha 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 eIF2alpha kinase pathway that is targeted by viral virulence gene products.
The eIF2alpha kinases are a family of evolutionarily conserved serine/threonine kinases that regulate stress-induced translational arrest. Here, we demonstrate that the yeast eIF2alpha kinase, GCN2, the target phosphorylation site of Gcn2p, Ser-51 of eIF2alpha, and the eIF2alpha-regulated transcriptional transactivator, GCN4, are essential for another fundamental stress response, starvation-induced autophagy. The mammalian IFN-inducible eIF2alpha kinase, PKR, rescues starvation-induced autophagy in GCN2-disrupted yeast, and pkr null and Ser-51 nonphosphorylatable mutant eIF2alpha murine embryonic fibroblasts are defective in autophagy triggered by herpes simplex virus infection. Furthermore, PKR and eIF2alpha 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 eIF2alpha kinase pathway that is targeted by viral virulence gene products.
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