Regulation of Starvation- and Virus-induced Autophagy by the EIF2alpha Kinase Signaling Pathway

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2002 Jan 5

PMID 11756670

Citations 363

Authors

Zsolt Talloczy

Wenxia Jiang

Herbert W Virgin 4th

David A Leib

Donalyn Scheuner

Randal J Kaufman

Eeva-Liisa Eskelinen

Beth Levine

Affiliations

Soon will be listed here.

Abstract

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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