Stress-induced inhibition of translation independently of eIF2α phosphorylation.
Exposure of fission yeast cells to ultraviolet (UV) light leads to inhibition of translation and phosphorylation of the eukaryotic initiation factor-2α (eIF2α). This phosphorylation is a common response to stress in all eukaryotes. It leads to inhibition of translation at the initiation stage and is thought to be the main reason why stressed cells dramatically reduce protein synthesis. Phosphorylation of eIF2α has been taken as a readout for downregulation of translation, but the role of eIF2α phosphorylation in the downregulation of general translation has not been much investigated. We show here that UV-induced global inhibition of translation in fission yeast cells is independent of eIF2α phosphorylation and the eIF2α kinase general control nonderepressible-2 protein (Gcn2). Also, in budding yeast and mammalian cells, the UV-induced translational depression is largely independent of GCN2 and eIF2α phosphorylation. Furthermore, exposure of fission yeast cells to oxidative stress generated by hydrogen peroxide induced an inhibition of translation that is also independent of Gcn2 and of eIF2α phosphorylation. Our findings show that stress-induced translational inhibition occurs through an unknown mechanism that is likely to be conserved through evolution.
Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
Jon Halvor Jonsrud
JH
Knutsen
Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
Gro Elise
GE
Rødland
Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
Cathrine Arnason
CA
Bøe
Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
Tine Weise
TW
Håland
Department of Chemistry & Molecular Biology, University of Gothenburg, Gothenburg, Sweden.
Per
P
Sunnerhagen
Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway beata.grallert@rr-research.no eboye@rr-research.no.
Beáta
B
Grallert
Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway beata.grallert@rr-research.no eboye@rr-research.no.
Erik
E
Boye
D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000235:genetics / Q000528:radiation effects; D014176:Protein Biosynthesis / Q000528:radiation effects*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological / Q000235:genetics / Q000528:radiation effects*; D014466:Ultraviolet Rays
D015852:Eukaryotic Initiation Factor-2; D029702:Schizosaccharomyces pombe Proteins; C539007:Gcn2 protein, S pombe; D017346:Protein Serine-Threonine Kinases
EIF2S1; SPBC4B4.04; SUI2; Stress; Translation; Ultraviolet light; eIF2α