期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 280, 期 17, 页码 16925-16933出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M412882200
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资金
- NIAID NIH HHS [R56 AI033600] Funding Source: Medline
- NIDDK NIH HHS [R01 DK 16272, R01 DK42394, R01 DK016272] Funding Source: Medline
Exposure to arsenite inhibits protein synthesis and activates multiple stress signaling pathways. Although arsenite has diverse effects on cell metabolism, we demonstrated that phosphorylation of eukaryotic translation initiation factor 2 at Ser-51 on the alpha subunit was necessary to inhibit protein synthesis initiation in arsenite-treated cells and was essential for stress granule formation. Of the four protein kinases known to phosphorylate eukaryotic translation initiation factor 2 alpha, only the heme-regulated inhibitor kinase (HRI) was required for the translational inhibition in response to arsenite treatment in mouse embryonic fibroblasts. In addition, HRI expression was required for stress granule formation and cellular survival after arsenite treatment. In vivo studies elucidated a fundamental requirement for HRI in murine survival upon acute arsenite exposure. The results demonstrated an essential role for HRI in mediating arsenite stress-induced phosphorylation of eukaryotic translation initiation factor 2 alpha, inhibition of protein synthesis, stress granule formation, and survival.
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