Phosphorylation of initiation factor 2α by protein kinase GCN2 mediates gene-specific translational control of GCN4 in yeast

Thomas E. Dever, Lan Feng, Ronald C. Wek, A. Mark Cigan, Thomas F. Donahue, Alan G. Hinnebusch

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Abstract

We show that phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF-2) by the protein kinase GCN2 mediates translational control of the yeast transcriptional activator GCN4. In vitro, GCN2 specifically phosphorylates the α subunit of rabbit or yeast eIF-2. In vivo, phosphorylation of eIF-2α increases in response to amino acid starvation, which is dependent on GCN2. Substitution of Ser-51 with alanine eliminates phosphorylation of eIF-2α by GCN2 in vivo and in vitro and abolishes increased expression of GCN4 and amino acid biosynthetic genes under its control in amino acid-starved cells. The Asp-51 substitution mimics the phosphorylated state and derepresses GCN4 in the absence of GCN2. Thus, an established mechanism for regulating total protein synthesis in mammalian cells mediates gene-specific translational control in yeast.

Original languageEnglish (US)
Pages (from-to)585-596
Number of pages12
JournalCell
Volume68
Issue number3
DOIs
StatePublished - Feb 7 1992

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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