Glucose limitation induces GCN4 translation by activation of Gcn2 protein kinase

Ruojing Yang, Sheree A. Wek, Ronald Wek

Research output: Contribution to journalArticle

119 Citations (Scopus)

Abstract

Phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF-2α) is a well-characterized mechanism regulating protein synthesis in response to environmental stresses. In the yeast Saccharomyces cerevisiae, starvation for amino acids induces phosphorylation of eIF-2α by Gcn2 protein kinase, leading to elevated translation of GCN4, a transcriptional activator of more than 50 genes. Uncharged tRNA that accumulates during amino acid limitation is proposed to activate Gcn2p by associating with Gcn2p sequences homologous to histidyl-tRNA synthetase (HisRS) enzymes. Given that eIF-2α phosphorylation in mammals is induced in response to both carbohydrate and amino acid limitations, we addressed whether activation of Gcn2p in yeast is also controlled by different nutrient deprivations. We found that starvation for glucose induces Gcn2p phosphorylation of eIF-2α and stimulates GCN4 translation. Induction of eIF-2α phosphorylation by Gcn2p during glucose limitation requires the function of the HisRS-related domain but is largely independent of the ribosome binding sequences of Gcn2p. Furthermore, Gcn20p, a factor required for Gcn2 protein kinase stimulation of GCN4 expression in response to amino acid starvation, is not essential for GCN4 translational control in response to limitation for carbohydrates. These results indicate there are differences between the mechanisms regulating Gcn2p activity in response to amino acid and carbohydrate deficiency. Gcn2p induction of GCN4 translation during carbohydrate limitation enhances storage of amino acids in the vacuoles and facilitates entry into exponential growth during a shift from low-glucose to high-glucose medium. Gcn2p function also contributes to maintenance of glycogen levels during prolonged glucose starvation, suggesting a linkage between amino acid control and glycogen metabolism.

Original languageEnglish
Pages (from-to)2706-2717
Number of pages12
JournalMolecular and Cellular Biology
Volume20
Issue number8
DOIs
StatePublished - Apr 2000

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Eukaryotic Initiation Factor-2
Protein Kinases
Amino Acids
Glucose
Starvation
Phosphorylation
Histidine-tRNA Ligase
Carbohydrates
Glycogen
Yeasts
Sequence Homology
Transfer RNA
Vacuoles
Ribosomes
Saccharomyces cerevisiae
Mammals
Maintenance
Food
Enzymes
Growth

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Glucose limitation induces GCN4 translation by activation of Gcn2 protein kinase. / Yang, Ruojing; Wek, Sheree A.; Wek, Ronald.

In: Molecular and Cellular Biology, Vol. 20, No. 8, 04.2000, p. 2706-2717.

Research output: Contribution to journalArticle

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