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Hsp90 binds and regulates Gcn2, the ligand-inducible kinase of the alpha subunit of eukaryotic translation initiation factor 2 [corrected]

Contributeurs/tricesDonze, Olivier; Picard, Didierorcid
Publié dansMolecular and cellular biology, vol. 19, no. 12, p. 8422-8432
Date de publication1999
Résumé

The protein kinase Gcn2 stimulates translation of the yeast transcription factor Gcn4 upon amino acid starvation. Using genetic and biochemical approaches, we show that Gcn2 is regulated by the molecular chaperone Hsp90 in budding yeast Saccharomyces cerevisiae. Specifically, we found that (i) several Hsp90 mutant strains exhibit constitutive expression of a GCN4-lacZ reporter plasmid; (ii) Gcn2 and Hsp90 form a complex in vitro as well as in vivo; (iii) the specific inhibitors of Hsp90, geldanamycin and macbecin I, enhance the association of Gcn2 with Hsp90 and inhibit its kinase activity in vitro; (iv) in vivo, macbecin I strongly reduces the levels of Gcn2; (v) in a strain expressing the temperature-sensitive Hsp90 mutant G170D, both the accumulation and activity of Gcn2 are abolished at the restrictive temperature; and (vi) the Hsp90 cochaperones Cdc37, Sti1, and Sba1 are required for the response to amino acid starvation. Taken together, these data identify Gcn2 as a novel target for Hsp90, which plays a crucial role for the maturation and regulation of Gcn2.

Mots-clés
  • 5' Untranslated Regions
  • Benzoquinones
  • Cell Cycle Proteins/metabolism
  • Chaperonins
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Fungal Proteins/genetics/metabolism
  • Gene Expression
  • HSP90 Heat-Shock Proteins/antagonists & inhibitors/genetics/metabolism
  • Heat-Shock Proteins/genetics/metabolism
  • Humans
  • Lac Operon
  • Lactams, Macrocyclic
  • Ligands
  • Molecular Chaperones/metabolism
  • Mutagenesis
  • Peptide Initiation Factors/genetics/metabolism
  • Protein Biosynthesis
  • Protein Kinases/genetics/metabolism
  • Quinones
  • RNA, Messenger
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
Citation (format ISO)
DONZE, Olivier, PICARD, Didier. Hsp90 binds and regulates Gcn2, the ligand-inducible kinase of the alpha subunit of eukaryotic translation initiation factor 2 [corrected]. In: Molecular and cellular biology, 1999, vol. 19, n° 12, p. 8422–8432.
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Article (Published version)
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Identifiants
ISSN du journal0270-7306
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Création01/12/2009 11:16:00
Première validation01/12/2009 11:16:00
Heure de mise à jour14/03/2023 15:18:57
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