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

Abstract	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.
Authors	O Donzé, D Picard
Journal	Molecular and cellular biology (Mol Cell Biol) Vol. 19 Issue 12 Pg. 8422-32 (Dec 1999) ISSN: 0270-7306 [Print] United States
PMID	10567567 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	5' Untranslated Regions Benzoquinones CDC37 protein, S cerevisiae CDC37 protein, human Cell Cycle Proteins DNA-Binding Proteins Drosophila Proteins Fungal Proteins HSP82 protein, S cerevisiae HSP90 Heat-Shock Proteins Heat-Shock Proteins Lactams, Macrocyclic Ligands Molecular Chaperones Peptide Initiation Factors Quinones RNA, Messenger SBA1 protein, S cerevisiae STI1 protein, S cerevisiae Saccharomyces cerevisiae Proteins macbecin I Protein Kinases Chaperonins geldanamycin
Topics	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

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