The molecular chaperone Hsp90 plays a role in the assembly and maintenance of the 26S proteasome

• Published in: The EMBO journal Vol. 22; no. 14; pp. 3557 - 3567
• Main Authors: Imai, Jun, Maruya, Mikako, Yashiroda, Hideki, Yahara, Ichiro, Tanaka, Keiji
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 15-07-2003; Blackwell Publishing Ltd; Oxford University Press
• Subjects: 26S proteasome; Adenosine Triphosphate - metabolism; Antifungal Agents - pharmacology; assembly; ATP; Benzoquinones; Genes, Fungal; Hsp90; HSP90 Heat-Shock Proteins - antagonists & inhibitors; HSP90 Heat-Shock Proteins - drug effects; HSP90 Heat-Shock Proteins - genetics; HSP90 Heat-Shock Proteins - metabolism; Hydrolysis; Lactams, Macrocyclic; maintenance; Mutation; Peptide Hydrolases - genetics; Peptide Hydrolases - metabolism; Proteasome Endopeptidase Complex; Protein Processing, Post-Translational; Protein Subunits - metabolism; Quinones - pharmacology; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae - genetics; Temperature; yeast; Yeasts
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.1093/emboj/cdg349

Hsp90 has a diverse array of cellular roles including protein folding, stress response and signal transduction. Herein we report a novel function for Hsp90 in the ATP‐dependent assembly of the 26S proteasome. Functional loss of Hsp90 using a temperature‐sensitive mutant in yeast caused dissociation of the 26S proteasome. Conversely, these dissociated constituents reassembled in Hsp90‐dependent fashion both in vivo and in vitro; the process required ATP‐hydrolysis and was suppressed by the Hsp90 inhibitor geldanamycin. We also found genetic interactions between Hsp90 and several proteasomal Rpn (Regulatory particle non‐ATPase subunit) genes, emphasizing the importance of Hsp90 to the integrity of the 26S proteasome. Our results indicate that Hsp90 interacts with the 26S proteasome and plays a principal role in the assembly and maintenance of the 26S proteasome.