The molecular chaperone Hsp90 plays a role in the assembly and maintenance of the 26S proteasome.
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.
Imai
Jun
J
Department of Molecular Oncology and Department of Cell Biology, Tokyo Metropolitan Institute of Medical Science, Honkomagome 3-18-22, Bunkyo-ku, Tokyo 113-8613, CREST, Japan.
Maruya
Mikako
M
Yashiroda
Hideki
H
Yahara
Ichiro
I
Tanaka
Keiji
K
D000255:Adenosine Triphosphate / Q000378:metabolism; D000935:Antifungal Agents / Q000494:pharmacology; D016227:Benzoquinones; D005800:Genes, Fungal; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D006868:Hydrolysis; D047029:Lactams, Macrocyclic; D009154:Mutation; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D011499:Protein Processing, Post-Translational; D021122:Protein Subunits / Q000378:metabolism; D011809:Quinones / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D013696:Temperature
D000935:Antifungal Agents; D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D021122:Protein Subunits; D011809:Quinones; D000255:Adenosine Triphosphate; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; C001277:geldanamycin