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 ( R egulatory p article n on‐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.