Hsp90 inhibition promotes proteasome function in vascular endothelial cells

Dysfunction of proteasome has been implicated in the development of many human diseases. Promoting proteasome function may have profound clinical interests. We have shown in our previous study that proteasome is inhibited by O-GlcNAc modification, which has been shown in another study to be decreased by Hsp90 inhibition as a result of the degradation of O-GlcNAc transferase (OGT). In this study we examined the effect of Hsp90 inhibition on proteasome function in vascular endothelial cells. We found that inhibition of Hsp90 promoted proteasome function, as indicated by proteasome chymotrypsin-like peptidase activity and the clearance of ubiquitinated proteins. Thus, Hsp90 inhibitors may be used to promote proteasome function pharmacologically.