Abstract
The role of stress-induced increases in SUMO2/3 conjugation during the heat shock response (HSR) has remained enigmatic. We investigated SUMO signal transduction at the proteomic and functional level during the HSR in cells depleted of proteostasis network components via chronic heat shock factor 1 inhibition. In the recovery phase post heat shock, high SUMO2/3 conjugation was prolonged in cells lacking sufficient chaperones. Similar results were obtained upon inhibiting HSP90, indicating that increased chaperone activity during the HSR is critical for recovery to normal SUMO2/3 levels post-heat shock. Proteasome inhibition likewise prolonged SUMO2/3 conjugation, indicating that stress-induced SUMO2/3 targets are subsequently degraded by the ubiquitin-proteasome system. Functionally, we suggest that SUMOylation can enhance the solubility of target proteins upon heat shock, a phenomenon that we experimentally observed in vitro. Collectively, our results implicate SUMO2/3 as a rapid response factor that coordinates proteome degradation and assists the maintenance of proteostasis upon proteotoxic stress.