Regulation of HSF1 by stress-induced SUMO-1 modification

Heat shock transcription factor 1 (HSF1) mediates the induction of heat shock protein (hsp) gene expression in cells exposed to elevated temperature and other stress conditions. In response to stress HSF1 acquires DNA-binding ability and localizes to nuclear stress granules, but the molecular mechanisms which mediate these events are not understood. We report that HSF1 undergoes stress-induced modification at lysine 298 by the ubiquitin-related protein called SUMO-1. Antibodies against SUMO-1 supershift the HSF1 DNA-binding complex, and modification of HSF1 in a reconstituted SUMO-1 reaction system causes conversion of HSF1 to the DNA-binding form. HSF1 colocalizes with SUMO-1 in nuclear stress granules, which is prevented by mutation of lysine 298. Mutation of lysine 298 also results in a significant decrease in stress-induced transcriptional activity of HSF1 in vivo. This work implicates SUMO-1 modification as a important modulator of HSF1 function in response to stress. by gest on Sptem er 1, 2017 hp://w w w .jb.org/ D ow nladed from