Regulation of heat shock transcription factor 1 by stress-induced SUMO-1 modification

Heat shock transcription factor 1 (HSF1) mediates the induction of heat sho ck protein gene expression in cells exposed to elevated temperature and oth er stress conditions. In response to stress HSF1 acquires DNA binding abili ty and localizes to nuclear stress granules, but the molecular mechanisms t hat mediate these events are not understood. We report that HSF1 undergoes stress-induced modification at lysine 298 by the small ubiquitin-related pr otein called SUMO-1. Antibodies against SUMO-1 supershift the HSF1 DNA-bind ing complex, and modification of HSF1 in a reconstituted SUMO-1 reaction sy stem causes conversion of HSF1 to the DNA-binding form. HSF1 colocalizes wi th SUMO-1 in nuclear stress granules, which is prevented by mutation of lys ine 298. Mutation of lysine 298 also results in a significant decrease in s tress-induced transcriptional activity of HSF1 in vivo. This work implicate s SUMO-1 modification as an important modulator of HSF1 function in respons e to stress.