title: Regulation of heat shock transcription factor 1 by stress-induced SUMO-1 modification.
abstract: Heat shock transcription factor 1 (HSF1) mediates the induction of heat shock protein 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 that mediate these events are not understood. We report that HSF1 undergoes stress-induced modification at lysine 298 by the small 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 an important modulator of HSF1 function in response to stress.
authors.affiliation: Department of Biochemistry, Chandler Medical Center, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Hong
authors.forename: R
authors.initials: R
authors.lastname: Rogers
authors.forename: M J
authors.initials: MJ
authors.lastname: Matunis
authors.forename: C N
authors.initials: CN
authors.lastname: Mayhew
authors.forename: M L
authors.initials: ML
authors.lastname: Goodson
authors.forename: O K
authors.initials: OK
authors.lastname: Park-Sarge
authors.forename: K D
authors.initials: KD
authors.lastname: Sarge
authors.forename: M
authors.initials: M
authors.lastname: Goodson
mesh_terms: D002451:Cell Compartmentation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D006367:HeLa Cells; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000302:isolation & purification / Q000378:metabolism*; D018869:Heat-Shock Response; D006358:Hot Temperature; D006801:Humans; D008025:Ligases / Q000302:isolation & purification / Q000378:metabolism*; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D014157:Transcription Factors / Q000302:isolation & purification / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases
chemical_list: D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases; D008025:Ligases; D008239:Lysine