title: Insights into the regulation of heat shock transcription factor 1 SUMO-1 modification.
abstract: The transcriptional regulatory protein HSF1 is the key mediator of induced heat shock protein gene expression in response to elevated temperature and other stresses. Our previous studies identified stress-induced SUMO-1 modification of HSF1 as an important regulator of the DNA-binding activity of this factor. The underlying molecular mechanism by which stress leads to sumoylation of HSF1 was unknown. Prompted by previous studies indicating stress-induced phosphorylation at serine 307 of HSF1, a site very near the sumoylation site at lysine 298, we examined the role of this phosphorylation event in regulating SUMO-1 modification of HSF1. Using a combination of transfection and in vitro phosphorylation/sumoylation experiments, our results indicate that phosphorylation at serine 307 stimulates sumoylation of HSF1. Our results also reveal a role for a conserved leucine zipper sequence in the C-terminal region of HSF1 in inhibiting its SUMO-1 modification. Based on these data, we postulate that phosphorylation at serine 307 could stimulate HSF1 sumoylation by causing a conformation change that relieves the inhibitory effect of the C-terminal leucine zipper.
authors.affiliation: Department of Molecular and Cellular Biochemistry, Chandler Medical Center, University of Kentucky, Lexington, KY 40536-0298, USA.
authors.forename: Roland S
authors.initials: RS
authors.lastname: Hilgarth
authors.forename: Yiling
authors.initials: Y
authors.lastname: Hong
authors.forename: Ok-Kyong
authors.initials: OK
authors.lastname: Park-Sarge
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Sarge
mesh_terms: D000595:Amino Acid Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006367:HeLa Cells; D000076249:Heat Shock Transcription Factors; D006358:Hot Temperature; D006801:Humans; D007930:Leucine / Q000737:chemistry; D008239:Lysine / Q000737:chemistry; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D008957:Models, Genetic; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010766:Phosphorylation; D011233:Precipitin Tests; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D025842:SUMO-1 Protein / Q000737:chemistry / Q000378:metabolism*; D012694:Serine / Q000737:chemistry; D013696:Temperature; D014157:Transcription Factors; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D025842:SUMO-1 Protein; D014157:Transcription Factors; D012694:Serine; D000071679:Glycogen Synthase Kinase 3 beta; D019950:Mitogen-Activated Protein Kinase 1; D038362:Glycogen Synthase Kinase 3; D007930:Leucine; D008239:Lysine