title: Evolutionarily conserved domain of heat shock transcription factor negatively regulates oligomerization and DNA binding.
abstract: Heat shock transcription factor (HSF) regulates the expression of genes encoding molecular chaperones and stress-responsive proteins. Conversion of HSF from a monomer to a homotrimer or heterotrimer is essential for its binding to heat shock elements (HSEs) comprised of inverted repeats of the pentamer nGAAn. Here, we constructed various human HSF1 derivatives and analyzed their transcriptional activity through the continuously and discontinuously arranged nGAAn units. We identified a short stretch of amino acids that inhibits the activation ability of HSF1, especially through discontinuous HSEs. This stretch is conserved in HSFs of various organisms, interacts with the hydrophobic repeat regions that mediate HSF oligomerization, and impedes homotrimer formation and DNA binding. This conserved domain plays an important role in maintaining HSF in an inactive monomeric form.
authors.affiliation: Division of Health Sciences, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.
authors.forename: Azumi
authors.initials: A
authors.lastname: Ota
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Enoki
authors.forename: Noritaka
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Maki
authors.initials: M
authors.lastname: Sawai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakurai
mesh_terms: D005075:Biological Evolution; D001704:Biopolymers / Q000737:chemistry*; D017124:Conserved Sequence; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D000076249:Heat Shock Transcription Factors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*
chemical_list: D001704:Biopolymers; D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D014157:Transcription Factors; D004247:DNA
keywords: CD; DBD; DNA-binding domain; EGS; GST; HA; HR; HSE; HSF; Heat shock transcription factor (HSF); Intramolecular interaction; Oligomer formation; Protein–DNA interaction; RD; conserved domain; ethylene glycol bis-(succinimidylsuccinate); glutathione S-transferase; heat shock element; heat shock transcription factor; hydrophobic heptad repeat; influenza hemagglutinin; regulatory domain