title: The induction mechanism of the molecular chaperone HSP70 in the gastric mucosa by Geranylgeranylacetone (HSP-inducer).
abstract: To elucidate the induction mechanism of HSP70 by geranylgeranylacetone (GGA), we investigated GGA specific binding proteins using a GGA-affinity column. Alteration of chaperone activity of HSP70 and binding affinity of HSP70 to heat shock factor-1 (HSF-1) was evaluated in the presence or absence of GGA. The binding domain of HSP70 to GGA was also analyzed. A 70-kDa protein eluted by 10 mM GGA from the GGA-affinity column was identical to constitutively expressed HSP70 on immunoblotting. GGA-binding domain of HSP70 was C-terminal of the protein as peptide-binding domain (HSP70C). The chaperone activity of HSP70 and recombinant HSP70C was suppressed by GGA. Furthermore, dissociation of the HSP70 from HSF-1 was observed in the presence of GGA. GGA preferentially binds to the C-terminal of HSP70 which binds to HSF-1. After dissociation of HSP70, free HSF-1 could acquire the ability to bind to HSE (the promoter region of HSP70) gene.
authors.affiliation: Department of Internal Medicine and Gastroenterology, Akita University School of Medicine, 1-1-1 Hondo, Akita City 010-8543, Japan. otaka@med.akita-u.ac.jp
authors.forename: Michiro
authors.initials: M
authors.lastname: Otaka
authors.forename: Soh
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Kaori
authors.initials: K
authors.lastname: Ogasawara
authors.forename: Yuka
authors.initials: Y
authors.lastname: Takaoka
authors.forename: Susumu
authors.initials: S
authors.lastname: Noguchi
authors.forename: Toshio
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Akira
authors.initials: A
authors.lastname: Nakai
authors.forename: Masaru
authors.initials: M
authors.lastname: Odashima
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Matsuhashi
authors.forename: Sumio
authors.initials: S
authors.lastname: Watanabe
authors.forename: Hideaki
authors.initials: H
authors.lastname: Itoh
mesh_terms: D000818:Animals; D001665:Binding Sites; D004224:Diterpenes / Q000737:chemistry*; D004789:Enzyme Activation; D005753:Gastric Mucosa / Q000737:chemistry* / Q000201:enzymology*; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry* / Q000378:metabolism*; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats
chemical_list: D004224:Diterpenes; D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; C031049:geranylgeranylacetone