title: Requirement of Hsp105 in CoCl2-induced HIF-1α accumulation and transcriptional activation.
abstract: The mammalian stress protein Hsp105α protects cells from stress conditions. Several studies have indicated that Hsp105α is overexpressed in many types of solid tumors, which contain hypoxic microenvironments. However, the role of Hsp105α in hypoxic tumors remains largely unknown. We herein demonstrated the involvement of Hsp105α in HIF-1 functions induced by the hypoxia-mimetic agent CoCl2. While Hsp105α is mainly localized in the cytoplasm under normal conditions, a treatment with CoCl2induces the nuclear localization of Hsp105α, which correlated with HIF-1α expression levels. The overexpression of degradation-resistant HIF-1α enhances the nuclear localization of Hsp105α without the CoCl2treatment. The CoCl2-dependent transcriptional activation of HIF-1, which is measured using a reporter gene containing a HIF-responsive element, is reduced by the knockdown of Hsp105α. Furthermore, the CoCl2-induced accumulation of HIF-1α is enhanced by heat shock, which results in the nuclear localization of Hsp105, and is suppressed by the knockdown of Hsp105. Hsp105 associates with HIF-1α in CoCl2-treated cells. These results suggest that Hsp105α plays an important role in the functions of HIF-1 under hypoxic conditions, in which Hsp105α enhances the accumulation and transcriptional activity of HIF-1 through the HIF-1α-mediated nuclear localization of Hsp105α.
authors.affiliation: Department of Biochemistry and Molecular Biology, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Mikami
authors.affiliation: Department of Biochemistry and Molecular Biology, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan. Electronic address: ysaito@mb.kyoto-phu.ac.jp.
authors.forename: Youhei
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Department of Biochemistry and Molecular Biology, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
authors.forename: Namiko
authors.initials: N
authors.lastname: Okamoto
authors.affiliation: Department of Biochemistry and Molecular Biology, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
authors.forename: Ayana
authors.initials: A
authors.lastname: Kakihana
authors.affiliation: Department of Biochemistry and Molecular Biology, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Kuga
authors.affiliation: Department of Biochemistry and Molecular Biology, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan. Electronic address: nakayama@mb.kyoto-phu.ac.jp.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakayama
mesh_terms: D021581:Active Transport, Cell Nucleus; D015687:Cell Hypoxia; D002467:Cell Nucleus / Q000378:metabolism*; D003035:Cobalt / Q000633:toxicity*; D057809:HEK293 Cells; D050957:HSP110 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D018869:Heat-Shock Response; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D020218:Response Elements; D015533:Transcriptional Activation
chemical_list: C497442:HIF1A protein, human; D050957:HSP110 Heat-Shock Proteins; C097205:HSPH1 protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D003035:Cobalt; C018021:cobaltous chloride
keywords: CoCl(2); HIF-1α; Hsp105; Hypoxia; Tumor microenvironment