title: Regulation of nuclear retention of glucocorticoid receptor by nuclear Hsp90.
abstract: Heat shock protein 90 (Hsp90) has been demonstrated in both cytoplasm and nucleus, and regulates cytoplasmic retention of glucocorticoid receptor (GR). However, the role of nuclear Hsp90 in GR trafficking is less characterized. The present study examined the role of Hsp90 in nuclear retention of GR after ligand withdrawal. Hsp90 inhibitors; geldanamycin (GA) and radicicol (Rad), significantly accelerated nuclear export of GR after withdrawal of ligands including dexamethasone, corticosterone and RU486. GA accelerated relocalization of GR in the cytoplasm even when reimport of GR into the nucleus was inhibited by okadaic acid or when novel GR synthesis was inhibited by cycloheximide. Overexpression of wild type or nuclear-targeted Hsp90 attenuated Hsp90 inhibitor-induced acceleration of GR nuclear export, although nuclear Hsp90 showed higher activity than the wild type. Only nuclear-targeted Hsp90 prolonged basal nuclear retention of GR after withdrawal of dexamethasone and corticosterone. These results suggest that nuclear Hsp90 regulates the nuclear retention of GR.
authors.affiliation: Department of Medicine, Institution of Clinical Endocrinology, School of Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Tago
authors.forename: Fujiko
authors.initials: F
authors.lastname: Tsukahara
authors.forename: Mitsuhide
authors.initials: M
authors.lastname: Naruse
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Yoshioka
authors.forename: Kazue
authors.initials: K
authors.lastname: Takano
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D016227:Benzoquinones; D019556:COS Cells; D003345:Corticosterone / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D047029:Lactams, Macrocyclic; D007783:Lactones / Q000494:pharmacology; D008024:Ligands; D018942:Macrolides; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology; D021381:Protein Transport / Q000187:drug effects; D011809:Quinones / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D014162:Transfection
chemical_list: D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D007783:Lactones; D008024:Ligands; D018942:Macrolides; D009687:Nuclear Proteins; D011809:Quinones; D011965:Receptors, Glucocorticoid; C411470:glucocorticoid receptor alpha; D003907:Dexamethasone; C035359:monorden; D003345:Corticosterone; C001277:geldanamycin