Regulation of nuclear retention of glucocorticoid receptor by nuclear Hsp90.
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.
Tago
Katsuya
K
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.
Tsukahara
Fujiko
F
Naruse
Mitsuhide
M
Yoshioka
Toshimasa
T
Takano
Kazue
K
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
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