Abstract
AbstractUnliganded glucocorticoid receptors (GRs) released from chromatin after hormone withdrawal remain associated with the nucleus within a novel subnuclear compartment that serves as a nuclear export staging area. We set out to examine whether unliganded nuclear receptors cycle between distinct subnuclear compartments or require cytoplasmic transit to regain hormone and chromatin-binding capacity. Hormone-withdrawn rat GrH2 hepatoma cells were permeabilized with digitonin to deplete cytoplasmic factors, and then hormone-binding and chromatin-binding properties of the recycled nuclear GRs were measured. We found that recycled nuclear GRs do not require cytosolic factors or ATP to rebind hormone. Nuclear GRs that rebind hormone in permeabilized cells target to high-affinity chromatin-binding sites at 30 C, but not 0 C, in the presence of ATP. Since geldanamycin, a heat shock protein-90 (hsp90)-binding drug, inhibits hormone binding to recycled nuclear GRs, hsp90 may be required to reassemble the receptor into a form capable of productive interactions with hormone. Geldanamycin also inhibits GR release from chromatin during hormone withdrawal, suggesting that hsp90 chaperone function may play multiple roles to facilitate chromatin recycling of GR.
References
66
Referenced
46
10.1146/annurev.ge.19.120185.001233
/ Annu Rev Genet / Steroid receptor regulated transcription of genes and gene networks. by Yamamoto (1985)10.1126/science.3283939
/ Science / The steroid and thyroid hormone receptor superfamily. by Evans (1988)10.1016/0092-8674(95)90199-X
/ Cell / The nuclear receptor superfamily: the second decade. by Mangelsdorf (1995)10.1146/annurev.bi.63.070194.002315
/ Annu Rev Biochem / Molecular mechanisms of action of steroid/thyroid receptor superfamily members. by Tsai (1994)10.1016/0092-8674(91)90021-P
/ Cell / The orientation and spacing of core DNA-binding motifs dictate selective transcriptional responses to three nuclear receptors. by Näär (1991)10.1016/0092-8674(91)90020-Y
/ Cell / Direct repeats as selective response elements for the thyroid hormone retinoic acid and vitamin D3 receptors. by Umesono (1991)10.1126/science.2176746
/ Science / Regulation of progesterone receptor-mediated transcription by phosphorylation. by Denner (1990)10.1126/science.1749936
/ Science / Dopaminergic and ligand-independent activation of steroid hormone receptors. by Power (1991){'key': '2020071614252961000_R9', 'first-page': '26', 'article-title': 'Effects of okadaic acid, a protein phosphatase inhibitor, on glucocorticoid receptor mediated enhancement.', 'volume': '6', 'author': 'Somers', 'year': '1992', 'journal-title': 'Mol Endocrinol'}
/ Mol Endocrinol / Effects of okadaic acid, a protein phosphatase inhibitor, on glucocorticoid receptor mediated enhancement. by Somers (1992){'key': '2020071614252961000_R10', 'first-page': '577', 'article-title': 'Multiple signaling pathways activate the chicken progesterone receptor.', 'volume': '8', 'author': 'Zhang', 'year': '1994', 'journal-title': 'Mol Endocrinol'}
/ Mol Endocrinol / Multiple signaling pathways activate the chicken progesterone receptor. by Zhang (1994){'key': '2020071614252961000_R11', 'first-page': '4', 'article-title': 'Steroid receptors and their associated proteins.', 'volume': '7', 'author': 'Smith', 'year': '1993', 'journal-title': 'Mol Endocrinol'}
/ Mol Endocrinol / Steroid receptors and their associated proteins. by Smith (1993)10.1016/S0021-9258(20)80556-0
/ J Biol Chem / The role of heat shock proteins in regulating the function, folding, and trafficking of the glucocorticoid receptor. by Pratt (1993){'key': '2020071614252961000_R13', 'first-page': '306', 'article-title': 'Steroid receptor interactions with heat shock protein and immunophilin chaperones.', 'volume': '18', 'author': 'Pratt', 'year': '1997', 'journal-title': 'Endocr Rev'}
/ Endocr Rev / Steroid receptor interactions with heat shock protein and immunophilin chaperones. by Pratt (1997)10.1038/377454a0
/ Nature / A transcriptional co-repressor that interacts with nuclear hormone receptors. by Chen (1995)10.1038/377397a0
/ Nature / Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor. by Horlein (1995){'key': '2020071614252961000_R16', 'first-page': '1418', 'article-title': 'Dynamics of heat shock protein 90-progesterone receptor binding and the disactivation loop model for steroid receptor complexes.', 'volume': '7', 'author': 'Smith', 'year': '1993', 'journal-title': 'Mol Endocrinol'}
/ Mol Endocrinol / Dynamics of heat shock protein 90-progesterone receptor binding and the disactivation loop model for steroid receptor complexes. by Smith (1993){'key': '2020071614252961000_R17', 'first-page': '670', 'article-title': 'Binding of p23 and hsp90 during assembly with the progesterone receptor.', 'volume': '9', 'author': 'Johnson', 'year': '1995', 'journal-title': 'Mol Endocrinol'}
/ Mol Endocrinol / Binding of p23 and hsp90 during assembly with the progesterone receptor. by Johnson (1995)10.1074/jbc.271.22.12833
/ J Biol Chem / Reconstitution of the steroid receptor-hsp90 heterocomplex assembly system of rabbit reticulocyte lysate. by Dittmar (1996)10.1128/MCB.15.12.6804
/ Mol Cell Biol / Progesterone receptor structure and function altered by geldanamycin, an hsp90-binding agent. by Smith (1995){'key': '2020071614252961000_R20', 'first-page': '420', 'article-title': 'Molecular cloning of human p48, a transient component of progesterone receptor complexes and an hsp70-binding protein.', 'volume': '10', 'author': 'Prapapanich', 'year': '1996', 'journal-title': 'Mol Endocrinol'}
/ Mol Endocrinol / Molecular cloning of human p48, a transient component of progesterone receptor complexes and an hsp70-binding protein. by Prapapanich (1996)10.1016/S0021-9258(18)83689-4
/ J Biol Chem / Evidence that the 90-kDa heat shock protein is necessary for the steroid binding conformation of the L cell glucocorticoid receptor. by Bresnick (1989){'key': '2020071614252961000_R22', 'first-page': '315', 'article-title': 'Nucleocytoplasmic shuttling of steroid receptors. In: Litwack G (ed) Vitamins and Hormones.', 'volume': '51', 'author': 'DeFranco', 'year': '1995', 'journal-title': 'Academic Press, New York, vol'}
/ Academic Press, New York, vol / Nucleocytoplasmic shuttling of steroid receptors. In: Litwack G (ed) Vitamins and Hormones. by DeFranco (1995)10.1002/j.1460-2075.1991.tb04954.x
/ EMBO J / Nucleocytoplasmic shuttling of the progesterone receptor. by Guiochon-Mantel (1991){'key': '2020071614252961000_R24', 'first-page': '837', 'article-title': 'Internuclear migration of chicken progesterone receptor, but not simian virus-40 large tumor antigen, in transient heterokaryons.', 'volume': '6', 'author': 'Chandran', 'year': '1992', 'journal-title': 'Mol Endocrinol'}
/ Mol Endocrinol / Internuclear migration of chicken progesterone receptor, but not simian virus-40 large tumor antigen, in transient heterokaryons. by Chandran (1992)10.1073/pnas.90.8.3588
/ Proc Natl Acad Sci USA / Bidirectional transport of glucocorticoid receptors across the nuclear envelope. by Madan (1993)10.1242/jcs.106.4.1377
/ J Cell Sci / The antiestrogen ICI 182780 disrupts estrogen receptor nucleocytoplasmic shuttling. by Dauvois (1993){'key': '2020071614252961000_R27', 'first-page': '3', 'article-title': 'Assessment of glucocorticoid receptor-heat shock protein 90 interactions in vivo during nucleocytoplasmic trafficking.', 'volume': '10', 'author': 'Yang', 'year': '1996', 'journal-title': 'Mol Endocrinol'}
/ Mol Endocrinol / Assessment of glucocorticoid receptor-heat shock protein 90 interactions in vivo during nucleocytoplasmic trafficking. by Yang (1996)10.1016/0092-8674(89)90052-4
/ Cell / Mechanisms of nuclear localization of the progesterone receptor: evidence for interactions between monomers. by Guiochon-Mantel (1989)10.1002/j.1460-2075.1992.tb05453.x
/ EMBO J / Cooperation of proto-signals for nuclear accumulation of estrogen and progesterone receptors. by Ylikomi (1992)10.1210/endo-120-4-1232
/ Endocrinology / Intracellular localization of the glucocorticoid receptor: evidence for cytoplasmic and nuclear localization. by Wikström (1987)10.1091/mbc.1.3.291
/ Cell Regul / Signal transduction by steroid hormones: nuclear localization is differentially regulated in estrogen and progesterone receptors. by Picard (1990)10.1210/mend-3-8-1279
/ Mol Endocrinol / v-mos Oncoproteins affect the nuclear retention and reutilization of glucocorticoid receptors. by Qi (1989)10.1073/pnas.93.10.4845
/ Proc Natl Acad Sci USA / Visualization of glucocorticoid receptor translocation and intranuclear organization in living cells with a green fluorescent protein chimera. by Htun (1996)10.1083/jcb.137.3.523
/ J Cell Biol / Subnuclear trafficking of glucocorticoid receptors in vitro: chromatin recycling and nuclear export. by Yang (1997){'key': '2020071614252961000_R35', 'first-page': '1191', 'article-title': 'Determinants of subcellular distribution of the glucocorticoid receptor.', 'volume': '10', 'author': 'Sackey', 'year': '1996', 'journal-title': 'Mol Endocrinol'}
/ Mol Endocrinol / Determinants of subcellular distribution of the glucocorticoid receptor. by Sackey (1996)10.1016/0092-8674(81)90409-8
/ Cell / Mammary tumor virus DNA contains sequences required for its hormone-regulated transcription. by Ucker (1981)10.1038/324686a0
/ Nature / In vivo protein-DNA interactions in a glucocorticoid response element require the presence of hormone. by Becker (1986)10.1016/0092-8674(84)90523-3
/ Cell / Hormonally induced alterations of chromatin structure in the polyadenylation and transcription termination regions of the chicken ovalbumin gene. by Zaret (1984)10.1002/j.1460-2075.1991.tb07797.x
/ EMBO J / Glucocorticoids are required for establishment and maintenance of an alteration in chromatin structure:induction leads to a reversible disruption of nucleosomes over an enhancer. by Reik (1991)10.1016/0022-4731(76)90042-X
/ J Steroid Biochem / Kinetics of glucocorticoid-receptor complexes in rat thymus cells. by Munck (1976)10.1083/jcb.111.3.807
/ J Cell Biol / Nuclear protein import in permeabilized mammalian cells requires soluble cytoplasmic factors. by Adam (1990)10.1128/MCB.14.8.5088
/ Mol Cell Biol / Differential roles of heat shock protein 70 in the in vitro nuclear import of glucocorticoid receptor and simian virus 40 large tumor antigen. by Yang (1994)10.1128/MCB.16.5.1989
/ Mol Cell Biol / ATP-dependent release of glucocorticoid receptors from the nuclear matrix. by Tang (1996)10.1074/jbc.272.12.8007
/ J Biol Chem / Nucleotides and Two Functional States of hsp90. by Sullivan (1997){'key': '2020071614252961000_R45', 'first-page': '23843', 'article-title': 'The amino-terminal domain of heat shock protein 90 (hsp90) that binds geldanamycin is an ATP/ADP switch domain that regulates hsp90 conformation J Biol Chem', 'volume': '272', 'author': 'Grenert', 'year': '1997'}
/ The amino-terminal domain of heat shock protein 90 (hsp90) that binds geldanamycin is an ATP/ADP switch domain that regulates hsp90 conformation J Biol Chem by Grenert (1997)10.1074/jbc.272.34.21213
/ J Biol Chem / Folding of the glucocorticoid receptor by the heat shock protein (hsp) 90-based chaperone machinery. by Dittmar (1997){'key': '2020071614252961000_R47', 'first-page': '705', 'article-title': 'Stable and specific binding of heat shock protein 90 by geldanamycin disrupts glucocorticoid receptor function in intact cells.', 'volume': '10', 'author': 'Whitesell', 'year': '1996', 'journal-title': 'Mol Endocrinol'}
/ Mol Endocrinol / Stable and specific binding of heat shock protein 90 by geldanamycin disrupts glucocorticoid receptor function in intact cells. by Whitesell (1996)10.1016/0022-4731(89)90069-1
/ J Steroid Biochem / A dynamic model of glucocorticoid receptor phosphorylation and recycling in intact cells. by Orti (1989)10.1016/0092-8674(90)90087-U
/ Cell / Nucleosome positioning modulates accessibility of regulatory proteins to the mouse mammary tumor virus promoter. by Pina (1990)10.1128/MCB.11.2.688
/ Mol Cell Biol / Transcription factor access is mediated by accurately positioned nucleosomes on the mouse mammary tumor virus promoter. by Archer (1991)10.1083/jcb.123.6.1649
/ J Cell Biol / Inhibition of nuclear protein import by nonhydrolyzable analogues of GTP and identification of the small GTPase Ran/TC4 as an essential nuclear factor. by Melchior (1993)10.1038/365661a0
/ Nature / The GTP-binding protein Ran/TC4 is required for protein import into the nucleus. by Moore (1993)10.1615/CritRevEukarGeneExpr.v7.i1-2.40
/ Crit Rev Eukaryot Gene Expr / Molecular mechanisms of nuclear protein transport. by Moroianu (1997)10.1091/mbc.8.5.795
/ Mol Biol Cell / A role for HDJ-2/HSDJ in correcting subnuclear trafficking, transactivation and transrepression defects of a glucocorticoid receptor zinc finger mutant. by Tang (1997)10.1038/502
/ Nat Genet / Chaperone suppression of aggregation and altered subcellular proteasome localization imply protein misfolding in SCA1. by Cummings (1998)10.1016/S0163-7258(98)00013-8
/ Pharmacol Ther / The 90 kDa molecular chaperone family: structure, function, and clinical applications. A comprehensive review. by Csermely (1998)10.1128/MCB.12.11.5059
/ Mol Cell Biol / Conformational activation of a basic helix-loop-helix protein (MyoD1) by the C-terminal region of murine HSP90 (HSP84). by Shaknovich (1992)10.1016/S0021-9258(17)42001-1
/ J Biol Chem / Structural and functional aspects of basic helix-loop-helix protein folding by heat shock protein 90. by Shue (1994)10.1016/S0021-9258(18)45746-8
/ J Biol Chem / Structural and functional reconstitution of the glucocorticoid receptor-hsp90 complex. by Scherrer (1990)10.1042/bj3140205
/ Biochem J / The 90-KDa heat-shock protein (hsp90) modulates the binding of the oestrogen receptor to its cognate DNA. by Sabbah (1996)10.1016/S0092-8674(00)80203-2
/ Cell / Crystal structure of an hsp90-geldanamycin complex: targeting of a protein chaperone by an antitumor agent. by Stebbins (1997){'key': '2020071614252961000_R62', 'first-page': '1266', 'article-title': 'Transcriptional activation by the estrogen receptor requires a conformational change in the ligand binding domain.', 'volume': '7', 'author': 'Beekman', 'year': '1993', 'journal-title': 'Mol Endocrinol'}
/ Mol Endocrinol / Transcriptional activation by the estrogen receptor requires a conformational change in the ligand binding domain. by Beekman (1993)10.1038/39645
/ Nature / Molecular basis of agonism and antagonism in the oestrogen receptor. by Brzozowski (1997)10.1073/pnas.95.11.5998
/ Proc Natl Acad Sci USA / Crystallographic comparison of the estrogen and progesterone receptor’s ligand binding domain. by Tanenbaum (1998)10.1016/S0021-9258(19)38489-3
/ J Biol Chem / Mapping the HSP90 binding region of the glucocorticoid receptor. by Howard (1990)10.1210/endo-114-1-274
/ Endocrinology / Characterization of a monoclonal antibody to the rat liver glucocorticoid receptor. by Gametchu (1984)
Dates
Type | When |
---|---|
Created | 11 years, 7 months ago (Jan. 8, 2014, 12:30 p.m.) |
Deposited | 3 years, 5 months ago (March 21, 2022, 8:26 p.m.) |
Indexed | 5 months, 1 week ago (March 19, 2025, 10:27 a.m.) |
Issued | 26 years, 5 months ago (March 1, 1999) |
Published | 26 years, 5 months ago (March 1, 1999) |
Published Print | 26 years, 5 months ago (March 1, 1999) |
@article{Liu_1999, title={Chromatin Recycling of Glucocorticoid Receptors: Implications for Multiple Roles of Heat Shock Protein 90}, volume={13}, ISSN={1944-9917}, url={http://dx.doi.org/10.1210/mend.13.3.0258}, DOI={10.1210/mend.13.3.0258}, number={3}, journal={Molecular Endocrinology}, publisher={The Endocrine Society}, author={Liu, Jimin and DeFranco, Donald B.}, year={1999}, month=mar, pages={355–365} }