Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Proc Natl Acad Sci U S A
1999 Feb 16;964:1439-44. doi: 10.1073/pnas.96.4.1439.
Show Gene links
Show Anatomy links
The molecular chaperone Hsp90 can negatively regulate the activity of a glucocorticosteroid-dependent promoter.
Kang KI
,
Meng X
,
Devin-Leclerc J
,
Bouhouche I
,
Chadli A
,
Cadepond F
,
Baulieu EE
,
Catelli MG
.
???displayArticle.abstract??? Hsp90, a molecular chaperone required for the functioning of glucocorticosteroid receptor (GR), ensures, by direct interaction, the conformational competence of the steroid-binding pocket. In addition to having this positive function, Hsp90 maintains steroid receptors in an inactive form in the absence of hormone. However, neither the participation of Hsp90 once the pathway has been activated by the ligand nor the importance of increased Hsp90 levels in determining the amplitude of the response has ever been assessed directly. Here, by increasing the Hsp90/GR ratio in the nuclear compartment, we found an attenuation of the response to glucocorticosteroids that was not due to a nonspecific or toxic effect of the Hsp90 modified by nuclear targeting. Since this negative effect was more pronounced at high levels of hormone, when receptor and Hsp90 are maximally dissociated, the possibility of an interaction between Hsp90 and GR, already activated to a DNA-binding form, was directly investigated. Indeed GR, after in vivo activation by ligand, was still able to reassociate with Hsp90, suggesting that this interaction plays a role in vivo, possibly in receptor recycling. Moreover, the GR binding to its DNA response element was inhibited by an excess of Hsp90, pointing to a function of Hsp90 in the nuclear compartment. It is thus proposed that an increased Hsp90/GR ratio influences the responsiveness to ligand at a step that is after receptor activation. This increased ratio may be of pathophysiological relevance in the different circumstances that lead to an elevated level of nuclear Hsp90.
Ali,
HSP90 interacts with and regulates the activity of heat shock factor 1 in Xenopus oocytes.
1998, Pubmed,
Xenbase
Ali,
HSP90 interacts with and regulates the activity of heat shock factor 1 in Xenopus oocytes.
1998,
Pubmed
,
Xenbase
Beato,
Steroid hormone receptors: many actors in search of a plot.
1995,
Pubmed
Bohen,
Hold 'em and fold 'em: chaperones and signal transduction.
1995,
Pubmed
Bohen,
Isolation of Hsp90 mutants by screening for decreased steroid receptor function.
1993,
Pubmed
Bresnick,
Evidence that the 90-kDa heat shock protein is necessary for the steroid binding conformation of the L cell glucocorticoid receptor.
1989,
Pubmed
Cadepond,
Heat shock protein 90 as a critical factor in maintaining glucocorticosteroid receptor in a nonfunctional state.
1991,
Pubmed
Catelli,
The common 90-kd protein component of non-transformed '8S' steroid receptors is a heat-shock protein.
1985,
Pubmed
Collier,
The dynamic state of heat shock proteins in chicken embryo fibroblasts.
1986,
Pubmed
DeFranco,
Molecular chaperones and subcellular trafficking of steroid receptors.
1998,
Pubmed
Devin-Leclerc,
Interaction and dissociation by ligands of estrogen receptor and Hsp90: the antiestrogen RU 58668 induces a protein synthesis-dependent clustering of the receptor in the cytoplasm.
1998,
Pubmed
Gasc,
Nuclear localization of two steroid receptor-associated proteins, hsp90 and p59.
1990,
Pubmed
Gouilleux,
Cooperation between structural elements in hormono-regulated transcription from the mouse mammary tumor virus promoter.
1991,
Pubmed
Inano,
Heat shock protein 90 strongly stimulates the binding of purified estrogen receptor to its responsive element.
1994,
Pubmed
,
Xenbase
Joab,
Common non-hormone binding component in non-transformed chick oviduct receptors of four steroid hormones.
,
Pubmed
Kang,
In vivo functional protein-protein interaction: nuclear targeted hsp90 shifts cytoplasmic steroid receptor mutants into the nucleus.
1994,
Pubmed
Mangelsdorf,
The nuclear receptor superfamily: the second decade.
1995,
Pubmed
Meng,
Mutational analysis of Hsp90 alpha dimerization and subcellular localization: dimer disruption does not impede "in vivo' interaction with estrogen receptor.
1996,
Pubmed
Nathan,
Mutational analysis of Hsp90 function: interactions with a steroid receptor and a protein kinase.
1995,
Pubmed
Panaretou,
ATP binding and hydrolysis are essential to the function of the Hsp90 molecular chaperone in vivo.
1998,
Pubmed
Picard,
A movable and regulable inactivation function within the steroid binding domain of the glucocorticoid receptor.
1988,
Pubmed
Picard,
Reduced levels of hsp90 compromise steroid receptor action in vivo.
1990,
Pubmed
Pratt,
Steroid receptor interactions with heat shock protein and immunophilin chaperones.
1997,
Pubmed
Pratt,
A region in the steroid binding domain determines formation of the non-DNA-binding, 9 S glucocorticoid receptor complex.
1988,
Pubmed
Prodromou,
Identification and structural characterization of the ATP/ADP-binding site in the Hsp90 molecular chaperone.
1997,
Pubmed
Radanyi,
Chick heat-shock protein of Mr = 90,000, free or released from progesterone receptor, is in a dimeric form.
1989,
Pubmed
Renoir,
The nonactivated progesterone receptor is a nuclear heterooligomer.
1990,
Pubmed
Sabbah,
The 90 kDa heat-shock protein (hsp90) modulates the binding of the oestrogen receptor to its cognate DNA.
1996,
Pubmed
Scherrer,
Evidence that the hormone binding domain of steroid receptors confers hormonal control on chimeric proteins by determining their hormone-regulated binding to heat-shock protein 90.
1993,
Pubmed
Segard-Maurel,
Glucocorticosteroid receptor dimerization investigated by analysis of receptor binding to glucocorticosteroid responsive elements using a monomer-dimer equilibrium model.
1996,
Pubmed
Segnitz,
The function of steroid hormone receptors is inhibited by the hsp90-specific compound geldanamycin.
1997,
Pubmed
Shaknovich,
Conformational activation of a basic helix-loop-helix protein (MyoD1) by the C-terminal region of murine HSP90 (HSP84).
1992,
Pubmed
Sikorski,
In vitro mutagenesis and plasmid shuffling: from cloned gene to mutant yeast.
1991,
Pubmed
Stebbins,
Crystal structure of an Hsp90-geldanamycin complex: targeting of a protein chaperone by an antitumor agent.
1997,
Pubmed
Tsai,
Molecular mechanisms of action of steroid/thyroid receptor superfamily members.
1994,
Pubmed
Whitesell,
Stable and specific binding of heat shock protein 90 by geldanamycin disrupts glucocorticoid receptor function in intact cells.
1996,
Pubmed