scholarly journals Cyclophilin-40: evidence for a dimeric complex with hsp90

1995 ◽  
Vol 307 (1) ◽  
pp. 5-8 ◽  
Author(s):  
K Hoffmann ◽  
R E Handschumacher
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Fusion Protein ◽  
Steroid Receptors ◽  
Heat Shock Protein 90 ◽  
Binding Activity ◽  
Dimeric Complex ◽  
Glutathione S Transferase ◽  
High Concentration ◽  
Cyclophilin 40

The expression of human cyclophilin 40 (CyP-40) as a glutathione S-transferase fusion protein has provided a means to identify cellular components that are in association with this ubiquitous protein. When the fusion protein was coupled to a GSH affinity matrix, heat-shock protein 90 (hsp90) was found to be the predominant associated protein in all tissue extracts examined. The relatively high concentration of each of these proteins in various tissues indicates that the dimeric complex exists in concentrations that exceed those of the inactive steroid receptors of which each protein is a component. Association does not occur with heat-shock protein 70 and is not affected by cyclosporin A (CsA). Independent expression of two domains of CyP-40 permitted dissociation of N-terminal isomerase and CsA binding activity from the hsp90 binding site, which is located at the FKBP-59-like C-terminal region. The biological association of CyP-40 with hsp90 in many tissues may reflect a conjoint role in protein folding and trafficking.

Disruption of the Glucocorticoid Receptor Assembly with Heat Shock Protein 90 by a Peptidic Antiglucocorticoid

1997 ◽  
Vol 11 (7) ◽  
pp. 962-972 ◽  
Author(s):  
Hai-Pascal Dao-Phan ◽  
Pierre Formstecher ◽  
Philippe Lefebvre
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Cultured Cells ◽  
Protein A ◽  
Heat Shock Protein 90 ◽  
Specific Protein ◽  
Binding Activity ◽  
Independent Manner

Abstract Association of glucocorticoid (GR) and progesterone (PR) receptors with a set of molecular chaperones, including the 90-kDa heat shock protein (hsp90), is a dynamic process required for proper folding and maintaining these nuclear receptors under a transcriptionally inactive, ligand-responsive state. Mutational studies of the chicken hsp90 complementary DNA suggested that three regions of this protein (A, B, and Z) interact with the hormone-binding domain of GR, whereas region A is dispensable for hsp90 binding to PR. We found that this 69-amino acid region can be narrowed down to a 35-mer α-helical, acidic peptide, which is by itself able to inhibit hsp90 association to GR translated in vitro. The hsp90-free GR did not bind ligand, but was devoid of any specific DNA-binding activity, and higher peptide concentrations specifically inhibited the binding of activated GR to DNA. When overexpressed in cultured cells, this peptide acted as an antiglucocorticoid and inhibited the antiactivating protein-1 activity and the ligand-dependent nuclear transfer of GR. None of these effects, either in vivo and in vitro, was observed for PR. The region from residue 232 to residue 265 of hsp90 is, therefore, a domain critical for its association to GR, an association that is a prerequisite for receptor transcriptional activity. More importantly, these results demonstrate that targeting specific protein/protein interaction interfaces is a powerful means to specifically modulate nuclear receptor signaling pathways in a ligand-independent manner.

scholarly journals Polymorphic glutathione S-transferase subunit 3 of rat liver exhibits different susceptibilities to carbon tetrachloride: differences in their interactions with heat-shock protein 90

2003 ◽  
Vol 372 (2) ◽  
pp. 611-616 ◽  
Author(s):  
Jun MAYAMA ◽  
Takayuki KUMANO ◽  
Makoto HAYAKARI ◽  
Takehiko YAMAZAKI ◽  
Shu AIZAWA ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 90 ◽  
Hsp90 Inhibitor ◽  
Glutathione S Transferase ◽  
Ccl4 Administration ◽  
A Subunit ◽  
Rat Livers

Rat glutathione S-transferase (GST) subunit 3 gene has polymorphism, one type encoding Asn198-Cys199 (NC type) and another encoding Lys198-Ser199 (KS type). To examine whether the two types of GST 3-3 exhibit different susceptibilities to oxidative stress in vivo, rats were administered with CCl4, a hepatotoxin causing severe oxidative stress, and its effect on liver GST 3-3 was compared. Decrease in GST activities in liver due to CCl4 administration was more evident in NC type rats than in KS type rats, and most GST activities of KS type rats were confined to S-hexylglutathione–Sepharose, whereas those of NC type rats were not. Decreases in GST subunits 1 and 3 were more marked in NC type rats and glutathiolated NC type GST 3-3 was also detected. These results indicated that KS and NC type GST 3-3 of rat livers exhibited different susceptibilities to CCl4in vivo. A protein consisting of a subunit with molecular mass of 90 kDa was shown to bind to KS type GST 3-3 but not to NC type. This protein was identified as heat-shock protein (HSP) 90β by N-terminal amino acid sequencing and immunoblotting. A specific HSP90 inhibitor geldanamycin released their binding. There was no difference in the binding of apoptosis signal-regulating kinase 1 to GST 3-3 between NC and KS type rats. These findings suggest that HSP90 interacts with KS type GST 3-3 and thereby protects it from inactivation due to CCl4.

Glycyrrhizin effects rat hepatocytes via the reduction of heat shock protein 90 expression

2001 ◽  
Vol 120 (5) ◽  
pp. A357-A357
Author(s):  
T YOH ◽  
T NAKASHIMA ◽  
Y SUMIDA ◽  
Y KAKISAKA ◽  
H ISHIKAWA ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 90 ◽  
Rat Hepatocytes
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