Interaction of hsp90 with steroid receptors: organizing some diverse observations and presenting the newest concepts

Pratt, William B.

doi:10.1016/0303-7207(90)90198-h

Cited by 124 publications

(58 citation statements)

References 43 publications

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“…This has been regarded as evidence that the ligand induces dissociation of hsp9O from receptors (8,(30)(31)(32) lysate as a source for hsp90 (33)(34)(35). Taken together, the histochemical and biochemical results suggest that PR released from the nucleus during tissue fractionation associates with cytoplasmic hsp90 and that this association is affected by the ligand.…”

Section: Discussionsupporting

confidence: 48%

Nuclear progesterone receptor is mainly heat shock protein 90-free in vivo.

Tuohimaa¹,

Pekki²,

Bläuer³

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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Heat shock protein 90 (hsp90) is associated with many steroid receptors in tissue homogenates. It is widely accepted that hsp90 regulates the binding of the receptor to the corresponding gene regulatory element. However there is no unequivocal evidence that steroid receptor-hsp90 complexes are present in the intact cells. We demonstrate here the absence of progesterone receptor (PR)-hsp90 complexes in intact target cell nuclei, using immunohistochemical and biochemical methods to determine the location and composition of the nonliganded (aporeceptor) and liganded (holoreceptor) PR complexes. In the chicken oviduct ceUls, both apo-and holoreceptors were nuclear, while hsp90 was exdusively cytoplasmic.

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Section: Discussionsupporting

confidence: 48%

Nuclear progesterone receptor is mainly heat shock protein 90-free in vivo.

Tuohimaa¹,

Pekki²,

Bläuer³

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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“…The purification scheme of Chen and coworkers included an ammonium-sulphate-precipitation step which would have separated HCR activity from hsp90 [24]. However, since hsp90 is known to associate with proteins as a dimer (reviewed in [29]), a difference larger than that observed, approximately 110 kDa, would have been expected. Fig.…”

Section: Purification Of Mk and Comparison With Hcrmentioning

confidence: 98%

Purification and characterisation of an initiation‐factor‐2 kinase from uninduced mouse erythroleukaemia cells

Mellor

Price

Oldfield

et al. 1993

European Journal of Biochemistry

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Mouse erythroleukaemia (MEL) cells, which have not been induced into erythroid development, contain a protein kinase (MKJ which phosphorylates the a subunit of protein-synthesis-initiation factor 2 (eIF-2a). In this paper, we show that this kinase phosphorylates both eIF-2a and a synthetic peptide based on the phosphorylation site in eIF-2a at Ser51, the target residue for other eIF-2a kinases. Consistent with this, prior treatment of eIF-2 with MK,, impaired the exchange of bound GDP for GTP which is catalysed by the exchange factor eIF-2B.Using a modified cell-free translation system, we have shown that MK, inhibits translation, consistent with the above observations concerning the site of phosphorylation and the effect of phosphorylation on eIF-2B-mediated guanine-nucleotide exchange.MK, has been purified and its properties have been compared with those of the haem-controlled repressor eIF-2a kinase (HCR) from rabbit reticulocytes. Its behaviour on gel filtration is similar to that of HCR, while its behaviour on anion exchange resembles that of certain phosphurylated species of HCR. Highly purified preparations of MK,, contain a protein with an apparent molecular mass of 98 kDa which comigrates with HCR on SDSDAGE. This protein undergoes phosphorylation when incubated in the presence of Mg2+-ATP, and both this apparent autophosphorylation and the activity of the kinase against eIF-2a are inhibited by the same, low, (10pM) concentrations of haemin. Phosphorylation of the 98-kDa components present in the MEL-cell kinase preparation and in purified rabbit reticulocyte HCR occurs on serine and threonine residues. Analysis of these phosphoproteins by peptide mapping reveals significant differences in their structures, indicating that they may be closely related, but are certainly not identical.Eukaryotic initiation factor 2 (eIF-2) mediates the binding of the initiator tRNA (fMet-tRNAJ to the 40s ribosomal subunit in eukaryotic cells [l]. It does so in the form of a complex which also contains GTP, which is subsequently hydrolysed to GDP prior to the binding of the 60s subunit. eIF-2 is therefore released from the ribosome as a complex with GDP. Since this is inactive in fMet-tRNA, binding, the GDP must be exchanged for GTP. This process has been termed recycling and is catalysed by a further protein factor, the guanine-nucleotide-exchange factor (eIF-2B) [2].It is well-established that phosphorylation of the a subunit of eIF-2 (eIF-2a) at a single serine residue (Ser51) impairs its recycling by eIF-2B, and hence leads to inhibition of peptide-chain initiation (reviewed in [3]). This regulatory mech- Abbreviations. dsI, double-stranded RNA-activated inhibitor, an eIF-2a kinase ; eIF-2, eukaryotic protein-synthesis-initiation factor 2 ; eIF-2a, a subunit of eIF-2; eIF-2B, eukaryotic initiation factor 2B ; HCR, the haem-controlled repressor, an eIF-2a kinase ; hsp90, 90-kDa heat-shock protein ; MEL, mouse erythroleukaemia ; MK,, eIF-2a kinase from induced MEL cells ; M K , eIF-2a kinase from uninduced MEL cells ; f ...

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“…A precedent for ascribing a role for HSP70 in regulating nuclear uptake of NFB exists in the regulation of steroid receptor nuclear translocation (60,61,65). The glucocorticoid receptor (GR) resides in the cytosol as a large heteromeric complex containing two molecules of HSP90, and, upon hormone binding, dissociation of HSP90 allows the GR to move into the nucleus.…”

Section: Discussionmentioning

confidence: 99%

Heat Shock Protein 70 Suppresses Astroglial-inducible Nitric-oxide Synthase Expression by Decreasing NFκB Activation

Feinstein

Galea

Aquino

et al. 1996

Journal of Biological Chemistry

267

192

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In brain glial cells, expression of calcium independent nitric-oxide synthase (NOS-2) is induced following stimulation with bacterial endotoxin (lipopolysaccharide (LPS)) and/or pro-inflammatory cytokines. We have investigated the effects of heat shock (HS), which can reduce inflammatory responses in several cell types, on the induction of glial NOS-2 expression. Preincubation of cells for 20 -60 min at 43°C decreased subsequent levels of NOS-2 induction, with a maximal 80% reduction after 60 min of HS. Following HS, cells were refractory to NOS inducers for up to 4 h, after which time little or no suppression was observed. HS reduced cytosolic NOS-2 enzymatic activity (3-fold), steady state mRNA levels (2-3-fold), and gene promoter activity (by 50%). HS also reduced LPS-induced nuclear accumulation of transcription factor NFB p65 subunit, suggesting perturbation of NFB activation.A role for HS protein (HSP) 70 in NOS-2 suppression by HS is supported by the demonstration that 1) transfection with human HSP70 cDNA partially replicated HS effects; 2) antisense, but not sense, oligonucleotides directed against rat HSP70 partially blocked HS effects; and 3) rat fibroblasts stably expressing human HSP70 did not express NOS-2 in response to LPS plus cytokines. As with heat-shocked cells, HSP70-expressing cells also exhibited decreased NFB p65 subunit nuclear accumulation. These results demonstrate that in glial cells, as well as other cell types, NOS-2 induction can be modulated by the HS response, mediated at least in part by HSP70 expression.

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Interaction of hsp90 with steroid receptors: organizing some diverse observations and presenting the newest concepts

Cited by 124 publications

References 43 publications

Nuclear progesterone receptor is mainly heat shock protein 90-free in vivo.

Nuclear progesterone receptor is mainly heat shock protein 90-free in vivo.

Purification and characterisation of an initiation‐factor‐2 kinase from uninduced mouse erythroleukaemia cells

Heat Shock Protein 70 Suppresses Astroglial-inducible Nitric-oxide Synthase Expression by Decreasing NFκB Activation

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