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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have isolated a full length cDNA that encodes a heat shock protein, hsp90, from a rat brain library and present the nucleotide sequence and deduced amino acid sequence. Comparison of the entire nucleotide sequence with mouse hsp84 and human hsp90 beta cDNAs reveal sequence similarities of 92 and 87%, respectively. The coding region of 2172 nucleotides corresponds to a polypeptide chain of 724 amino acids. Comparison with mouse hsp84 and human hsp90 beta amino acid sequences indicates a similarity of 97%, respectively. Characterization of the constitutive expression of this cDNA both by RNA blot hybridization and immunoblotting, reveals that it is expressed in all rat tissues examined. Hsp90 has been shown to form a transient complex with steroid hormone receptors. In order to further elucidate the role of hsp90 in the endocrine response of cells, we have examined the effects of dexamethasone and RU38486 on the level of hsp90 mRNA in a system in which glucocorticoids down-regulate glucocorticoid receptor mRNA levels. In this system, a subtle but reproducible approx. 2-fold decrease in hsp90 mRNA levels is observed after 48 h treatment with dexamethasone.
J Steroid Biochem Mol Biol 1992 Sep
PMID:Cloning and regulation by glucocorticoid receptor ligands of a rat hsp90. 152 42

The regulation of heat shock protein 90 kDa (hsp90) by estradiol was analyzed in the rat ventromedial hypothalamus (VMH) and uterus by one-dimensional gel electrophoresis/Western blots. Protein from VMH and uterus (35 micrograms/sample) was resolved on 8% acrylamide gels, transferred to polyvinyldifluoride filters, and processed for immunoblotting using an anti-hsp90 antibody. Hsp90-specific bands were visualized on film using enhanced chemiluminescence and quantitated using a laser scanning densitometer. Hsp90 protein levels were significantly elevated in VMH at 12 h (p less than 0.01), and in uterus at 18 h (p less than 0.05) following estradiol injection (10 micrograms, s.c.). Immunocytochemical analysis for hsp90 localization by cell types showed that, in brain, hsp90 immunoreactivity was primarily neuronal. In the uterus, hsp90 immunoreactivity was most evident following treatment with estradiol, and was found primarily in the glandular epithelia; staining was less prominent in myometrium, stroma, and in the luminal epithelium. Thus, increased hsp90 levels may mediate some cellular responses to estrogen in specific cell types in both uterus and brain.
Mol Cell Endocrinol 1992 Apr
PMID:Estrogenic regulation of heat shock protein 90 kDa in the rat ventromedial hypothalamus and uterus. 158 90

A comparison of HSP84 and HSP86 mRNA expression in adult mouse tissues revealed distinct expression patterns for these highly homologous genes. Particularly striking is the germ cell specificity of HSP86 expression in the testis, suggesting distinct roles for HSP84 and HSP86 with respect to testicular function and development.
Mol Cell Biol 1990 Jun
PMID:Expression of HSP86 in male germ cells. 234 73

Ten to twelve copies of the 83-kDa heat-shock protein gene (hsp83) from Trypanosoma brucei are arranged in a head-to-tail tandem array of 2.8-kb repeat units, which are transcribed to give 2.6-kb mature mRNAs. We have cloned and sequenced one of the repeat units. The gene encodes a putative protein of 81 kDa which is highly homologous to Hsp83 of Drosophila melanogaster (75%), Hsp90 of Saccharomyces cerevisiae (72%) and the C62.5 protein of Escherichia coli (61%). The 5' end of the mature mRNA was mapped by primer extension sequence analysis and shown to contain the spliced leader. The mapping of the 3' poly(A) addition sites by S1 analysis indicated that there is 218 nt of intergenic sequence linking the boundaries encoding the mature mRNA. Within this sequence are a number of elements conserved with the trypanosome hsp70 intergenic region, including a 14-nt sequence that also has homology to the Drosophila heat-shock consensus element.
Mol Biochem Parasitol 1989 Nov
PMID:A transcriptional analysis of the Trypanosoma brucei hsp83 gene cluster. 251 34

Murine uterine steady-state protein levels of the 90-kilodalton heat shock protein (HSP90) have been demonstrated recently to be increased by estrogen in a target tissue- and steroid-specific manner (C. Ramachandran, M.G. Catelli, W. Schneider, and G. Shyamala, Endocrinology 123:956-961, 1988). We now report that this regulation occurred with both the HSP86 and HSP84 forms of HSP90 as well as with the 94-kilodalton glucose-regulated protein. At the mRNA level, this response was greatest for HSP86 (15-fold). In contrast, estradiol had no significant effect on HSP70.
Mol Cell Biol 1989 Aug
PMID:Estrogenic regulation of murine uterine 90-kilodalton heat shock protein gene expression. 279 99

Hsp83 is the Drosophila homolog of the mammalian Hsp90 family of regulatory molecular chaperones. We show that maternally synthesized Hsp83 transcripts are localized to the posterior pole of the early Drosophila embryo by a novel mechanism involving a combination of generalized RNA degradation and local protection at the posterior. This protection of Hsp83 RNA occurs in wild-type embryos and embryos produced by females carrying the maternal effect mutations nanos and pumilio, which eliminate components of the posterior polar plasm without disrupting polar granule integrity. In contrast, Hsp83 RNA is not protected at the posterior pole of embryos produced by females carrying maternal mutations that disrupt the posterior polar plasm and the polar granules--cappuccino, oskar, spire, staufen, tudor, valois, and vasa. Mislocalization of oskar RNA to the anterior pole, which has been shown to result in induction of germ cells at the anterior, leads to anterior protection of maternal Hsp83 RNA. These results suggest that Hsp83 RNA is a component of the posterior polar plasm that might be associated with polar granules. In addition, we show that zygotic expression of Hsp83 commences in the anterior third of the embryo at the syncytial blastoderm stage and is regulated by the anterior morphogen, bicoid. We consider the possible developmental significance of this complex control of Hsp83 transcript distribution.
Mol Cell Biol 1993 Jun
PMID:Dynamic Hsp83 RNA localization during Drosophila oogenesis and embryogenesis. 768 2

Hsp90 is a protein chaperone whose functions are focused on a specific set of target proteins. The nature of Hsp90's interactions with these proteins is poorly understood. To provide tools for examining these interactions, we have isolated eight broadly distributed temperature-sensitive (ts) point mutations in the Hsp90 gene (HSP82) of Saccharomyces cerevisiae. The mutants fall into two distinct classes. One has a classic ts phenotype, with nearly wild-type activity at 25 degrees C and a precipitous loss of function at 34 degrees C. The remaining seven mutants, in contrast, cause a general reduction in Hsp90 function and are ts because they do not provide the high level of function required for growth at high temperatures. The effects of these mutants on two target proteins, a transcription factor (glucocorticoid receptor) and a tyrosine kinase (pp60v-src), provided several insights on Hsp90 function. First, Hsp90 is not only required to help the glucocorticoid receptor achieve a hormone-activable state, it is continuously required to maintain that state. Second, Hsp90's function in the maturation of pp60v-src involves separable roles in protein accumulation and kinase activation. Thus, Hsp90 is an integral component of both the steroid receptor and kinase signaling pathways. Finally, all eight point mutants affect the activation of both the glucocorticoid receptor and pp60v-src, indicating that Hsp90 promotes the activity of these very different target proteins through common mechanisms.
Mol Cell Biol 1995 Jul
PMID:Mutational analysis of Hsp90 function: interactions with a steroid receptor and a protein kinase. 779 97

The non-activated 9S forms of several steroid hormone receptors are heterooligomeric complexes consisting of the aporeceptor and three heat shock proteins, hsp90, hsp70 and hsp56. Hsp90 appears to play a facilitatory role in high-affinity steroid binding and to promote the efficacy of steroid actions on target tissues. Circulating glucocorticoid levels have a major regulatory impact on the binding capacity of hippocampal and hypothalamic corticosteroid receptors, a phenomenon that affects the activity of the hypothalamic-pituitary-adrenal axis and neuronal excitability in general. This study demonstrates that hsp90 mRNA is present in substantial amounts in hippocampal and hypothalamic areas characterized by high densities of corticosteroid receptors, and in the thymus. Steady-state levels of hsp90 mRNA in these regions were altered by chronic changes of circulating glucocorticoid concentrations in a site-specific fashion. In the hippocampus, mRNAs coding for hsp90 and both types of corticosteroid receptors (type I, MR and type II, GR) displayed a coordinate increase following adrenalectomy and castration (ADX/GX); in the hypothalamus only hsp90 mRNA levels were elevated, and none of the parameters studied was affected in the thymus by steroid hormone deprivation. Supplementation of ADX/GX rats with various doses of corticosterone in vivo elicited differential responses. Moderate elevation of circulating corticosterone levels normalized ADX/GX-increased hsp90 mRNA concentrations in the hippocampus and the hypothalamic paraventricular nucleus (PVN); this was associated with similar changes in GR and MR mRNA levels in the hippocampus, while GR mRNA concentrations in the PVN were not altered.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1994 Jul
PMID:Regulation of HSP90 and corticosteroid receptor mRNA by corticosterone levels in vivo. 795 98

In hypotonic cell extract (cytosol), unliganded progesterone receptor (PR) is known to form an oligomeric complex with heat shock protein 90 (hsp90), and this complex does not bind to DNA. Since ligand binding has been shown to render the complex less stable in vitro, it has been proposed that ligand binding regulates DNA binding and receptor activity in vivo by altering the stability of the oligomeric complex. However, there is no direct evidence as to whether this oligomeric complex is present in vivo. The present study addressed this problem. First, we used an immunoelectron-microscopic technique and monoclonal antibodies to ascertain the location of PR and hsp90 in chick oviduct cells. Hsp90 was found in the cytoplasm and PR in the nucleus. To study the relative affinities of the PR and hsp90 antibodies, we then constructed a chimeric protein (PR-hsp90), which was expressed in the HeLa cells. Both hsp90 and PR antigens of the chimera were detected in the nuclei with the same intensity, which indicates that the antibodies have equal sensitivities in detecting their antigens. This suggests that if significant amounts of nuclear hsp90 were present in intact cells, it should have been detected by our method. Our results indicate that the PR does not exist in vivo as an oligomeric, nonDNA-binding form in the cell nuclei and that the oligomeric form found in tissue extracts is possibly formed during tissue processing.
J Steroid Biochem Mol Biol 1994 Apr
PMID:Progesterone receptor and hsp90 are not complexed in intact nuclei. 818 Jan 8

The dependence of hormone binding to glucocorticoid receptors (GRs) on cellular ATP levels led us to propose that GRs normally traverse an ATP-dependent cycle, possibly involving receptor phosphorylation, and that without ATP they accumulate in a form that cannot bind hormone. We identified such a form, the null receptor, in ATP-depleted cells. GRs are basally phosphorylated, and become hyperphosphorylated after treatment with hormone (but not RU486). In mouse receptors we have identified 7 phosphorylated sites, all in the N-terminal domain. Most are on serines and lie within a transactivation region. The time-course of hormone-induced hyperphosphorylation indicates that the primary substrates for hyperphosphorylation are the activated receptors; unliganded and hormone-liganded nonactivated receptors become hyperphosphorylated more slowly. After dissociation of substrates for hyperphosphorylation are the activated receptors; unliganded and hormone-liganded nonactivated receptors become hyperphosphorylated more slowly. After dissociation of hormone, most receptors appear to be recycled and reutilized in hyperphosphorylated form. From these and related observations, we have concluded that the postulated ATP-dependent cycle can be accounted for by hormone-induced or spontaneous dissociation of receptor-Hsp90 complexes, followed by reassociation of unliganded receptors with Hsp90 via an ATP-dependent reaction like that demonstrated in cell-free systems. Other steroid hormone receptors might traverse a similar cycle. Four of the 7 phosphorylated sites in the N-terminal domain are in consensus sequences for p34cdc2 kinases important in cell cycle regulation. This observation, along with the known cell cycle-dependence of sensitivity to glucocorticoids and other evidence, point to a role for receptor phosphorylation in controlling responses to glucocorticoids through the cell cycle.
J Steroid Biochem Mol Biol 1993 Dec
PMID:Glucocorticoid receptors: ATP-dependent cycling and hormone-dependent hyperphosphorylation. 827 39


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