Human papillomaviruses (HPVs) are small, non-enveloped double stranded DNA viruses that demonstrate a strict species and cell type tropism for human epithelial cells. The association between high-risk HPV types and cervical cancer is well established. Additionally, HPVs have been implicated as causes in development of several other epithelial cancer types. Increasing data indicate heat shock proteins (HSPs) including inducible HSP70 (HSP70i) are involved in the replicative cycles of different viruses including adenoviruses, polyomaviruses (PyV), and some RNA viruses. Cell-free system studies implicate HSP70i in HPV11 genome replication with E1 and E2 proteins, and there is evidence that HSP70 is involved in capsid assembly and disassembly for PyV and PV. HSP70 expression is increased in HPV16 E6/E7 gene transduced human primary keratinocytes, and frequently detected in early stage uterine cervical cancer at levels in conjunction with lesion severity. In this study we carry out analyses with

TY - JOUR. T1 - Glucose-regulated protein GRP78 is up-regulated in prostate cancer and correlates with recurrence and survival. AU - Daneshmand, Siamak. AU - Quek, Marcus L.. AU - Lin, Ed. AU - Lee, Charlotte. AU - Cote, Richard J.. AU - Hawes, Debra. AU - Cai, Jie. AU - Groshen, Susan. AU - Lieskovsky, Gary. AU - Skinner, Donald G.. AU - Lee, Amy S.. AU - Pinski, Jacek. PY - 2007/10/1. Y1 - 2007/10/1. N2 - Chemotherapy resistance is a significant contributor to treatment failure and death in men with hormone-refractory prostate cancer. One unexplored mechanism for drug resistance is the induction of stress response proteins referred to as the glucose-regulated proteins (GRPs). We sought to determine the level of expression of GRP78, the best characterized GRP in lymph node-positive prostate cancer. Archived, paraffin-embedded, radical prostatectomy specimens were obtained from 153 patients with lymph node-positive prostate cancer (stage D1). The level of GRP78 expression was determined by ...

The evolutionary diversity of the HSP70 gene family at the genetic level has generated complex structural variations leading to altered functional specificity and mode of regulation in different cellular compartments. By utilizing Saccharomyces cerevisiae as a model system for better understanding t …

TY - JOUR. T1 - Induction of 78kD glucose-regulated protein (GRP78) expression and redox-regulated transcription factor activity by lead and mercury in C6 rat glioma cells. AU - Qian, Yongchang. AU - Hadi Falahatpisheh, M.. AU - Zheng, Ying. AU - Ramos, Kenneth S.. AU - Tiffany-Astiglioni, Evelyn. PY - 2001/1/1. Y1 - 2001/1/1. N2 - Lead (Pb) and mercury (Hg) are widespread environmental contaminants that induce prominent neural toxicity. Although the brain is not the major Pb and Hg depot in the body, these metals preferentially accumulate in astroglia to exert toxic effects. In this study, we examined the effects of Pb acetate and HgCI2 on the expression of GRP78, a molecular chaperone in the endoplasmic reticulum (ER) that may provide cytoprotection in response to cellular stresses in the C6 rat glioma cell line. We also evaluated the DNA binding activities of several redox-regulated transcription factors in metal-treated cells. Our results showed that mRNA levels of GRP78 were up-regulated by ...

TY - JOUR. T1 - Selective depletion of inducible HSP70 enhances immunogenicity of rat colon cancer cells. AU - Gurbuxani, Sandeep. AU - Bruey, Jean Marie. AU - Fromentin, Annie. AU - Larmonier, Nicolas. AU - Parcellier, Arnaud. AU - Jäättelä, Marja. AU - Martin, François. AU - Solary, Eric. AU - Garrido, Carmen. N1 - Funding Information: We thank M Martin and B Bonnotte for valuable advice and M Moutet for excellent technical assistance. Our group is supported by a special grant from the Ligue Nationale. PY - 2001/11/8. Y1 - 2001/11/8. N2 - Expression of inducible heat shock protein 70 (HSP70) in tumor cells has been proposed to enhance their immunogenicity. However, HSP70 has also been demonstrated to prevent tumor cell death, a key process for the development of tumor cell immunogenicity. In the present study, we investigated the influence of the HSP70 protein level on PRO colon cancer cell growth and immunogenicity in syngeneic BDIX rats and nude mice. These cells have a basal expression ...

The study was aimed at assessing whether the peri-parturient period is associated with changes of intracellular and plasma inducible heat shock proteins (Hsp) 72 kDa molecular weight in dairy cows, and to establish possible relationships between Hsp72, metabolic, and immunological parameters subjected to changes around calving. The study was carried out on 35 healthy periparturient Holstein cows. Three, two, and one week before the expected calving, and 1, 2, 3, 4, and 5 weeks after calving, body conditions score (BCS) was measured and blood samples were collected to separate plasma and peripheral blood mononuclear cells (PBMC). Concentrations of Hsp72 in PBMC and plasma increased sharply after calving. In the post-calving period, BCS and plasma glucose declined, whereas plasma nonesterified fatty acids (NEFA) and tumor necrosis factor-alpha increased. The proliferative responses of PBMC to lipopolysaccharide (LPS) declined progressively after calving. The percentage of PBMC expressing CD14 ...

Heat shock proteins are generally responsible for preventing damage to proteins in response to high levels of heat. Heat shock proteins are classified into six major families based on their molecular mass: small HSPs, HSP40, HSP60, HSP70, HSP90, and HSP110. HSP60 is implicated in mitochondrial protein import and macromolecular assembly. It may facilitate the correct folding of imported proteins and may also prevent misfolding and promote the refolding and proper assembly of unfolded polypeptides generated under stress conditions in the mitochondrial matrix. HSP60 interacts with HRAS and with HBV protein X and HTLV-1 protein p40tax. HSP60 belongs to the chaperonin (HSP60) family. Note: This description may include information from UniProtKB ...

The knowledge of GRPs as molecular chaperones is rapidly evolving. It is anticipated that the GRPs will make special contributions in the areas of basic cell biology, biotechnology, and cancer biology. In particular, they may play a role as the prototype of a class of genes that are regulated by sig …

Seasonal variation in heat shock proteins Hsp70 and Hsp90 expression was studied in the leaves of two naturally growing Iris pumila populations, one inhabiting an open dune site, and the other the understorey of a Pinus silvestris stand. The Hsps were quantified by an immunoblotting procedure. The level of the Hsps was found to vary significantly both across seasons and between habitats. The mean Hsp70 concentration was significantly greater at the open area than in the woodland understorey, reaching its maximum in the summer, especially in plants experiencing full sunlight. Two Hsp90 isoforms, referred to as Hsp90a (86 kDa) and Hsp90b (84 kDa), were detected. At both habitats, the level of Hsp90a was highest in autumn, that of Hsp90b in spring, whereas both of them reached a nadir in summer. Throughout the growing season, the relative abundance of Hsp90b was higher in plants growing under vegetation canopy in comparison to those inhabiting the open dune site. An inverse relationship between the ...

The 90-kDa heat shock protein, Hsp90, was previously shown to capture firefly luciferase during thermal inactivation, thereby preventing its irreversible off-pathway aggregation and maintaining it in a folding-competent state. However, subsequent refolding of the luciferase required addition of rabbit reticulocyte lysate. Here we demonstrate that Hsc70 (cytosolic Hsp70) and Hsp40/Hdj1 (cytosolic DnaJ homologue) are the effective components in a reticulocyte lysate, while other unidentified factor in the lysate is also required for the refolding of Hsp90-captured luciferase. Though another cytosolic DnaJ homologue, Hdj2/HSDJ, was more efficient than Hsp40 in suppressing the aggregation of rhodanese, Hdj2 was less effective for the refolding of luciferase than Hsp40. In the absence of the third factor, Hsp40 could bind to the luciferase captured by Hsp90, which suggested that Hsp40 on its own was able to bind the substrate protein, but Hsc70 could not.

TY - JOUR. T1 - In vitro heat shock of human monocytes results in a proportional increase of inducible Hsp70 expression according to the basal content. AU - Vince, Rebecca V.. AU - Oliver, Katherine. AU - Midgley, Adrian W.. AU - McNaughton, Lars R.. AU - Madden, Leigh A.. PY - 2010/5. Y1 - 2010/5. KW - Heat shock. KW - Stress response. KW - Hsp70. KW - Monocytes. KW - Diurnal variation. U2 - 10.1007/s00726-009-0354-4. DO - 10.1007/s00726-009-0354-4. M3 - Article. VL - 38. SP - 1423. EP - 1428. JO - Amino Acids. JF - Amino Acids. SN - 0939-4451. IS - 5. ER - ...

Domain architectures containing both Actin-like ATPase domain and Heat shock protein 70kD (HSP70), peptide-binding domain in Thelohanellus kitauei. Links to architectures containing these domain pairs in other groups of genomes are provided. Domain pairs which are not adjacent can be added/removed.

The in vivo function of the heat shock protein 90 (Hsp90) molecular chaperone is dependent on the binding and hydrolysis of ATP, and on interactions with a variety of co-chaperones containing tetratricopeptide repeat (TPR) domains. We have now analysed the interaction of the yeast TPR-domain co-chaperones Sti1 and Cpr6 with yeast Hsp90 by isothermal titration calorimetry, circular dichroism spectroscopy and analytical ultracentrifugation, and determined the effect of their binding on the inherent ATPase activity of Hsp90. Sti1 and Cpr6 both bind with sub-micromolar affinity, with Sti1 binding accompanied by a large conformational change. Two co-chaperone molecules bind per Hsp90 dimer, and Sti1 itself is found to be a dimer in free solution. The inherent ATPase activity of Hsp90 is completely inhibited by binding of Sti1, but is not affected by Cpr6, although Cpr6 can reactivate the ATPase activity by displacing Sti1 from Hsp90. Bound Sti1 makes direct contact with, and blocks access to the ...

Hypoxia upregulated protein 1, encoded by the HYOU1 gene, belongs to the heat shock protein 70 family. It is also known as 150 kDa oxygen-regulated protein (ORP150), 170 kDa glucose-regulated protein (GRP170), glucose-regulated protein 170, and HSP12A. The HYOU1 gene is transcribed into three mRNAs, due to the use of alternative transcription sites. A segment at the 5 end of exon 1A is involved in stress-dependent induction and results in the accumulation of ORP150 in the endoplasmic reticulum under low oxygen conditions. Suppression of the HYOU1 gene is associated with accelerated apoptosis, while its upregulation is associated with tumor development and invasiveness.. ...

Eukaryotic genomes encode multiple 70-kDa heat-shock proteins (HSP70s). The Saccharomyces cerevisiae HSP70 family is comprised of eight members. Here we present the nucleotide sequence of the SSA3 and SSB2 genes, completing the nucleotide sequence data for the yeast HSP70 family. We have analyzed these yeast sequences as well as 29 HSP70s from 24 additional eukaryotic and prokaryotic species. Comparison of the sequences demonstrates the extreme conservation of HSP70s; proteins from the most distantly related species share at least 45% identity and more than one-sixth of the amino acids are identical in the aligned region (567 amino acids) among all proteins analyzed. Phylogenetic trees constructed by two independent methods indicate that ancient molecular and cellular events have given rise to at least four monophyletic groups of eukaryotic HSP70 proteins. Each group of evolutionarily similar HSP70s shares a common intracellular localization and is presumed to be comprised of functional ...

Previous studies have shown that different Hsp70 paralogs have both overlapping and diverse functions (Boorstein et al. 1994; Daugaard et al. 2007). The divergent C-terminal SBDs (substrate-binding domains) are necessary for certain co-chaperone interactions and probably define their distinctive function (Brocchieri et al. 2008; Demand et al. 1998; Sung et al. 2001). For example, cytosolic eukaryotic Hsp70s possess GGMP repeats and the EEVD motif at the carboxyl terminus, whereas other Hsp70 family members lack such structural elements (Boorstein et al. 1994; Freeman et al. 1995). It has been shown that in photosynthetic eukaryotes: (1) the Hsp70s are located in four different cell compartments: the cytoplasm, mitochondria, endoplasmic reticulum (ER), and chloroplast (Bukau and Horwich 1998; Sung et al. 2001), and; (2) the most common motif for the cytosolic is EEVD, for the endoplasmic reticulum (ER) is HDEL, for the mitochondrion is PEAEYEEAKK and for the plastid is PEGDVIDADFTDSK (Guy and Li ...

The SCOP classification for the Heat shock protein 70kD (HSP70), peptide-binding domain superfamily including the families contained in it. Additional information provided includes InterPro annotation (if available), Functional annotation, and SUPERFAMILY links to genome assignments, alignments, domain combinations, taxonomic visualisation and hidden Markov model information.

The importance of HSPs themselves in antigen presentation and cross-presentation remains controversial. Most studies agree that as part of their molecular chaperone function, HSPs can bind and present tumor associated antigens to professional antigen presenting cells through MHC class I and class II molecules, leading to the activation of anti-tumor CD8+ and CD4+ T cells. The regulation of the innate and adaptive immune responses by HSPs is still a matter of intense research. HSPs are seen as important anticancer vaccine adjuvants. They are used through different delivery systems: HSPs/antibodies, peptide/protein-HSP complexes, tumor antigen/HSP gene fusion, viral peptides/HSP complexes or gene fusion, viral proteins/bacterial HSP fusion. In preclinical models different administration routes, subcutaneous, intradermal, intramuscular or even peroral (under special conditions) can be used, and the animal toxicities are non-significant. The HSP-based vaccines can induce specific and non-specific ...

Heat shock protein 90 (Hsp90) is a well-known adenosine 5′-triphosphate (ATP)-dependent protein chaperone that achieves cellular protein homeostasis (1). A remarkable number of Hsp90 client proteins play important roles in the growth and proliferation of cancer cells (2). Beyond their effects on all the clients, kinase levels are highly correlated with the Hsp90 chaperone cycle, which makes Hsp90 an attractive anticancer therapeutic target (3). At present, the main focus of research targeting Hsp90 is competitively inhibiting the adenosine triphosphatase (ATPase) binding site on the Hsp90 N-terminal domain, leading to 17 small-molecule inhibitors with diverse structure types entered into clinical trials. However, current Hsp90 inhibitors exert a variety of toxicities (such as cardiotoxicity, gastrointestinal toxicity, and ocular toxicity) and ineluctable heat shock responses with limited clinical validity, which become the major obstacles restricting their approval to the market (4, 5). During ...

Heat shock proteins, Hsp70 chaperones help to fold many proteins. Hsp70 assisted folding involves repeated cycles of substrate binding and release. Hsp70 activity is ATP dependent. Hsp70 proteins are made up of two regions: the amino terminus is the ATPase domain and the carboxyl terminus is the substrate binding region [ (PUBMED:9476895) ]. Hsp70 proteins have an average molecular weight of 70kDa [ (PUBMED:2686623) (PUBMED:2944601) (PUBMED:3282176) ]. In most species, there are many proteins that belong to the Hsp70 family. Some of these are only expressed under stress conditions (strictly inducible), while some are present in cells under normal growth conditions and are not heat-inducible (constitutive or cognate) [ (PUBMED:2143562) (PUBMED:2841196) ]. Hsp70 proteins can be found in different cellular compartments(nuclear, cytosolic, mitochondrial, endoplasmic reticulum, for example). This entry represents the Hsp70 family, and includes chaperone protein DnaK and luminal-binding proteins. It ...

热激蛋白90（heat shock protein 90，HSP90）广泛介导了胁迫信号的传递，在控制人体细胞正常生长和促进肿瘤细胞发育中起着重要作用；目前，HSP90已成为细胞免疫、信号转导以及抗肿瘤研究的前沿课题。植物HSP90的生理功能研究起步较晚，最近的研究发现HSP90在植物发育、胁迫环境的应答以及抗病性中起着重要作用。本文从分子生物学角度，系统综述了植物HSP90分子作用机理研究的最新进展，以及在改良植物抗性上的应用，以期为通过基因工程方法改良作物抗性提供参考。;Heat shock protein 90 (HSP90) widely mediated stress signal transduction, and plays an important role in the control of normal growth of human cells and in the promoting tumor cell development. At present, HSP90 has become forefront projects of cellular immunity, signal transduction and anti-cancer investigation. The physiological function of HSP90 start later in plant than in animal and fungi

Several neuroinflammatory disorders are known or suspected to involve autoimmunity. Practically all proteomic studies of MP/exosomes detect substantial amounts of IgG, IgM, and complement (C) fragments on MP. It has long been known that MP-associated antibody-antigen (Ab:Ag) complexes (IC) are released on MP by the action of C. Recently, it was shown that MP-IC exert significant neuroinflammatory action [42]. The cause of shedding of IC from cell surfaces is often C-mediated attack on the opsonized cells, resulting in the release of Ab/Ag/C complex MP. A specific protein, mortalin, has been identified as instrumental in this process [71]. Mortalin belongs to the HSP family (stress chaperones) and has been implicated in Parkinsons disease (PD) [72]. Additional related references are given in the review by Robbins et al. [73], covering also cytokines on MP and their surface expression of PAMPs/DAMPs (pathogen-associated molecular patterns and danger-associated molecular patterns), which ...

In recent years Hsp90 is available to connect to several telomeric proteins at various phases of cell cycle. in an ATP dependent manner with several cochaperones and provides the maturation of the target protein at a near native state [4]. In budding yeast there are two isoforms of Hsp90; Hsc82 (human ortholog of Hsp90β) which is constitutively expressed in the cell and Hsp82 (human ortholog of Hsp90α) which is induced whenever cells are exposed to any kind of stressed condition. It is known that expression of either one of the two isoforms of Hsp90 is required for yeast viability [5]. The two isoforms share 97% sequence identity and they comprise (1-2) % of the total cytosolic proteins. Hsp90 level is significantly increased in the cell upon exposure to stress including temperature nonphysiological pH nutrient deprivation and malignancy [6]. Recent studies possess unraveled novel jobs of Hsp90 where Hsp90 and its own cochaperone p23 get excited about stabilization SU-5402 of different ...

A tumor-selective cell surface localization of warmth shock protein 70 (Hsp70), the major heat-inducible member of the Hsp70 group, correlates with an increased awareness to lysis mediated by individual normal killer (NK) cells and, therefore, may be of clinical relevance. surprise proteins (Hsps) have already been found to try out essential roles in cancers immunity. Members from the Hsp70 and Hsp90 family members are recognized to chaperone tumor-derived peptides to main histocompatibility complicated (MHC) course I substances to elicit an anticancer immune system response mediated by T cells (Tamura et al 1997). Hsp70, the main heat-inducible person in the Hsp70 group, continues to be detected in the cell surface area of tumor cells however, not on regular cells (Ferrarini et al 1992; Multhoff et al 1995a). This uncommon Hsp70 plasma membrane appearance correlates with an elevated level of sensitivity to allogeneic natural killer (NK) cells (Botzler et al 1996a; Botzler et al 1996b; Multhoff ...

The molecular chaperone Hsp90 plays an essential role in protein biogenesis, where it facilitates folding and suppresses aggregation, and in protein degradation, where it contributes to quality control by promoting the recognition and proteolysis of misfolded proteins. In many cell types, including ECs, Hsp90 also participates in the modulation of intracellular signaling events. Indeed, Hsp90 associates with eNOS and regulates its activity in response to endothelium-specific agonists, such as VEGF.11,12,27 Hsp90 activity is controlled by cochaperones, and AHA1 has been identified as an activator of the ATPase activity of Hsp90.20 The present study was designed to assess in ECs the role of AHA1 in the modulation of Hsp90 activity. Our data demonstrate for the first time in primary ECs that changes in AHA1 protein levels influence eNOS phosphorylation and its association with Hsp90 in response to VEGF treatment. In turn, this affects NO production, which contributes to endothelial migration, ...

Polymer-block-peptide conjugates are tailored to render hydrophobic small molecule drugs water soluble. The combinatorial strategy selects for bioconjugates that exhibit sequence-specific solubilization and switchable release profiles of the cargo through incorporation of a disulfide linker moiety into the peptide-library design. While the study focused on the photosensitizer m-THPC and reductive carrier cleavage, the approach is generic and might be expanded toward a broad range of poorly soluble small-molecule drugs and other selective cleavage mechanisms to disassemble a peptide binding domain of the bioconjugate-based solubilizer. Wieczorek, Sebastian; Vigne, Sara; Masini, Tiziana; Ponader, Daniela; Hartmann, Laura; Hirsch, Anna K. H.; Boerner, Hans G.

Title: 17 AAG for HSP90 Inhibition in Cancer - From Bench to Bedside. VOLUME: 9 ISSUE: 5. Author(s):Saad Z. Usmani, Robert Bona and Zihai Li. Affiliation:University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT 06030-1601, USA.. Keywords:17-AAG, heat shock protein 90, cancer, clinical trials. Abstract: Heat shock protein 90 (HSP90) family of proteins are ubiquitous molecular chaperones that are involved in folding, activation, maturation and assembly of many proteins that include essential mediators of signal transduction and cell cycle progression. They are abundant in eukaryotic cells and localized to the cytoplasm, mitochondria as well as the endoplasmic reticulum under normal conditions, making up 1-2% of all cellular proteins. HSP90 proteins have increased expression in a number of malignancies. A large number of HSP90 client proteins have been shown to be necessary for the development, proliferation and survival of specific types of cancers. HSP90 inhibition can ...

First, alterations in thermotolerance were linked to alterations in heat tolerance by three different types of genetic manipulation: inhibiting HSP101 expression through the production of antisense RNAs or by cosuppression of impaired thermotolerance, whereas overexpressing HSP101 enhanced it. Second, in each case, multiple independent transformants that affected HSP101 in the same way displayed the same change in thermotolerance, and no transformants that substantially affected HSP101 expression failed to affect thermotolerance. Third, in experiments in which conditions were sensitive enough to detect them, dosage relationships were apparent. Constitutive lines with the highest levels of HSP101 expression were the best able to withstand heat stress, and antisense lines with the strongest inhibition of HSP101 expression were the most severely affected by heat stress. Fourth, changes in HSP101 expression altered both acquired and basal thermotolerance.. Finally, when the effects of antisense and ...

Tah1 [TPR (tetratricopeptide repeat)-containing protein associated with Hsp (heat-shock protein) 90] has been identified as a TPR-domain protein. TPR-domain proteins are involved in protein-protein interactions and a number have been characterized that interact either with Hsp70 or Hsp90, but a few can bind both chaperones. Independent studies suggest that Tah1 interacts with Hsp90, but whether it can also interact with Hsp70/Ssa1 has not been investigated. Amino-acid-sequence alignments suggest that Tah1 is most similar to the TPR2b domain of Hop (Hsp-organizing protein) which when mutated reduces binding to both Hsp90 and Hsp70. Our alignments suggest that there are three TPR-domain motifs in Tah1, which is consistent with the architecture of the TPR2b domain. In the present study we find that Tah1 is specific for Hsp90, and is able to bind tightly the yeast Hsp90, and the human Hsp90α and Hsp90β proteins, but not the yeast Hsp70 Ssa1 isoform. Tah1 acheives ligand discrimination by ...

Heat shock protein 90 (Hsp90) is an ubiquitous molecular chaperone protein that is involved in folding, activation, and assembly of many proteins, including key mediators of signal transduction, cell cycle control, and transcriptional regulation. In cancer cells that are dependent upon Hsp90 client proteins, the degree to which clients are inhibited correlates closely with induction of growth inhibition and apoptosis with Hsp90 inhibitory drugs. The active pharmaceutical ingredient of CNF2024, CF1983 mesylate, is a synthetic, new chemical entity designed to inhibit Hsp90. CF1983 hada strong affinity for tumor derived Hsp90 and weaker affinity for Hsp90 isolated from normal cells or recombinant Hsp90 ...

Functional roles of heat shock proteins (HSP). The evolutionarily conserved molecular chaperones of the HSP70 (HSPA) family fulfill an essential role in maintai

Previously we demonstrated that Heat shock protein 27 (HSP27) has atheroprotective effects [Circ Res 2008].PURSPOSE: To determine if HSP27 may provide an effective strategy to enhance re-endothelialization of injured vessels, including stented arteries. 72 male and female wild type (WT) and HSP27 over-expressing (HSP27o/e) mice were fed a normal chow and subjected to femoral artery wire injury before being euthanized on days 7, 14 or 28. The circulating CD45dim/Sca-1+/Flk-1+ endothelial progenitor cells (EPCs) from HSP27o/e mice increased 2.8- and 2.7-fold on days 3 and 7 post injury compared to WT (p,0.05). Re-endothelialization increased by 67% and 65% in HSP27o/e males and females on day 7 relative to WT mice (e.g., males: 78.4±7.5% vs. 47.0±6.9%; females: 80.9±4.9% vs. 48.9±4.6%; p,0.05 for both sexes). By 28 days the intima:media ratio was reduced by 52% and 75% in male and female HSP27o/e mice respectively (e.g., males: 0.34±0.06 vs. 0.71±0.14 and females: 0.14±0.05 vs. 0.57±0.06; ...

Complete information for HSPA2 gene (Protein Coding), Heat Shock Protein Family A (Hsp70) Member 2, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium

Grace Salsbury*: Characterising the role of molecular chaperone systems in the defective trafficking of mutant channel complexes in the long QT syndromePlatelet transcriptomics and thrombosis, with Prof Paul ...

人Heat Shock Protein 27 ELISA试剂盒(HSP27) ELISA试剂盒datasheet (ab108862).Abcam抗体、ELISA、激动剂拮抗剂、表观遗传试剂、蛋白多肽，使用效果保证，中国70%以上现货。

Hsp90 as a capacitor for morphological evolution. A high-affinity confrontation of Hsp90 confers tumour selectivity on Hsp90 inhibitors

Hsp70 chaperones are required for key cellular processes and response to environmental changes and survival but they have not been fully characterized yet. The human hsp70-gene family has an unknown number of members (eleven counted over ten years ago); some have been described but the information is incomplete and inconsistent. A coherent body of knowledge encompassing all family components that would facilitate their study individually and as a group is lacking. Nowadays, the study of chaperone genes benefits from the availability of genome sequences and a new protocol, chaperonomics, which we applied to elucidate the human hsp70 family. We identified 47 hsp70 sequences, 17 genes and 30 pseudogenes. The genes distributed into seven evolutionarily distinct groups with distinguishable subgroups according to phylogenetic and other data, such as exon-intron and protein features. The N-terminal ATP-binding domain (ABD) was conserved at least partially in the majority of the proteins but the C-terminal

HEADER CHAPERONE 05-JUN-12 4AWP TITLE COMPLEX OF HSP90 ATPASE DOMAIN WITH TROPANE DERIVED INHIBITORS COMPND MOL_ID: 1; COMPND 2 MOLECULE: HEAT SHOCK PROTEIN HSP 90-ALPHA; COMPND 3 CHAIN: A, B; COMPND 4 FRAGMENT: ATPASE DOMAIN, RESIDUES 9-236; COMPND 5 SYNONYM: HEAT SHOCK 86 KDA, HSP 86, HSP86, RENAL CARCINOMA ANTIGEN COMPND 6 NY-REN-38, HSP90; COMPND 7 EC: 3.6.4.10; COMPND 8 ENGINEERED: YES SOURCE MOL_ID: 1; SOURCE 2 ORGANISM_SCIENTIFIC: HOMO SAPIENS; SOURCE 3 ORGANISM_COMMON: HUMAN; SOURCE 4 ORGANISM_TAXID: 9606; SOURCE 5 EXPRESSION_SYSTEM: ESCHERICHIA COLI; SOURCE 6 EXPRESSION_SYSTEM_TAXID: 562 KEYWDS CHAPERONE, INHIBITOR EXPDTA X-RAY DIFFRACTION AUTHOR J.C.LOUGHEED,T.J.STOUT REVDAT 1 29-AUG-12 4AWP 0 JRNL AUTH J.BUSSENIUS,C.M.BLAZEY,N.AAY,N.K.ANAND,A.ARCALAS,T.BAIK, JRNL AUTH 2 O.J.BOWLES,C.A.BUHR,S.COSTANZO,J.K.CURTIS,S.C.DEFINA, JRNL AUTH 3 L.DUBENKO,T.S.HEUER,P.HUANG,C.JAEGER,A.JOSHI,A.R.KENNEDY, JRNL AUTH 4 A.I.KIM,K.LARA,J.LEE,J.LI,J.C.LOUGHEED,S.MA,S.MALEK, JRNL AUTH 5 ...

HEADER CHAPERONE 05-JUN-12 4AWQ TITLE COMPLEX OF HSP90 ATPASE DOMAIN WITH TROPANE DERIVED INHIBITORS COMPND MOL_ID: 1; COMPND 2 MOLECULE: HEAT SHOCK PROTEIN HSP 90-ALPHA; COMPND 3 CHAIN: A, B; COMPND 4 FRAGMENT: ATPASE DOMAIN, RESIDUES 9-236; COMPND 5 SYNONYM: HEAT SHOCK 86 KDA, HSP 86, HSP86, RENAL CARCINOMA ANTIGEN COMPND 6 NY-REN-38, HSP90; COMPND 7 EC: 3.6.4.10; COMPND 8 ENGINEERED: YES SOURCE MOL_ID: 1; SOURCE 2 ORGANISM_SCIENTIFIC: HOMO SAPIENS; SOURCE 3 ORGANISM_COMMON: HUMAN; SOURCE 4 ORGANISM_TAXID: 9606; SOURCE 5 EXPRESSION_SYSTEM: ESCHERICHIA COLI; SOURCE 6 EXPRESSION_SYSTEM_TAXID: 562 KEYWDS CHAPERONE EXPDTA X-RAY DIFFRACTION AUTHOR J.C.LOUGHEED,T.J.STOUT REVDAT 2 28-JUN-17 4AWQ 1 REMARK REVDAT 1 29-AUG-12 4AWQ 0 JRNL AUTH J.BUSSENIUS,C.M.BLAZEY,N.AAY,N.K.ANAND,A.ARCALAS,T.BAIK, JRNL AUTH 2 O.J.BOWLES,C.A.BUHR,S.COSTANZO,J.K.CURTIS,S.C.DEFINA, JRNL AUTH 3 L.DUBENKO,T.S.HEUER,P.HUANG,C.JAEGER,A.JOSHI,A.R.KENNEDY, JRNL AUTH 4 A.I.KIM,K.LARA,J.LEE,J.LI,J.C.LOUGHEED,S.MA,S.MALEK, JRNL ...

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The heat-shock protein 90 (HSP90) family is a group of highly conserved molecular chaperones with important functions in protein folding and in signal transduction. The HSP90 protein structure is so well conserved that some HSP90 antibodies are reactive with a broad range of species from humans to chickens.

Get this from a library! Immunity, tumors and aging : the role of HSP70. [Igor Malyshev] -- The book is dedicated to the topical area of biology and medicine and the role of stress proteins HSP70 in the regulation of intracellular protein homeostasis, signaling transduction and cell ...

View mouse Hsp90b1 Chr10:86690209-86705509 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression

View mouse Hsp90ab1 Chr17:45567778-45573261 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression

JG-98, an allosteric heat shock protein 70 (Hsp70) inhibitor, which binds tightly to a conserved site on Hsp70 and disrupts the Hsp70-Bag3 interaction. JG-98 shows anti-cancer activities affecting both cancer cells and tumor-associated macrophages. - Mechanism of Action & Protocol.

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The protein encoded by this gene contains an atypical heat shock protein 70 (Hsp70) ATPase domain and is therefore a distant member of the mammalian Hsp70 family. This gene may be involved in susceptibility to atherosclerosis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015 ...

Method: Induction of HSP70B mRNA is carried out by treatment of cells with TRC051384 (6.25 and 12.5 μM) for 4 hours duration for HeLa cell line and total RNA is isolated. For all RNA samples, cDNAs are synthesized and expression of HSP70B mRNA along with expression of 18S rRNA is monitored by real-time PCR employing ABI 7000 system.. ...

HSP27, clone: STRSN, eBioscience™ 25μg; Unconjugated HSP27, clone: STRSN, eBioscience™ Primary Antibodies He to Hf

At the cellular level, the stress response involves the synthesis of a highly conserved family of heat shock proteins (Hsps). These proteins are essential for maintenance of cellular homeostasis, both in times of stress and in normal cell functioning. Some of the most abundant forms of Hsps in the cell are members of the 70 kDa family. Intracellular heat shock protein 70 (Hsp70) expression in response to proteotoxicity is a highly conserved cellular stress response, but little is known about the role of extracellular Hsp70 (eHsp70) in fish. In order to begin characterizing eHsp70 in fish, the hypothesis that an acute stressor will elevate plasma Hsp70 levels in rainbow trout (Oncorhynchus mykiss) was tested. Subsequent in vitro studies examined whether eHsp70 level was modulated by cortisol and if this involved the action of the glucocorticoid receptor (GR), a ligand-activated transcription factor. The effect of cortisol on the eHsp70 response is important to consider because this steroid is ...

The human heat-shock protein multigene family comprises several highly conserved proteins with structural and functional properties in common, but which vary in the extent of their inducibility in response to metabolic stress. We have isolated and characterized a novel human HSP70 cDNA, HSP70B cDNA, and its corresponding gene sequence. HSP70B cDNA hybrid-selected an mRNA encoding a more basic 70 kDa heat-shock protein than both the major stress-inducible HSP70 and constitutively expressed HSC70 heat-shock proteins, which in common with other heat-shock 70 kDa proteins bound ATP. The complete HSP70B gene was sequenced and, like the major inducible HSP70 gene, is devoid of introns. The HSP70B gene has 77% sequence similarity to the HSP70 gene and 70% similarity to HSC70 cDNA, with greatest sequence divergence towards the 3-terminus. The HSP70B gene represents a functional gene, as indicated by Northern-blot analysis with specific oligonucleotides, hybrid-selected translation with a specific ...

TY - JOUR. T1 - Structure and expression of the human gene encoding major heat shock protein HSP70. AU - Wu, B. AU - Hunt, C. AU - Morimoto, R. PY - 1985/2. Y1 - 1985/2. N2 - We have cloned a human gene encoding the 70,000-dalton heat shock protein (HSP70) from a human genomic library, using the Drosophila HSP70 gene as a heterologous hybridization probe. The human recombinant clone hybridized to a 2.6-kilobase polyadenylated mRNA from HeLa cells exposed to 43 degrees C for 2 h. The 2.6-kilobase mRNA was shown to direct the translation in vitro of a 70,000-dalton protein similar in electrophoretic mobility to the HSP70 synthesized in vivo. From the analysis of S1 nuclease-resistant mRNA-DNA hybrids, the HSP70 gene appears to be transcribed as an uninterrupted mRNA of 2.3 kilobases. We show that the cloned HSP70 gene contains the sequences necessary for heat shock-induced expression by two criteria. First, hamster cells transfected with a subclone containing the HSP70 gene and flanking sequences ...

Extracellular heat shock protein-90 (eHsp90) proteins, which include the membrane-bound, released and secreted forms were first cited in scientific literature late in the 70s. It was not until the recent decade that researchers began to understand the role of exported Hsp90 in normal and tumor cells. In normal cells, Hsp90 is secreted in response to tissue injury. Tumor cells, on the other hand, have managed to constitutively secrete Hsp90 for the purpose of tissue invasion. Cells abundantly store Hsp90 in their cytoplasm, insuring a sufficient supply of extracellular Hsp90 at a moments notice. A well-characterized function of secreted Hsp90α is to promote cell motility, a crucial event in both wound healing and cancer. One of the primary targets for extracellular Hsp90α is the cell surface LRP-1 receptor. The promotility activity of secreted Hsp90α resides within a fragment at the boundary between linker region and middle domain. Inhibiting Hsp90α secretion, neutralizing its extracellular ...

The ability to resolve protein members of the hsp70 multigene family by two-dimensional Western blotting permitted the characterization of antibodies which were specific in discriminating constitutively expressed hsc70 isoforms from stress-inducible hsp70 isoforms. This antibody characterization demonstrated that basal levels of hsp70 isoforms were present in the cerebellum of the control rabbit and that these were elevated following hyperthermia, whereas levels of hsc70 were similar in control and hyperthermic tissue. Multiple isoforms of hsp70 were detected but tissue-specific differences were not apparent in various organs of the rabbit. However, species differences were observed as fewer hsp70 isoforms were noted in rat and mouse. In the control rabbit, higher levels of hsc70 protein were present in neural tissues compared to non-neural tissues. Following physiologically relevant hyperthermia, induction of hsp70 was greatest in non-neural tissues such as liver, heart, muscle, spleen, and kidney

Nucleotide binding to the 70 kDa heat-shock cognate protein (Hsc70) from mung bean seeds and pig brain was investigated, as well as the clathrin uncoating activity of Hsc70 in the presence of these nucleotides. The two enzymes were found to behave identically. ATP bound to two different forms of Hsc70, with dissociation constants of 1.1±0.1 µM and 1.4±0.7 mM respectively at 25 °C. This corresponds to ΔG0´ = -34 and -16 kJ/mol respectively. From the temperature-dependence of the dissociation constant of the high-affinity site, ΔH0´ was calculated to -36±2 kJ/mol. This gives ΔS0´ = 6.7 J/mol per K. Adenosine 5´-[γ-thio]triphosphate, ADP, adenosine 5´-[β,γ-imino]triphosphate and adenosine 5´-[β,γ-methylene]triphosphate showed dissociation constants of 2.3, 11, 31 and 284 µM respectively. The order of affinities corresponded to the order of effectiveness in uncoating of pig brain coated vesicles. The implications of these findings for the mechanism of Hsc70 action are discussed. ...

TY - JOUR. T1 - A gram-negative characteristic segment in Escherichia coli DnaK is essential for the ATP-dependent cooperative function with the co-chaperones DnaJ and GrpE. AU - Sugimoto, Shinya. AU - Higashi, Chihana. AU - Saruwatari, Kozue. AU - Nakayama, Jiro. AU - Sonomoto, Kenji. PY - 2007/6/26. Y1 - 2007/6/26. N2 - We describe importance of the characteristic segment in ATPase domain of DnaK chaperone which is present in all gram-negative bacteria but is absent in all gram-positive bacteria. In vitro studies, ATPase activity, luciferase-refolding activity, and surface plasmon resonance analyses, demonstrated that a segment-deletion mutant DnaKΔ74-96 became defective in the cooperation with the co-chaperones DnaJ and GrpE. In addition, in vivo complementation assay showed that expression of DnaKΔ74-96 could not rescue the viability of Escherichia coli ΔdnaK mutant at 43 °C. Consequently, we suggest evolutionary significance for this DnaK ATPase domain segment in gram-negative bacteria ...

Results: In comparison with non-immune IgG, anti-HSC70 reduced myocardial expression of KC and MCP-1 mRNAs and proteins following I/R. Moreover, treatment with anti-HSC70 improved postischemic cardiac functional recovery (66±5.4% of baseline vs. 28±5.1% of baseline in hearts treated with non-immune IgG, p,0.01). Recombinant HSC70 induced myocardial expression of KC and MCP-1 mRNAs and proteins and caused cardiac dysfunction (72±2.6% of baseline vs. 98±3.9% of baseline in perfusion controls, p,0.001) in hearts with competent TLR4 (C3H/HeN). Interestingly, these effects of HSC70 were abrogated in hearts with defective TLR4 (C3H/HeJ). The potency of HSC70 was completely lost in the absence of its substrate-binding domain.. Conclusions: Taken together, our studies demonstrate, for the first time, that HSC70 plays an important role in the induction of myocardial chemokines and cardiac dysfunction during I/R. The effect of HSC70 is dependent on TLR4 and requires the presence of the ...

TY - JOUR. T1 - Domain:domain interactions within Hop, the Hsp70/Hsp90 organizing protein, are required for protein stability and structure. AU - Carrigan, Patricia E.. AU - Sikkink, Laura A.. AU - Smith, David F.. AU - Ramirez-Alvarado, Marina. N1 - Copyright: Copyright 2008 Elsevier B.V., All rights reserved.. PY - 2006/3. Y1 - 2006/3. N2 - The major heat shock protein (Hsp) chaperones Hsp70 and Hsp90 both bind the co-chaperone Hop (Hsp70/Hsp90 organizing protein), which coordinates Hsp actions in folding protein substrates. Hop contains three tetratricopeptide repeat (TPR) domains that have binding sites for the conserved EEVD C termini of Hsp70 and Hsp90. Crystallographic studies have shown that EEVD interacts with positively charged amino acids in Hop TPR-binding pockets (called carboxylate clamps), and point mutations of these carboxylate clamp positions can disrupt Hsp binding. In this report, we use circular dichroism to assess the effects of point mutations and Hsp70/Hsp90 peptide ...

Heat shock proteins (HSPs) are endogenous proteins whose function is to maintain the cells tolerance to insult, and glutamine supplementation is known to increase HSP expression during intense exercise. Since few studies have addressed the possibility that supplementation with other amino acids could have s

Heat shock protein 72 (HSP72) is expressed in response to stress and has been demonstrated to follow a diurnal expression pattern within monocytes and is sensitive to changes in core temperature. Numerous studies have shown changes in HSP72 expression within cell lines exposed to hyperbaric conditions. No studies have investigated changes in HSP72 expression in vivo. Six males participated in the study and were exposed to hyperbaric air and hyperbaric oxygen a week apart. Monocyte HSP72 was analyzed by flow cytometry at 09:00, 13:00, 17:00, 21:00 with hyperbaric oxygen or hyperbaric air breathing commencing at 15:00 for 78 min at a pressure of 2.8 ATA. HSP72 under normoxia followed the established trend; however, following the hyperbaric air or oxygen exposure a reduction in detectable HSP72 was observed at 17:00 and 21:00. No changes in core temperature were observed between 13:00 and 21:00 for any condition. The data show that HSP72 expression is impaired following hyperbaric air (HA) exposure, when

Heat shock proteins (HSPs) are ubiquitous in living organisms. HSPs are an essential component for cell growth and survival; the main function of HSPs is controlling the folding and unfolding process of proteins. According to molecular function and mass, HSPs are categorized into six different families: HSP20 (small HSPS), HSP40 (J-proteins), HSP60, HSP70, HSP90, and HSP100. In this paper, improved methods for HSP prediction are proposed—the split amino acid composition (SAAC), the dipeptide composition (DC), the conjoint triad feature (CTF), and the pseudoaverage chemical shift (PseACS) were selected to predict the HSPs with a support vector machine (SVM). In order to overcome the imbalance data classification problems, the syntactic minority oversampling technique (SMOTE) was used to balance the dataset. The overall accuracy was 99.72% with a balanced dataset in the jackknife test by using the optimized combination feature SAAC+DC+CTF+PseACS, which was 4.81% higher than the

Since the discovery of gp96 in the 1980s as a tumor rejection antigen, Heat Shock Proteins (HSPs) have received attention from immunologists for their ability to prime immune responses. Originally known for their important intracellular roles as chaperones to newly synthesized, misfolded, and/or recently degraded proteins, it is now understood that HSPs released into the extracellular environment can also initiate immune responses. Shown both in vitro and in vivo, HSPs act on antigen presenting cells (APC) to 1) deliver antigenic peptides for presentation by both MHC class I and class II molecules and 2) activate APC to increase expression of co-stimulatory molecules. Both of these activities contribute to productive T cell responses, which has led to current trials using HSP-peptide complexes as cancer vaccines. However, the cell populations responsible for monitoring exogenous HSPs and priming resulting immune responses have yet to be fully characterized. This study identifies the cells ...

This gene encodes a member of the DnaJ or Hsp40 (heat shock protein 40 kD) family of proteins. DNAJ family members are characterized by a highly conserved amino acid stretch called the J-domain and function as one of the two major classes of molecular chaperones involved in a wide range of cellular events, such as protein folding and oligomeric protein complex assembly. The encoded protein is a molecular chaperone that stimulates the ATPase activity of Hsp70 heat-shock proteins in order to promote protein folding and prevent misfolded protein aggregation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015 ...

Current models derived from in vitro studies propose that sHsps prevent irreversible substrate aggregation by binding heat-denatured substrates, and then present substrate to other cellular components for ATP-dependent refolding (Waters et al., 1996; Ehrnsperger et al., 1997;Lee et al., 1997; Veinger et al., 1998). Our data extend this model for sHsp chaperone activity in several important ways. First, we determined that the chaperones required for high levels of refolding of Hsp18.1-bound Luc were Hsp/Hsc70 plus DnaJ homologs. The addition of Hsp90 and Hop gave minimal or no further enhancement of refolding. Despite the eukaryotic origin of Hsp18.1, the highest Luc refolding rates were observed when Hsp18.1-bound Luc was reactivated in the presence of the prokaryotic DnaK system. These findings imply that the mechanism of sHsp action in conjunction with Hsp70 systems is universal among eukaryotes and prokaryotes, and suggest that sHsps may not physically interact with the Hsp70 systems. Also, ...

The ARG1 gene is predicted to encode a 410-aa polypeptide with a molecular mass of 45.5 kDa (Fig. 3A). Database searches revealed that the NH2 terminus shares strong sequence similarity with the highly conserved J domain of DnaJ-like molecular chaperone proteins found in prokaryotes and eukaryotes (Fig. 3 A and B; refs. 49-53). DnaJ-like proteins are involved in a variety of processes including protein folding, protein partitioning into organelles, signal transduction, and targeted protein degradation (54). The J domain has been shown to interact directly with Hsp70, thereby regulating its ATPase activity, which affects protein binding and folding. The Saccharomyces cerevisiae DnaJ-like protein YDJ1, together with Hsp70 and Hsp90, participates in a number of signal-transduction pathways involving steroid hormones as well as tyrosine kinases and serine-threonine kinases (55). Interestingly, these heteroligomeric complexes bind actin filaments in a Ca2+/calmodulin-regulated manner (56).. Computer ...

DNAJC4 (DnaJ heat shock protein family (Hsp40) member C4), Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol.

DNAJC21 (DnaJ heat shock protein family (Hsp40) member C21), Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol.

In the current investigation, we focused on Mortalin/mthsp70/GRP75, a member of the heat shock protein (Hsp) 70 family, which is enriched in human cancer cells [4, 9, 13]. It has been established that Mortalin has various subcellular localizations, interacts with multiple binding partners, and plays a role in carcinogenesis. Also, it is elevated in immortalized cell lines and tumor cells, and additional upregulation of Mortalin expression at later stages of carcinogenesis coincides with the acquisition of invasiveness [4]. Moreover, it has multiple functions contributing to continued proliferation of cancer cells, including mitochondrial-biogenesis, ATP production, anti-apoptosis, chaperoning, inactivation of tumor suppressor p53 and PI3K/AKT activities [14, 15]. Targeting Mortalin by siRNA, ribozymes and small molecules including MKT-077 and Withaferin A resulted in growth arrest/apoptosis of cancer cells [16-22].. Here, we confirmed that the level of Mortalin was elevated in breast cancer, ...

1NGA: Structural basis of the 70-kilodalton heat shock cognate protein ATP hydrolytic activity. II. Structure of the active site with ADP or ATP bound to wild type and mutant ATPase fragment.

International Journal of Inflammation is a peer-reviewed, Open Access journal that publishes original research and review articles on the molecular basis, cell biology and pharmacology of inflammation, including acute/chronic inflammation, mediators of inflammation, as well as cellular processes and molecular mechanisms involved in the production of inflammatory responses. The journal especially welcomes the submission of articles on anti-inflammatory drug development, trials and therapies.

Authors: Sghaier, Haïtham , Ai, Thuy Le Huyen , Horiike, Tokumasa , Shinozawa, Takao Article Type: Research Article Abstract: Molecular chaperones are a wide group of unrelated protein families whose role is to assist others proteins. Comparably, under environmental stress, stress proteins behave as biocatalysts of protein stabilization. Stress proteins include a large class of proteins that were originally termed heat shock proteins (HSPs) due to their initial discovery in tissues exposed to elevated temperatures. Many, but not all, stress proteins and HSPs are molecular chaperones. Moreover, not all HSPs are derivable from stress. HSPs …are structurally diversified by the contribution of various domains having specific roles. HSPs have been grouped, mainly on the basis of their molecular masses, into specific families that include small HSPs (sHSPs)/α-crystallins, HSP10s, HSP40s, HSP60s, HSP70s, HSP90s, HSP100s and HSP110s. The names of these major families are historical artefacts with ...

This gene is a member of the J protein family. J proteins function in many cellular processes by regulating the ATPase activity of 70 kDa heat shock proteins. This gene is a member of the type 2 subgroup of DnaJ proteins. The encoded protein is localized to the endoplasmic reticulum. This protein is induced by endoplasmic reticulum stress and plays a role in protecting stressed cells from apoptosis. [provided by RefSeq, Dec 2010 ...

The major heat shock protein 72 (Hsp72) is constitutively expressed at high levels in many human cancers, suggesting its importance in carcinogenesis. Elevated levels of Hsp72 correlate with poor prognosis, metastasis, and resistance to chemotherapy. Previous work from our laboratory with human cancer cell lines demonstrated that cancer cells became addicted to high level of Hsp72 because depletion of this protein triggered either apoptosis or senescence. Here we addressed two questions: (1) Are Hsp72 and its transcriptional regulator HSF1 critical for tumor development? (2) How does Hsp72 function in tumorigenesis? Accordingly, we generated transgenic mice that expressed the Her2 oncogene predominantly in mammary epithelial cells in Hsp72 knockout background. We also constructed mice that similarly expressed Her2 in the background of knockout of HSF1, the major transcription factor that controls the transcription of Hsp72 and other heat shock proteins. Knockout of HSF1 or Hsp72 did not have a ...

Alzheimers disease (AD) is the most prevalent neurodegenerative pathology in the growing population of elderly humans and leads eventually to dementia and death. Despite tremendous efforts, no effective treatment for AD is currently available. The severity of cognitive impairment in patients with AD usually correlates with the extent of the observed abnormality of neurons, including the quantity of neurofibrillary tangles, the decrease in synaptic density, the enhanced concentration of soluble Aβ-amyloid oligomers, and the amount of neurons that die by apoptosis (1). Heat shock proteins (Hsps) have emerged as critical regulators of neurodegenerative processes associated with protein misfolding in the brains of AD patients (2). Various data suggest that Hsp70 and other molecular chaperones function as a complex neuroprotective system, which fails in the brains of AD patients. Hsp70 confer protection against oxidative stress and inflammation which play a major role in many age-related ...

Heat shock proteins are synthesized in response to increased growth temperatures and other stress factors in virtually all organisms. The analysis of the molecular mechanism of Hsps has so far been focused mostly on the ATP‐dependent Hsp70 and GroE families, whereas the function of the members of the ATP‐independent group of small Hsps is still poorly understood.. While the expression of Hsps is ubiquitous and a similar set of proteins is produced from prokaryotes to mammals, the importance and apparent function of the different Hsps seem to vary in different organisms (Parsell and Lindquist, 1994). In yeast, thermotolerance is conveyed predominantly by Hsp104, whereas in Drosophila Hsp70 seems to be the important factor. Finally, GroE is essential for protein folding in prokaryotes and organelles; however, a functional counterpart seems to be lacking in the eukaryotic cytosol, since the structurally related TCP‐1 complex appears to be restricted to actin and tubulin folding (Lewis et al., ...

The 60 kDa heat shock protein (HSP60) has been reported to influence T-cell responses in two ways: as a ligand of toll-like receptor 2 signalling and as an antigen. Here we describe a new mechanism of T-cell immuno-regulation focused on HSP60: HSP60 is up-regulated and presented by activated T cells (HSP60 is an ergotope) to regulatory (anti-ergotypic) T cells. Presentation of HSP60 by activated T cells was found to be MHC-restricted and dependent on accessory molecules - CD28, CD80 and CD86. Anti-ergotypic T cells responded to T-cell HSP60 by proliferation and secreted IFNγ and TGFβ1. In vitro, the anti-ergotypic T cells inhibited IFNγ production by their activated T-cell targets. In vivo, adoptive transfer of an anti-ergotypic HSP60-specific T-cell line led to decreased secretion of IFNγ by arthritogenic T cells and ameliorated adjuvant arthritis (AA). Thus, the presentation of HSP60 by activated T cells turns them into targets for anti-ergotypic regulatory T cells specific for HSP60. ...

The administration of the H2O2-specific scavenger catalase attenuated the generation of apoptosis by the antitumor drugs etoposide, camptothecin, doxorubicin, and cisplatin in U-937 human promonocytic cells. By contrast, the antioxidant potentiated the generation of apoptosis by the inducers of the stress response, heat shock and cadmium, in this and other myeloid cell types. Catalase also increased the heat shock-provoked stimulation of caspase-3 and -9 activities, as well as the release of cytochrome c from mitochondria to the cytosol. The potentiation of cell death by catalase correlated with its capacity to inhibit the stress response, as demonstrated by the suppression of 70- or 27-kDa heat-shock protein expression and the inhibition of heat-shock transcription factor 1 binding activity. Conversely, the toxicity of catalase plus heat shock was attenuated when the cells were preconditioned with a soft heating, which elevated the 70-kDa heat-shock protein levels. By contrast with catalase, ...

TY - JOUR. T1 - HSP40 binding is the first step in the HSP90 chaperoning pathway for the progesterone receptor. AU - Patricia Hernández, M.. AU - Chadli, Ahmed. AU - Toft, David O.. PY - 2002/4/5. Y1 - 2002/4/5. N2 - The progesterone receptor (PR) can be isolated in its native conformation able to bind hormone, yet its ligand-binding domain rapidly loses its activity at elevated temperature. However, an in vitro chaperoning system consisting of five proteins (HSP40, HSP70, HOP, HSP90, and p23) with ATP is capable of restoring this function. The first step of this chaperoning mechanism is usually thought to be the binding of HSP70 to PR. Our findings here show that the binding of HSP40 to PR is, instead, the first step. HSP40 binding occurred rapidly and was not dependent on ATP or other proteins. The stoichiometry of HSP40 to native PR in these complexes was ∼1:1. HSP40 bound specifically and with a high affinity to native PR (Kd = 77 nM). The binding of HSP40 to PR was sustained and did not ...

Magmas-like proteins have been previously implicated in tethering the J-proteins to the translocation channel (16, 17). Our results indicate that Magmas, in addition to its conserved function at human presequence translocase, regulates the distribution of individual J-proteins associated with the complex and thereby activates the translocases for neoplastic transformation under overexpressed conditions. In agreement with the idea, intrinsic overexpression of Magmas in prostate cancer and pituitary adenomas remodels the J-protein distribution at the TIM23 complex. A similar phenotype was observed upon exogenous elevation of Magmas protein levels that lead to redistribution and recruitment of J-proteins to either of the translocases, suggesting that Magmas plays a critical role in governing translocase activity. Indeed, reorganization of J-proteins at the import channel results in equivalent translocation activity for both translocases, and they play a synergistic role in the import of precursors ...

Hsp90 (heat shock protein 90) is a chaperone protein that assists other proteins to fold properly, stabilizes proteins against heat stress, and aids in protein degradation. It also stabilizes a number of proteins required for tumor growth, which is why Hsp90 inhibitors are investigated as anti-cancer drugs. Heat shock proteins, as a class, are among the most highly expressed cellular proteins across all species. As their name implies, heat shock proteins protect cells when stressed by elevated temperatures. They account for 1-2% of total protein in unstressed cells. However, when cells are heated, the fraction of heat shock proteins increases to 4-6% of cellular proteins. Heat shock protein 90 (Hsp90) is one of the most common of the heat-related proteins. The 90 comes from the fact that it weighs roughly 90 kiloDaltons. A 90 kDa protein is considered fairly large for a non-fibrous protein. Hsp90 is found in bacteria and all branches of eukarya, but it is apparently absent in archaea. Whereas ...

Inhibition of the ATPase activity of the chaperone protein HSP90 is a potential strategy for treatment of cancers. We have determined structures of the HSP90alpha N-terminal domain complexed with the purine-based inhibitor, PU3, and analogs with enhanced potency both in enzyme and cell-based assays. The compounds induce upregulation of HSP70 and downregulation of the known HSP90 client proteins Raf-1, CDK4, and ErbB2, confirming that the molecules inhibit cell growth by a mechanism dependent on HSP90 inhibition. We have also determined the first structure of the N-terminal domain of HSP90beta, complexed with PU3. The structures allow a detailed rationale to be developed for the observed affinity of the PU3 class of compounds for HSP90 and also provide a structural framework for design of compounds with improved binding affinity and drug-like properties ...

The emergence of complementary electrostatic potentials after the prokaryotic-to-eukaryotic split drives physical and functional cooperation between canonical class A and class B J-proteins to boost protein disaggregation.

In the present study, we have shown that long-term administration of Ang II increases expression of HSP70 and HSP25, as well as HSP32 (HO-1), in the rat kidney. Losartan completely blocked Ang II-induced upregulation of all 3 HSPs. On the other hand, hydralazine completely blocked Ang II-induced HO-1 upregulation but failed to block Ang II-induced upregulation of HSP70 or HSP25, which suggested that different mechanisms may regulate Ang II-induced HO-1 upregulation compared with renal HSP70 and HSP25 induction in the kidney. Interestingly, NE did not alter expression of these HSPs, suggesting that hypertension alone was not a sufficient stimulus to increase renal expression of these HSPs.. We found that HSP70 is upregulated in the rat kidney with long-term infusion of Ang II but not NE. Xu et al18 have previously reported that HSP70 was induced in the rat kidney after bolus vasopressin injection. They also showed that vasopressin-induced upregulation of renal HSP70 is a pressor-independent ...

In field trials, heat-exposed chickens given Actigen®, a second generation mannan oligosaccharide (MOS) from Saccharomyces cerevisiae, maintained good intestinal health and performance. This investigation explored the influence of Actigen® on heat shock protein (HSP) responses in Ross 708 broiler chickens. Gender-segregated broilers were given either a control or Actigen®-supplemented (800 g/ton in starter, 400 g/ton in grower and 200 g/ton in finisher) diet over a 6 week growing period. At 3 and 6 weeks of age, broilers of each gender on each diet were exposed to 41°C for 1 h in a temperature-controlled chamber while controls were maintained at 24°C. After heat exposure, liver and ileum tissues were collected and preserved in RNAlater for determination of gene expression via Real Time PCR. Significant differences in mRNA expression for HSP90A, HSP90AA and HSP90B due to gender were found in the ileum, but no gender-related differences for these HSPs were found in the liver. In all ...

TY - JOUR. T1 - Extracellular Hsp70 Enhances Mesoangioblast Migration via an Autocrine Signaling Pathway. AU - Sconzo, Gabriella. AU - Geraci, Fabiana. AU - Spinello, Walter. AU - Barreca, Maria Magdalena. AU - Cavalieri, Vincenzo. AU - Tinnirello, Rosaria. AU - Turturici, Giuseppina. AU - Tinnirello, Rosaria. AU - Kaur, Punit. AU - Geraci, Fabiana. AU - Asea, Alexzander A. A.. PY - 2017. Y1 - 2017. N2 - Mouse mesoangioblasts are vessel-associated progenitor stem cells endowed with the ability of multipotent mesoderm differentiation. Therefore, they represent a promising tool in the regeneration of injured tissues. Several studies have demonstrated that homing of mesoangioblasts into blood and injured tissues are mainly controlled by cytokines/chemokines and other inflammatory factors. However, little is known about the molecular mechanisms regulating their ability to traverse the extracellular matrix (ECM). Here, we demonstrate that membrane vesicles released by mesoangioblasts contain Hsp70, ...

TY - JOUR. T1 - IGFBP2 plays an important role in heat shock protein 27-mediated cancer progression and metastasis. AU - Hung, Chin Sheng. AU - Huang, Chien Yu. AU - Lee, Chia Hwa. AU - Chen, Wei Yu. AU - Huang, Ming Te. AU - Wei, Po Li. AU - Chang, Yu Jia. PY - 2017. Y1 - 2017. N2 - Heat shock protein 27 (Hsp27) is a key chaperone that interacts with over 200 client proteins. The expression of Hsp27 might be correlated with poor outcome in many types of cancer. Previous study indicated that Hsp27 might be an important biomarker in hepatocellular carcinoma (HCC). However, the detailed mechanism is less well understood. The shRNA-mediated silencing of Hsp27 decreased the proliferation, migration and invasion of HCC cells. In a xenograft model, the silencing of Hsp27 reduced tumor progression. We revealed that the silencing of Hsp27 led to a reduction in insulinlike growth factor binding protein 2 (IGFBP2), which might mediate proliferation and metastasis through vimentin, snail and beta-catenin. ...

hsp18.5, heat, shock, protein, 18.5, Hsp18.5 | heat shock protein 18.5, Anti-HSP18.5 | clss IV heat shock protein ANTIBODY, O64564.1, AS11 1628

Although heat shock proteins are best characterized in associated with temperature, mounting evidence suggests that heat shock proteins are expressed and play vital roles during many types of cell stress. Heat shock proteins work by helping other proteins fold properly and have been classified in a functional category of proteins called molecular chaperones. Molecular chaperones catalyze the folding of a newly-translated peptide into the secondary and tertiary structures that characterize the mature protein product. Improperly-folded proteins are unstable, prone to aggregation, and dysfunctional. Correct protein folding is extremely important for protein and cell function. . Alterations in protein structure, including secondary and tertiary structure, lead to altered protein function. Similarly, improperly or incompletely folded proteins are likely to be dysfunctional and lead to complications for the cell. It should come as no surprise that improper protein folding in cells of the human body ...

HSP25 is a member of the ubiquitous family of small heat shock proteins belonging to the big class of stress proteins. It is related to acquiring of cellular thermotolerance, can act as molecular chaperone, is able to inhibit polymerization of actin in vitro and can form high molecular weight complexes. In this thesis the isolation, structural and functional characteri-zation of this protein as well as its abundance in different tissues of rats suffering on patho-logical forms of hypertension is analyzed: · A method for rapid isolation of HSP25 out of Ehrlich-ascites-tumor (EAT) was estab-lished. From isolated HSP25 low and high molecular weight material could be obtained. · Analysis of high molecular weight complexes by means of electron microscopy and ana-lytical ultracentrifugation results in a structural model characterized by a cylindrical structure composed of four stacked rings each containing eight HSP25 monomers. · High-molecular weight complexes of recombinant HSP25 are organized as ...

Unfolded proteins in the endoplasmic reticulum (ER) activate the ER transmembrane sensor Ire1 to trigger the unfolded protein response (UPR), a homeostatic signaling pathway that adjusts ER protein folding capacity according to need. Ire1 is a bifunctional enzyme, containing cytoplasmic kinase and RNase domains whose roles in signal transduction downstream of Ire1 are understood in some detail. By contrast, the question of how its ER-luminal domain (LD) senses unfolded proteins has remained an enigma. The 3.0-A crystal structure and consequent structure-guided functional analyses of the conserved core region of the LD (cLD) leads us to a proposal for the mechanism of response. cLD exhibits a unique protein fold and is sufficient to control Ire1 activation by unfolded proteins. Dimerization of cLD monomers across a large interface creates a shared central groove formed by alpha-helices that are situated on a beta-sheet floor. This groove is reminiscent of the peptide binding domains of major ...

Background: In a previous study, we found that heat shock protein 27 (HSP27) was over-expressed in gastric adenocarcinoma (GA) tissue. In this study, our goal was to further verify the expression profile of HSP27 in patients with GA. Methods: Western blot and immunohistochemistry were employed to determine HSP27 expression in 50 paired tumor and adjacent normal tissue. ELISA was used to quantify serum HSP27 concentrations in the same 50 GA patients and 50 healthy individuals. Results: Compared to adjacent normal tissues, HSP27 was over-expressed in 25 (50%, p=0.000) and 24 (48%, p=0.000) cases of GA tissue by Western blot and immunohistochemistry, respectively. ELISA revealed significantly higher serum concentrations of HSP27 in patients with GA patients (mean=986 pg/mL) compared to healthy individuals (mean=573 pg/mL) (p=0.003). In addition, infection with Helicobacter pylori (HP) in healthy individuals was associated with increased expression of HSP27 in both gastric mucosa and serum. ...

The impact of microRNAs (miRNAs) known to regulate numerous biologic processes on complement-dependent cytotoxicity (CDC) was investigated in K562 cells. The C5b-9 complex is the executioner of CDC. Cells protect themselves from CDC by C5b-9 elimination, a process involving the mitochondrial chaperone mortalin/GRP75. Potential miR-200 (b and c) and miR-217 regulatory sites were identified in mortalin mRNA. Overexpression of miR-200b/c or miR-217 lowered the expression of mortalin mRNA. miRNA inhibitors for miR-200b, miR-200c, or miR-217 enhanced mortalin mRNA level. Unexpectedly, these miRNA modulators had no significant effect on mortalin protein level. Metabolic labeling analysis demonstrated that, to compensate for reduction in mortalin mRNA level, the cells increased the rate of synthesis of mortalin protein. Cells overexpressing miR-200b/c or miR-217 showed reduced sensitivity to CDC, whereas inhibition of miR-200c and miR-217 enhanced cell death. miR-200b/c overexpression reduced C5b-9 ...

Pharmacological inhibition of molecular chaperone Hsp90 is an attractive approach for anticancer therapy, since the chaperone activity of Hsp90 is critical for the stability and activity of a variety of cellular client proteins. The list of Hsp90 client proteins is always expanding and includes transcription factors, steroid hormone receptors, protein kinases, oncogenes, proto-oncogenes and signaling molecules.1,2 Since many of these client proteins promote tumor growth, metastasis and angiogenesis, inhibition of Hsp90 can be the one punch that cripples the tumorigenic and metastatic potential of tumors regardless of their tissue or cellular origin. Hsp90 inhibitors have been combined with a variety of chemotherapy and targeted treatment drugs, but the rationale for such combinations is largely empirical. The study by Iwai et al. not only demonstrates potent synergistic antitumor activity upon combining a Wee1 kinase inhibitor and several Hsp90 inhibitors, but the rationale for simultaneous ...

Recently, it has been shown that Akt can be immunoisolated in a complex with hsp90 from cell lysates via a direct interaction between residues 229-309 of Akt and residues 327-340 of the M domain of hsp90.19 In cells, the binding of hsp90 to Akt prevents dephosphorylation of threonine 308 by reducing PP2A-mediated dephosphorylation. To verify the interaction between hsp90 and Akt in our system, we incubated recombinant Akt or endothelial cell lysates with GST-N, -M, and -C domains of hsp90. As seen in Figure 3B, recombinant Akt (left panel) or Akt from cell lysates (right panel) does not significantly interact with GST alone, but interacts with the M domain of hsp90 and binds to a lesser extent to the C domain. The low-level binding to the C domain may represent an additional site of interaction to stabilize Akt to hsp90. The binding of Akt to residues 327-340 and eNOS to residues 442-600 of hsp90β of the M domain suggests that hsp90 can serve as a scaffold for the kinase and it substrate. To ...

Hsp90α is a molecular chaperone protein involved in the structural maturation of oncogenic signaling proteins. Hsp90 was recently identified as an anticancer target; various studies are ongoing to find ways for managing cancer through Hsp90α. However, this approach is limited by reported side-effects. Hypoxia is a hallmark of solid tumors, including those of breast cancer and the extent of tumor hypoxia is associated with resistance to treatment and poor prognosis. One of the major signaling pathways in cancer cells, the Jak2/STAT5b pathway, has been found to be closely correlated with hypoxia. The objective of this study was to investigate the role of Jak2/STAT5b in the regulation of Hsp90α expression so that Hsp90α targeting can be achieved indirectly by modulating the Jak2/STAT5b pathway. We examined the role of the Jak2/STAT5b pathway in the expression of Hsp90α under hypoxic conditions by immunoblotting, reporter gene assays, EMSA and RNA interference analysis. With the help of in vivo ...

Multidrug resistance is a reoccurring obstacle faced in the chemotherapeutic treatments of cancer. Multidrug resistance (MDR) is characterized by high levels of resistance to a number of chemically unrelated drugs. MDR is established in cell lines by expressing high levels of plasma membrane efflux pumps such as P-glycoprotein and MRP-1, both members of the ABC superfamily of transporters. These transporters decrease cellular levels of a particular drug, and through a molecular mechanism not yet identified, also create cellular resistance for other drugs. Interestingly, in a number of cases associated with MDR, cell lines have shown signs of reverse transformation. Reverse transformation is a phenomenon that occurs in transformed cell lines, in which the malignant cells revert back to a normal phenotype and become significantly less tumorigenic ...

Description: The heat-shock proteins (HSPs) belong to a larger group of polypeptides, the stress proteins, that are induced in various combinations in response to environmental challenges and developmental transitions. Synthesis of the small (27-kD) HSP has been shown to be correlated with the acquisition of thermotolerance. The deduced 199-amino acid HSP27 protein shows sequence similarity to mammalian alpha-crystallins. Approximately 20% of its residues are susceptible to phosphorylation. The HSP27 gene, which is mapped to 7q11.23 and has 3 exons1, produced a 2.2-kb transcript in an in vitro transcription assay. Decreasing ROS in cells expressing mutant huntingtin, HSP27 protects cells against oxidative stress2. In other words, HSP27 is a suppressor of polyglutamine (polyQ)-mediated cell death3. Furthermore, MAPKAPK5 is a major stress-activated kinase that can phosphorylate HSP27 in vitro.. Primary Antibody. ...

Heat Shock Protein-27, -60 and -90 expression in gastric cancer: association with clinicopathological variables and patient survival

Acknowledgements. This work was supported by National Science Council, Taiwan, ROC. under Grants NSC84-2311-B-002-007 B01 and NSC85-2311-B-002-010 B13 to C.-Y. L.. Literature Cited. Baumann, G., E. Raschke, M. Bevan, and F. Sch ffl. 1987. Functional analysis of sequence required for transcriptional activation of a soybean heat shock gene in transgenic tobacco plants. EMBO J. 6: 1161-1166.. Chang, P.-F.L., M.L. Narasimhan, P.M. Hasegawa, and R.A. Bressan. 1993. Quantitative mRNA-PCR for expression analysis of low-abundance transcripts. Plant Mol. Biol. Rep. 11: 237-248.. Chou, M., Y.M. Chen, and C.Y. Lin. 1989. Thermotolerance of isolated mitochondria associated with heat shock proteins. Plant Physiol. 89: 617-621.. Czarnecka, E., P.C. Fox, and W.B. Gurley. 1990. In vivo interaction of nuclear proteins with the promoter of soybean heat shock gene Gmhsp 17.5E. Plant Physiol. 94: 935-943.. Czarnecka, E., W.B. Gurley, R.T. Nagao, L.A. Mosquera, and J.L. Key. 1985. DNA sequence and transcript mapping ...