• The team also hopes to launch clinical trials using HSP90 inhibitors against T-ALL. (nyulangone.org)
  • The reported inhibitors of Hsp90 bind to this domain and would inhibit tumor growth and progression. (sinap.ac.cn)
  • A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors. (sinap.ac.cn)
  • Through this deal, BMS gets access to Kosan's two classes of promising anticancer agents, novel Hsp90 (heat shock protein 90) inhibitors and epothilones. (drugdiscoverynews.com)
  • Since the molecular chaperone Hsp90 binds and stabilizes survivin, it is widely believed that down-regulation of survivin is one of the important therapeutic functions of Hsp90 inhibitors such as the phase III clinically trialed compound 17-AAG. (biomedcentral.com)
  • However, Hsp90 interferes with a number of molecules that up-regulate the intracellular level of survivin, raising the question that clinical use of Hsp90 inhibitors may indirectly induce survivin expression and subsequently enhance cancer anti-drug responses. (biomedcentral.com)
  • Here, we demonstrated that Hsp90 inhibitors, geldanamycin and 17-AAG, induced the over-expression of survivin in three different human cancer cell lines as shown by Western blotting. (biomedcentral.com)
  • We showed for the first time that down-regulation of survivin is not a definite therapeutic function of Hsp90 inhibitors. (biomedcentral.com)
  • Instead, targeting Hsp90 with small molecule inhibitors will induce the over-expression of survivin in certain cancer cell lines and subsequently enhances the ability of cell survival in drug-treated situations. (biomedcentral.com)
  • inhibitors that block a protein called heat shock protein 90 (Hsp90). (ki.se)
  • We have developed an innovative method for finding substances that can prevent aging and we identify Hsp90 inhibitors as new and promising candidate substances," says Christian Riedel. (ki.se)
  • Hsp90 inhibitors are already being tested for other treatment purposes, and now further studies are needed to investigate their effect on human ageing. (ki.se)
  • For Hsp90β inhibition, two different chemical inhibitors (Geldanamycin and Novobiocin) were employed, or siRNA transfection procedures were carried out. (biomedcentral.com)
  • The co-chaperone Hep1 is required to prevent the aggregation of mitochondrial Hsp70 proteins. (cipsm.de)
  • Pertinent to AD pathophysiology, heat shock protein 90 (HSP90)/co-chaperone complex folds tau or hyperphosphorylated tau, whereas heat shock protein 70-carboxyl-terminus of HSP70 Interacting protein (HSP70-CHIP) complex mediates degradation 13 , 14 . (nature.com)
  • Im Falle von HSPs zeigte sich strahlungsabhängig die Zunahme der Menge für das HSP60 und HSP90β Protein, während die Menge vom Hyou1 (Mitglied der HSP70 Proteinfamilie) unbeeinflusst blieb. (tu-darmstadt.de)
  • Regulation of signaling protein function and trafficking by the hsp90/hsp70-based chaperone machinery. (sinap.ac.cn)
  • however, almost all the WT tobaccos died after treated at 50 °C and no WT tobacco survived after heat shock at 52 °C. This study firstly showed the function of a hsp70 gene from H. marmoreus . (springeropen.com)
  • Of all HSPs, Hsp70 appears to correlate best with heat resistance either permanent or transient (Li and Mak 2009 ). (springeropen.com)
  • These studies proved that Hsp70 is essential for organisms to survive a severe heat shock. (springeropen.com)
  • Hsp60, Hsp70 and Hsp90 expressions measured by Western blot analysis were not affected after 24 and 48 hours exposure. (edu.pl)
  • Unlike most other chaperone proteins, which aid intracellular proteins, CLU is a Golgi chaperone that facilitates the folding of secreted proteins in an ATP-independent way. (wikipedia.org)
  • It is one of the most abundant cytoplasmic proteins in unstressed cells, where it performs housekeeping functions, controlling the activity, intracellular disposition and proteolytic turnover of a variety of proteins. (biomedcentral.com)
  • These result in imbalances in the connectivity of neuronal circuitry, and also negatively impact the intracellular connectivity of neuronal proteins and protein pathways, contributing to cognitive decline associated with AD 6 . (nature.com)
  • We have examined in this study whether or not increased expression of clusterin is able to protect neuronal cells against intracellular protein aggregation and cytotoxicity, characteristics that are strongly implicated in a range of neurodegenerative diseases. (biomedcentral.com)
  • Following this reasoning, we performed a differential proteomic analysis in order to search for OA-related changes in human articular chondrocyte intracellular proteins, which aimed to unravel those molecular mechanisms that participate in OA pathogenesis [ 4 ]. (biomedcentral.com)
  • G-protein coupled receptors (GPCRs) are membrane proteins that transmit the effects of extracellular ligands to effect changes in the intracellular G-protein signaling system. (gauss-centre.eu)
  • In particular, custirsen, an antisense oligonucleotide that blocks the CLU mRNA transcript, enhanced heat-shock protein 90 (HSP90) inhibitor activity by suppressing the heat-shock response in castrate-resistant prostate cancer, and is currently in phase III trials. (wikipedia.org)
  • Moreover we examine the role of a monoclonal antibody (mAb) against HSP90, mAb 4C5, regarding these interactions and its value as a potential inhibitor of human breast cancer cell invasion and metastasis. (biomedcentral.com)
  • Here, we synthesized FS23, a small molecule inhibitor of hsp90 and collected X-ray diffraction data of the complex crystal of Hsp90-FS23. (sinap.ac.cn)
  • The deal with BMS will provide the resources to pursue further development of its Hsp90 inhibitor KOS-953 currently in Phase II clinical trials for both multiple myeloma (in combination with Velcade) and in HER2+ metastatic breast cancer and for its epothilone candidate for the treatment of solid tumors KOS-1584 which just recently entered Phase II trials. (drugdiscoverynews.com)
  • Unlike other IAPs, survivin is a bifunctional protein that functions as a key regulator of mitosis and inhibitor of programmed cell death. (biomedcentral.com)
  • Nevertheless, 60% of the 10 trial participants randomly assigned to the experimental HSP90 inhibitor RGRN-305 (250 mg/day) for 16 weeks achieved an HiSCR50 response, compared with 20% of the five participants given placebo. (medthority.com)
  • A small-molecule screen reveals that HSP90? (musc.edu)
  • Inhibition of HSP90β expression improved neurological deficits and alleviated brain injury by increasing EAAT2 expression. (spandidos-publications.com)
  • These results suggested that HSP90β is involved in the process of cerebral ischemia‑reperfusion injury in rats and that inhibition of HSP90β expression increases EAAT2 levels, conferring a neuroprotective effect in MCAO model rats. (spandidos-publications.com)
  • The current study suggests that dual inhibition of Hsp90 and survivin may be warranted. (biomedcentral.com)
  • Inhibition of Hsp90β by the chemicals Geldanamycin (GA) and Novobiocin (NB) caused a dose-dependent decrease of the NO production induced by IL-1β in chondrocytes, up to basal levels. (biomedcentral.com)
  • The nuclear isoform encodes a 49 kDa protein, while the secretory isoform, which is the main gene transcript, encodes a 75-80 kDa protein after maturation (glycosylation, secretion, and dimerization). (wikipedia.org)
  • As a molecular chaperone, HSP90 regulates the conformational maturation and functional stability of many signaling proteins in cells, serves important roles in cell growth, differentiation, apoptosis and tumor development and is an important antitumor target ( 8 , 9 ). (spandidos-publications.com)
  • The ATP-dependent molecular chaperone Hsp90 (heat-shock protein 90) is essential for the maturation of hormone receptors and protein kinases. (embl.de)
  • In vivo studies in yeast and in mammalian cells revealed that Aha1 is not specific for kinase activation, but also contributes to maturation of hormone receptors, proposing a general role for this cofactor in the activation of Hsp90-dependent client proteins. (embl.de)
  • This family plays essential roles in the folding, maturation and activity of many proteins that are involved in signal transduction and transcriptional regulation. (biomedcentral.com)
  • Additionally, we have reported results showing that a monoclonal antibody (mAb) recognizing both the α and the β isoforms of HSP90, mAb 4C5, inhibits melanoma cell invasion and metastasis by binding selectively to the surface pool of HSP90 [ 13 ]. (biomedcentral.com)
  • Mechanistic studies further reveal that the binding of NAP1 to the cellular chaperone heat shock protein 90 (HSP90) is required for its protein stabilization, and NAP1 plays an essential role in HSP90-mediated invasion and metastasis by provoking MMP9 activation and the epithelial-to-mesenchymal transition in NSCLC cells. (biomedcentral.com)
  • MAb 4C5, while not affecting the secretion of inactive MMPs, inhibits their activation by disrupting their interaction extracellularly with both isoforms of HSP90. (biomedcentral.com)
  • The in vivo studies revealed that mAb 4C5 significantly inhibits the metastatic deposit formation of MDAMB453 cells into the lungs of SCID mice. (biomedcentral.com)
  • A substance that inhibits that activity of the Hsp90 heat shock protein. (hsp90-inhibitors.com)
  • The mitochondria have their own chaperones and proteolytic enzymes that remove damaged or unfolded proteins [ 18 - 20 ]. (hindawi.com)
  • During the process of client protein activation, Hsp90 co-operates with cofactors/co-chaperones of unique sequence, e.g. (embl.de)
  • HSP90) and induction of chaperones promoting tau degradation (e.g. (nature.com)
  • The ability of neurons to manage the burden of misfolded proteins and to resist their accumulation into insoluble protein deposits depends critically on the functioning of molecular chaperones. (biomedcentral.com)
  • There are a large number of co-chaperones that are known to bind to Hsp90 and regulate its ATP hydrolysis and chaperoning activity. (biophysics.org)
  • Our results suggest a model where the E3 ubiquitin ligase CHIP cooperates with other ubiquitination factors to remodel native AhR-hsp90 complexes and where co-chaperones such as the XAP2 may affect the ability of CHIP to target AhR complexes for ubiquitination. (psu.edu)
  • Hsp90β is a member of the Hsp90 family of protein chaperones. (biomedcentral.com)
  • 2007 ). Heat shock proteins (HSPs) are a group of conserved proteins that function as molecular chaperones and accumulate under heat shock. (springeropen.com)
  • The gene is highly conserved in species, and the protein is widely distributed in many tissues and organs, where it participates in a number of biological processes, including lipid transport, membrane recycling, cell adhesion, programmed cell death, and complement-mediated cell lysis. (wikipedia.org)
  • Further laboratory experiments in T-ALL mice and human cells showed that silencing the gene behind production of HSP90 efficiently killed leukemia cells, especially those with the highest NOTCH1 and HSP90 activity. (nyulangone.org)
  • Transcriptomes from the tissues of the brain-pituitary-gonad (BPG) axis of T10 samples revealed a differential gene expression profile compared to the other experimental groups, with clustering in a principal component analysis and in heat maps of all differentially expressed genes. (biomedcentral.com)
  • Furthermore, a functional analysis of differentially expressed genes revealed enriched gene ontology terms involved in the regulation of circadian rhythm, histone modification, meiotic nuclear division, and others. (biomedcentral.com)
  • Among these, 17.5% had putative functions in signaling, 14.3% were assigned to cell cycle and gene expression, 8.7% were linked to the cytoskeleton or inner membrane complex, 7.9% were involved in proteostasis and 6.4% in metabolism, 12.7% were cell surface-associated proteins, 11.9% were assigned to other functions, and 20.6% represented genes of unknown function. (biomedcentral.com)
  • Interestingly, real-time PCR and translation inhibition studies revealed that survivin was over-expressed partially through the up-regulation of protein translation instead of gene transcription in A549 cancer cells. (biomedcentral.com)
  • In contrast, the thermally sensitive population exhibited higher basal levels of heat shock proteins and had three times fewer changes in gene expression overall. (frontiersin.org)
  • This gene product is a bZIP protein, which was also identified as a cellular transcription factor that binds to an enhancer in the promoter of the T cell leukemia virus type 1 promoter. (cancerindex.org)
  • It has been found that upon accumulation of unfolded proteins in the endoplasmic reticulum (ER), the mRNA of this gene is processed to an active form by an unconventional splicing mechanism that is mediated by the endonuclease inositol-requiring enzyme 1 (IRE1). (cancerindex.org)
  • What does this gene/protein do? (cancerindex.org)
  • qPCR analysis revealed that the transcription level of hmhsp70 in H. marmoreus mycelia increased after heat shock treatment in high temperature (42 °C) compared with untreated mycelia (at 25 °C). Transgenic tobaccos expressing hmhsp70 gene showed enhanced resistance to lethal temperature compared with the wild type (WT) plants. (springeropen.com)
  • By contrast, Hsp90 inhibition does not increase the rate of gene-inactivating point mutations. (bcm.edu)
  • CLU promotes cell survival by a number of means, including inhibition of BAX on the mitochondrial membrane, activation of the phosphatidylinositol 3-kinase/protein kinase B pathway, modulation of extracellular signal-regulated kinase (ERK) 1/2 signaling and matrix metallopeptidase-9 expression, promotion of angiogenesis, and mediation of the nuclear factor kappa B (NF-κB) pathway. (wikipedia.org)
  • Increasing data reveal an extracellular chaperoning activity for HSP90. (biomedcentral.com)
  • Finally, we have presented data indicating that surface HSP90 interacts specifically with the extracellular domain of HER-2 and that this interaction which is necessary for the receptor's activation leading to breast cancer cell invasion, is disrupted by mAb 4C5 [ 14 ]. (biomedcentral.com)
  • Extracellular CLU-client protein complexes are susceptible to endocytic clearance by monocytes and hepatocytes, and this action is thought to form a central plank in the operation of a co-ordinated system to maintain extracellular protein homeostasis (proteostasis) [ 14 ]. (biomedcentral.com)
  • Hsp90 as a new therapeutic target for cancer therapy: the story unfolds. (sinap.ac.cn)
  • Clusterin (apolipoprotein J) is a 75-80 kDa disulfide-linked heterodimeric protein associated with the clearance of cellular debris and apoptosis. (wikipedia.org)
  • The present results show how Hsp90β modulates NO production and NO-mediated cellular death in human OA chondrocytes. (biomedcentral.com)
  • Hsp90 modulates CAG repeat instability in human cells. (bcm.edu)
  • Therefore we analysed whether complexes of Aha1, p23, p50, Hop and a cyclophilin with Hsp90 are disrupted by the other four cofactors by gel permeation chromatography using purified proteins. (embl.de)
  • Upon phosphorylation, R-SMADs recruit the co-SMAD SMAD-4 to form protein complexes that translocate into the nucleus and exhibit transcriptional activity. (springer.com)
  • The analysis of the sucrose-gradient-fractionated in vitro translated AhR complexes revealed that CHIP can mediate hsp90 ubiquitination while cooperating with unidentified factors to promote the ubiquitination of mature unliganded AhR complexes. (psu.edu)
  • The trimeric Sec61/SecY complex is a protein-conducting channel (PCC) for secretory and membrane proteins. (cipsm.de)
  • Whilst CLU is predominantly a secreted protein, multiple independent studies have now clearly established that during conditions of ER stress, CLU secretion is inhibited, and full-length CLU exits the secretory system to enter the cytosol. (biomedcentral.com)
  • Cells express a pool of thousands of different proteins that need to be tightly controlled for proper cellular structure, organization, and function. (hindawi.com)
  • The regulation of the aryl hydrocarbon receptor (AhR) protein levels has been an area of keen interest, given its important role in mediating the cellular adaptation and toxic response to several environmental pollutants. (psu.edu)
  • In this study, we established that CHIP could associate with the AhR at cellular levels of these two proteins, suggesting a potential role for CHIP in the regulation of the AhR complex. (psu.edu)
  • The anti-inflammatory actions of corticosteroids occur with a considerable delay (within hours or days) because of the multiple steps of cellular actions required to change protein expression. (ersjournals.com)
  • 2018 ). Hsp70s as molecular chaperone are involved in a wide variety of cellular processes, including protein biogenesis, protection of the proteome from stress, recovery of proteins from aggregates and facilitation of protein translocation across membranes (Clerico et al. (springeropen.com)
  • Ageing leads to a gradual dysfunction of the proteostasis network and thus to proteome instability due to accumulation of damaged and/or misfolded proteins [ 2 ]. (hindawi.com)
  • Aha1 competes with Hop, p50 and p23 for binding to the molecular chaperone Hsp90 and contributes to kinase and hormone receptor activation. (embl.de)
  • Development of a purine-scaffold novel class of Hsp90 binders that inhibit the proliferation of cancer cells and induce the degradation of Her2 tyrosine kinase. (sinap.ac.cn)
  • We report that impairment of Hsp90 in human cells induces contractions of CAG repeat tracks by tenfold. (bcm.edu)
  • Inhibition of the recombinase Rad51, a downstream target of Hsp90, induces a comparable increase in repeat instability, suggesting that Hsp90-enabled homologous recombination normally functions to stabilize CAG repeat tracts. (bcm.edu)
  • Heat shock proteins (HSPs) are highly conserved and immunogenic proteins that are shared among diverse groups of mammals and microbial agents. (eg.net)
  • HSPs are detected in all organisms when cells were exposed to various stresses such as heat, cold, heavy metal, or certain nutrients. (springeropen.com)
  • The final HS medication trial in the late-breaking sessions was a pilot randomised, double-blind trial demonstrating the feasibility of targeting heat shock proteins (HSPs) to improve HS symptoms. (medthority.com)
  • Our insights demonstrate the importance and functional regulation of the HSP90-NAP1 protein complex in cancer metastatic signaling, which spur new avenues to target this interaction as a novel approach to block NSCLC metastasis. (biomedcentral.com)
  • Here we demonstrate that PSRP1 is not a bona fide ribosomal protein, but rather a functional homologue of the Escherichia coli cold-shock protein pY. (cipsm.de)
  • This is known to lead to the expression of so-called chaperone proteins that improve the animals' ability to keep their proteins correctly folded and thus in a functional state throughout their lifetime. (ki.se)
  • Crystal structure of an Hsp90-geldanamycin complex: targeting of a protein chaperone by an antitumor agent. (sinap.ac.cn)
  • The discovery that the NOTCH1 pathway takes control of heat shock transcription factor 1 (HSF1) signaling in T-cell acute lymphoblastic leukemia , or T-ALL, suggests that blocking one or more genes in the HSF1 pathway could represent a new approach in treating the aggressive disease, researchers say. (nyulangone.org)
  • Dr. Aifantis says his team next plans to evaluate the effects of another eight proteins produced by genes active in the HSF1 pathway to see if any show promising anticancer activity in T-ALL. (nyulangone.org)
  • This thermoception may have caused the observed effects through epigenetic mechanisms, since all analysed tissues further revealed differentially expressed genes involved in histone modification. (biomedcentral.com)
  • For 40% of the identified genes there has as yet not been any protein evidence. (biomedcentral.com)
  • For selected genes, a regulated expression during gametogenesis was confirmed on the protein level, using quantitative confocal microscopy. (biomedcentral.com)
  • The continuous increase in poultry production over the last decades to meet the high growing demand and provide food security has attracted much concern due to the recent negative impacts of the most challenging environmental stressor, heat stress (HS), on birds. (frontiersin.org)
  • Heat stress (HS) is widely classified into acute heat stress (AHS), which is the intense environmental temperature for a brief period and chronic heat stress (CHS) characterized by high temperature for a longer duration. (frontiersin.org)
  • Here, we demonstrate that the endoplasmic reticulum stress sensor inositol-requiring enzyme 1 (IRE1α) and its substrate transcription factor X-box-binding protein 1 (XBP1) drive NK cell responses against viral infection and tumors in vivo. (cancerindex.org)
  • The 70-kD heat shock proteins (Hsp70s) have been proved to be important for stress tolerance and protein folding and unfolding in almost all organisms. (springeropen.com)
  • In a study published in Science magazine, Dr. Nicolas Rohner and colleagues showed that stress can affect the ability for HSP90 to do its job thereby unmasking these alternative versions of proteins which may lead to adaptation in some cases. (scienceblogs.com)
  • The Hsp90 molecular chaperone has been implicated as a contributor to evolution in several organisms by revealing cryptic variation that can yield dramatic phenotypes when the chaperone is diverted from its normal functions by environmental stress. (bcm.edu)
  • The crystal structure of the carboxy-terminal dimerization domain of htpG, the Escherichia coli Hsp90, reveals a potential substrate binding site. (sinap.ac.cn)
  • Our study shows how the NOTCH1 pathway hijacks the heat shock transcription factor 1 pathway to promote tumor growth," says study senior investigator Iannis Aifantis, PhD , professor and chair of the Department of Pathology at NYU Langone's Perlmutter Cancer Center . (nyulangone.org)
  • The proteostasis network (PN) is an assembly of distinct dynamic molecular pathways that control the functionality of the proteome (proteome homeodynamics) during protein synthesis, folding, trafficking, and degradation. (hindawi.com)
  • During protein synthesis, ribosomes become stalled on polyproline-containing sequences, unless they are rescued in archaea and eukaryotes by the initiation factor 5A (a/eIF-5A) and in bacteria by the homologous protein EF-P. While a structure of EF-P bound to the 70S ribosome exists, structural insight into eIF-5A on the 80S ribosome has been lacking. (cipsm.de)
  • 5 Since changes in de novo protein synthesis are the basis for glucocorticoid effectiveness, the lack of a modulatory effect on platelet functions is not surprising given that these cells have been regarded as incapable of synthetic activity. (ashpublications.org)
  • HS causes poor meat quality by impairing protein synthesis and augmenting undesirable fat in meat. (frontiersin.org)
  • Aha1 (activator of Hsp90 ATPase 1), p23 or p50, and with cofactors containing TPR (tetratricopeptide repeat) domains, e.g. (embl.de)
  • We laid particular focus on those researches that reveal how exosomes regulate the tumor immune microenvironment (TIME) and how exosomal cargos affect the progression of HCC. (hindawi.com)
  • Studies revealed that inhibition of CLU resulted in increased effectiveness of chemotherapeutic agents to kill tumor cells. (wikipedia.org)
  • Heat shock protein (HSP) 90 is abundant in cells, mainly in the form of homodimers, including HSP90α and HSP90β. (spandidos-publications.com)
  • Our results showed that both HSP90α and HSP90β are secreted by MDAMB453 human breast cancer cells and interact with MMP2 and MMP9. (biomedcentral.com)
  • Both isoforms of HSP90 are secreted by MDAMB453 cells and interact with MMP2 and MMP9. (biomedcentral.com)
  • The heat shock protein 90 (HSP90) is a molecular chaperone which exists in mammalian cells in two isoforms that share 86% aminoacid conservation (HSP90α and HSP90β). (biomedcentral.com)
  • Nck-associated protein 1 (NAP1/NCKAP1), a protein that associates with the Src homology 3 (SH3) domain of NCK protein both in vitro and in intact cells, was found to localize along the lamellipodia and to mediate contact-dependent cell migration [ 4 ]. (biomedcentral.com)
  • Our previous studies further demonstrated that NAP1 is required for the protein stability of WASF3 in breast cancer cells, implicating that NAP1 is a critical regulator in favor of breast cancer metastasis [ 5 ]. (biomedcentral.com)
  • And because early experiments with the drug in animals and human cells show that blocking HSP90 kills only cancer cells, Dr. Aifantis says its use is likely to have fewer side effects than current T-ALL treatments, such as chemotherapy, which kills both normal and cancer cells. (nyulangone.org)
  • He loved microscopes and watching the proteins and molecules that make up cells move around. (biophysics.org)
  • Surprisingly, CHIP silencing in Hepa-1c1c7 cells by siRNA methods did not reveal the function of CHIP in the AhR complex, because it did not affect well-characterized activities of the AhR nor affect its steady-state protein levels. (psu.edu)
  • In addition, 17-AAG-treated A549, HONE-1 and HT-29 cells showed reduced proteasomal activity while inhibition of 26S proteasome activity further increased the amount of survivin protein in cells. (biomedcentral.com)
  • Heat shock protein 90 (Hsp90) is a molecular chaperone that assists the correct folding and stabilization of various proteins in cells. (biomedcentral.com)
  • The role of this protein in chondrocytes is not well understood, although its increase in osteoarthritic cells has been reported. (biomedcentral.com)
  • Indirect immunofluorescence assays were performed to evaluate the presence of Hsp90β in stimulated cells. (biomedcentral.com)
  • Among the proteins that were significantly altered in OA chondrocytes, we identified the β subunit of the chaperone Hsp90 as increased in diseased cells. (biomedcentral.com)
  • Fluorescence microscopy studies of the actin protein revealed no changes of the immunolabelling profile in the renal cells cultured in the presence of Eu:HAp nanoparticles. (edu.pl)
  • In addition, as a cancer drug target, Hsp90 inhibition has been documented to sensitize cells to DNA-damaging agents, suggesting a function for Hsp90 in DNA repair. (bcm.edu)
  • Consideration of related TPx crystal structures indicates that the missing cross peaks correspond to a region of the protein that must display conformational plasticity necessary for the mechanism of action suggesting that the spectrum is affected by conformational exchange processes. (ndltd.org)
  • Here we investigate the interaction of the secreted isoforms of HSP90 with matrix metalloproteinases (MMP) MMP2 and MMP9. (biomedcentral.com)
  • MAb 4C5 prevents MMP2 and MMP9 activation, by disrupting their interaction with HSP90. (biomedcentral.com)
  • This is accomplished by increasing both the interaction strength and number of interactions among participant proteins, which is not necessarily accompanied by a change in expression levels. (nature.com)
  • High resolution X-ray crystallography shows that FS23 interacted with Hsp90,N, at the nucleotide binding cleft, and this suggests that FS23 may complete with nucleotides to bind to Hsp90,N,. The crystal structure and the interaction between Hsp90,N, and FS23 suggest a rational basis for the design of novel antitumor drugs. (sinap.ac.cn)
  • CLU is a molecular chaperone responsible for aiding protein folding of secreted proteins, and its three isoforms have been differentially implicated in pro- or antiapoptotic processes. (wikipedia.org)
  • HtpG, the prokaryotic homologue of Hsp90, stabilizes a phycobilisome protein in the cyanobacterium Synechococcus elongatus PCC 7942. (sinap.ac.cn)
  • Moreover, the NYU School of Medicine scientists who led the latest research efforts say that because an experimental anticancer drug is already in development against one of these targets, heat shock protein 90 (HSP90), the new study identifies the subset of T-ALL patients most likely to benefit from the new therapy. (nyulangone.org)
  • Proteomics analysis of plasma from middle-aged adults identifies protein markers of dementia risk in later life. (bcm.edu)
  • We used the amyotrophic lateral sclerosis-associated protein TDP-43 as a primary model to investigate the effects of clusterin on protein aggregation and neurotoxicity in complementary in vitro, neuronal cell and Drosophila systems. (biomedcentral.com)
  • In addition, the immunophilin-like protein XAP2 was able to partially protect the AhR from CHIP-mediated ubiquitination in vitro. (psu.edu)
  • Finally, the in vitro biological effects of Eu:HAp nanoparticles were evaluated by focusing on the F-actin filament pattern and heat shock proteins (Hsp) expression in HEK293 human kidney cell line. (edu.pl)
  • The heterochromatin-enriched HP1 proteins play a critical role in regulation of transcription. (cipsm.de)
  • Plastid-specific ribosomal proteins (PSRPs) have been proposed to play roles in the light-dependent regulation of chloroplast translation. (cipsm.de)
  • HSP90 inhibition may also enhance synaptic protein expression via activation of heat shock factor 1 (HSF-1) transcriptional regulation 16 . (nature.com)
  • Heat-shock protein 90, a chaperone for folding and regulation. (sinap.ac.cn)
  • The carboxyl terminus of hsc70-interacting protein (CHIP) ubiquitin ligase was previously associated with the regulation of the aryl hydrocarbon receptor, although the mechanisms were not directly demonstrated. (psu.edu)
  • Immunofluorescence was used to detect HSP90β expression localization and the expression levels of HSP90β and EAAT2 were determined using western blotting and reverse transcription‑quantitative PCR. (spandidos-publications.com)
  • The researchers show that the substances work by activating a protein called heat shock transcription factor 1 (Hsf-1). (ki.se)
  • Hypoxia maintains HIFα protein expression through inhibition of prolyl hydroxylases and IL-1 is suggested to effect subunit expression at the level of transcription and in a similarly post-translational fashion [ 26 ]. (biomedcentral.com)
  • More recently we determined that REMFS decreases toxic protein beta amyloid levels, which is the cause of Alzheimer's disease (AD), in human neuronal cultures. (intechopen.com)
  • A series of studies have revealed that exosomes-mediated intercellular transfer of proteins, nucleic acids, and metabolites plays a crucial role in the initiation and progression of HCC, hypoxia and angiogenesis, chemotherapy sensitivity, and cell death mode and regulates the immune microenvironment. (hindawi.com)
  • Ligand-binding studies revealed the presence of a high- and low-affinity binding site for [ 3 H]-dexamethasone in platelets. (ashpublications.org)
  • Studies previously conducted show that HS negatively affects the skeletal muscle growth and development by changing its effects on myogenic regulatory factors, insulin growth factor-1, and heat-shock proteins. (frontiersin.org)
  • Most studies revealed a proportional correlation between thyroid gland dysfunction and the exposure duration, intensity, and SAR value of radiation. (saferemr.com)
  • Here we explore the potential role of Hsp90 in modulating the stability of nucleotide repeats, which in a number of species, including humans, exert subtle and quantitative consequences for protein function, morphological and behavioral traits, and disease. (bcm.edu)
  • Immunofluorescence analyses demonstrate that the NO donors NOC-12 and SNP also increased Hsp90β. (biomedcentral.com)
  • These structures provide the backbone upon which proteome-wide connectivity, and in turn, protein networks become disturbed and ultimately dysfunctional. (nature.com)
  • The present study aimed to investigate the effects of changes in heat shock protein (HSP)90β expression and verify whether HSP90β regulates EAAT2 expression in a cerebral ischemia‑reperfusion injury model. (spandidos-publications.com)
  • Lentivirus construction and injection were used to interfere with the expression of HSP90β. (spandidos-publications.com)
  • HSP90β expression coincided with astrocyte markers in the ischemic penumbra area, while no expression was observed in microglia. (spandidos-publications.com)
  • Epithelial membrane protein 2 (EMP2) expression is reduced upon cell cycle arrest and is sufficient to enhance ferroptosis in response to direct GPX4 inhibition. (bvsalud.org)
  • Nck-associated protein 1 (NAP1/NCKAP1) is highly expressed in primary non-small-cell lung cancer (NSCLC) when compared with adjacent normal lung tissues, and its expression levels are strongly associated with the histologic tumor grade, metastasis and poor survival rate of NSCLC patients. (biomedcentral.com)
  • The purpose of this study is to determine whether targeting Hsp90 can alter survivin expression differently in different cancer cell lines and to explore possible mechanisms that cause the alteration in survivin expression. (biomedcentral.com)
  • It may increase expression of viral proteins by acting as the DNA binding partner of a viral transactivator. (cancerindex.org)
  • Scope includes mutations and abnormal protein expression. (cancerindex.org)
  • The capacity of Hsp90 to modulate repeat-tract lengths suggests that the chaperone, in addition to exposing cryptic variation, might facilitate the expression of new phenotypes through induction of novel genetic variation. (bcm.edu)
  • Relatively little is known about regulatory mechanisms in HIF signalling, especially with regards to HIF-2 but other putative mechanisms for the maintenance of HIF expression include stabilisation through binding of the molecular chaperone heat shock protein, HSP90 [ 28 ]. (biomedcentral.com)
  • TGF-β1 binding to either subunit initiates their assembly into a heteromeric protein complex that consists of two type I and two type II subunits. (springer.com)
  • Preexisting antivector immunity can severely compromise the ability of Salmonella enterica serovar Typhimurium live vaccines to induce protective CD8 T-cell frequencies after type III secretion system-mediated heterologous protein translocation in orally immunized mice. (cipsm.de)
  • Membrane phase separation into liquid-ordered and liquid-disordered domains has been speculated to play a role in controlling the cleavage of amyloid precursor protein (APP) by the α-secretase ADAM10 (a disintegrin and metalloproteinase domain-containing protein 10) and the β-secretase BACE1 (𝛽-site amyloid precursor protein cleaving enzyme 1), affecting the formation of the amyloid-β peptides, oligomers, and fibrils implicated in Alzheimer's disease. (biophysics.org)
  • The present study aimed to explore the role of Hsp90β in key aspects of OA pathogenesis. (biomedcentral.com)
  • A drug blocking HSP90 is already in early clinical trials elsewhere, led by study co-investigator Gabriela Chiosis, PhD, as a treatment for breast cancer . (nyulangone.org)
  • The N-terminal domain of heat shock protein 90 (Hsp90,N,) is responsible for the catalytic activity of Hsp90. (sinap.ac.cn)