HSP90

Summary

Gene Symbol: HSP90
Description: heat shock protein 90 alpha family class A member 1
Alias: EL52, HEL-S-65p, HSP86, HSP89A, HSP90A, HSP90N, HSPC1, HSPCA, HSPCAL1, HSPCAL4, HSPN, Hsp103, Hsp89, Hsp90, LAP-2, LAP2, heat shock protein HSP 90-alpha, HSP 86, LPS-associated protein 2, epididymis luminal secretory protein 52, epididymis secretory sperm binding protein Li 65p, heat shock 86 kDa, heat shock 90kD protein 1, alpha, heat shock 90kD protein 1, alpha-like 4, heat shock 90kD protein, alpha-like 4, heat shock 90kDa protein 1, alpha, heat shock protein 90kDa alpha (cytosolic), class A member 1, heat shock protein 90kDa alpha family class A member 1, lipopolysaccharide-associated protein 2, renal carcinoma antigen NY-REN-38
Species: human
Products:     HSP90

Top Publications

  1. Vaughan C, Gohlke U, Sobott F, Good V, Ali M, Prodromou C, et al. Structure of an Hsp90-Cdc37-Cdk4 complex. Mol Cell. 2006;23:697-707 pubmed
    Activation of many protein kinases depends on their interaction with the Hsp90 molecular chaperone system...
  2. Ying W, Du Z, Sun L, Foley K, Proia D, Blackman R, et al. Ganetespib, a unique triazolone-containing Hsp90 inhibitor, exhibits potent antitumor activity and a superior safety profile for cancer therapy. Mol Cancer Ther. 2012;11:475-84 pubmed publisher
    Targeted inhibition of the molecular chaperone Hsp90 results in the simultaneous blockade of multiple oncogenic signaling pathways and has, thus, emerged as an attractive strategy for the development of novel cancer therapeutics...
  3. Zhang L, Nephew K, Gallagher P. Regulation of death-associated protein kinase. Stabilization by HSP90 heterocomplexes. J Biol Chem. 2007;282:11795-804 pubmed
    Death-associated protein kinase (DAPK) has been found associated with HSP90, and inhibition of HSP90 with 17-alkylamino-17-demethoxygeldanamycin reduced expression of DAPK...
  4. Gibbs A, Schwartzman J, Deng V, Alumkal J. Sulforaphane destabilizes the androgen receptor in prostate cancer cells by inactivating histone deacetylase 6. Proc Natl Acad Sci U S A. 2009;106:16663-8 pubmed publisher
    ..histone deacetylase 6 (HDAC6), influences the acetylation state of a key androgen receptor (AR) chaperone, HSP90. AR is the central signaling pathway in prostate cancer, and its inhibition is used for both prevention and ..
  5. Liu X, Yan Z, Huang L, Guo M, Zhang Z, Guo C. Cell surface heat shock protein 90 modulates prostate cancer cell adhesion and invasion through the integrin-?1/focal adhesion kinase/c-Src signaling pathway. Oncol Rep. 2011;25:1343-51 pubmed publisher
    ..b>Hsp90 has also been detected on the plasma membrane of cells, and its expression has been suggested to correlate with ..
  6. da Silva Correia J, Miranda Y, Leonard N, Ulevitch R. SGT1 is essential for Nod1 activation. Proc Natl Acad Sci U S A. 2007;104:6764-9 pubmed
    ..studies have shown that the R protein function is determined by multiple proteins including SGT1, Rar1, and HSP90. Here we show that SGT1 positively regulates Nod1 activation...
  7. Moriwaki Y, Kim Y, Ido Y, Misawa H, Kawashima K, Endo S, et al. L347P PINK1 mutant that fails to bind to Hsp90/Cdc37 chaperones is rapidly degraded in a proteasome-dependent manner. Neurosci Res. 2008;61:43-8 pubmed publisher
    ..Here we report that PINK1 forms a complex with the molecular chaperones Hsp90 and Cdc37/p50 within cells, which appears to enhance its stability...
  8. Johnson N, Johnson S, Yao W, Li Y, Choi Y, Bernhardy A, et al. Stabilization of mutant BRCA1 protein confers PARP inhibitor and platinum resistance. Proc Natl Acad Sci U S A. 2013;110:17041-6 pubmed publisher
    ..Here, we show HSP90-mediated stabilization of a BRCT domain mutant BRCA1 protein under PARP inhibitor selection pressure...
  9. Maloney A, Clarke P, Naaby Hansen S, Stein R, Koopman J, Akpan A, et al. Gene and protein expression profiling of human ovarian cancer cells treated with the heat shock protein 90 inhibitor 17-allylamino-17-demethoxygeldanamycin. Cancer Res. 2007;67:3239-53 pubmed
    ..17AAG) results from inhibition of the molecular chaperone heat shock protein 90 (HSP90) and subsequent degradation of multiple oncogenic client proteins...

More Information

Publications77

  1. Zagouri F, Sergentanis T, Nonni A, Papadimitriou C, Michalopoulos N, Domeyer P, et al. Hsp90 in the continuum of breast ductal carcinogenesis: Evaluation in precursors, preinvasive and ductal carcinoma lesions. BMC Cancer. 2010;10:353 pubmed publisher
    b>Hsp90 (heat shock protein90) is a chaperone protein essential for preserving and regulating the function of various cellular proteins...
  2. Ehrlich E, Wang T, Luo K, Xiao Z, Niewiadomska A, Martinez T, et al. Regulation of Hsp90 client proteins by a Cullin5-RING E3 ubiquitin ligase. Proc Natl Acad Sci U S A. 2009;106:20330-5 pubmed publisher
    We report a link between Cullin5 (Cul5) E3 ubiquitin ligase and the heat shock protein 90 (Hsp90) chaperone complex. Hsp90 participates in the folding of its client proteins into their functional conformation...
  3. Chandarlapaty S, Scaltriti M, Angelini P, Ye Q, Guzman M, Hudis C, et al. Inhibitors of HSP90 block p95-HER2 signaling in Trastuzumab-resistant tumors and suppress their growth. Oncogene. 2010;29:325-34 pubmed publisher
    ..We find that both full-length and p95-HER2 interact with the HSP90 chaperone protein and are degraded in tumor cells exposed to HSP90 inhibitors in tissue culture and in vivo...
  4. Kumar P, Ambasta R, Veereshwarayya V, Rosen K, Kosik K, Band H, et al. CHIP and HSPs interact with beta-APP in a proteasome-dependent manner and influence Abeta metabolism. Hum Mol Genet. 2007;16:848-64 pubmed
    ..CHIP also hastens the clearance of Abeta in a manner consistent with its known neuroprotective properties. ..
  5. Weng S, Tseng S, Huang Y, Chen H, Lin Y. Inhibition of thymidine phosphorylase expression by using an HSP90 inhibitor potentiates the cytotoxic effect of cisplatin in non-small-cell lung cancer cells. Biochem Pharmacol. 2012;84:126-36 pubmed publisher
    ..In this study, we examined the role of TP expression in relation to the HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG)-induced cytotoxicity in two non-small-cell lung cancer (..
  6. Boulon S, Pradet Balade B, Verheggen C, Molle D, Boireau S, Georgieva M, et al. HSP90 and its R2TP/Prefoldin-like cochaperone are involved in the cytoplasmic assembly of RNA polymerase II. Mol Cell. 2010;39:912-924 pubmed publisher
    ..These included a cytoplasmic complex containing subunits Rpb1 and Rpb8 associated with the HSP90 cochaperone hSpagh (RPAP3) and the R2TP/Prefoldin-like complex...
  7. Lotz G, Brychzy A, Heinz S, Obermann W. A novel HSP90 chaperone complex regulates intracellular vesicle transport. J Cell Sci. 2008;121:717-23 pubmed publisher
    Heat shock protein 90 (HSP90) is considered a specialized molecular chaperone that controls the folding of cell-regulatory proteins such as steroid receptors and kinases...
  8. Sun F, Mi Z, Condliffe S, Bertrand C, Gong X, Lu X, et al. Chaperone displacement from mutant cystic fibrosis transmembrane conductance regulator restores its function in human airway epithelia. FASEB J. 2008;22:3255-63 pubmed publisher
    ..Hsp70 and Hsp90 associated equally with WT and DeltaF508 CFTR, whereas nearly twice as much of the Hsp90 cochaperone, Aha1, ..
  9. Richter K, Soroka J, Skalniak L, Leskovar A, Hessling M, Reinstein J, et al. Conserved conformational changes in the ATPase cycle of human Hsp90. J Biol Chem. 2008;283:17757-65 pubmed publisher
    The dimeric molecular chaperone Hsp90 is required for the activation and stabilization of hundreds of substrate proteins, many of which participate in signal transduction pathways...
  10. Koulov A, LaPointe P, Lu B, Razvi A, Coppinger J, Dong M, et al. Biological and structural basis for Aha1 regulation of Hsp90 ATPase activity in maintaining proteostasis in the human disease cystic fibrosis. Mol Biol Cell. 2010;21:871-84 pubmed publisher
    The activator of Hsp90 ATPase 1, Aha1, has been shown to participate in the Hsp90 chaperone cycle by stimulating the low intrinsic ATPase activity of Hsp90...
  11. Weihofen A, Ostaszewski B, Minami Y, Selkoe D. Pink1 Parkinson mutations, the Cdc37/Hsp90 chaperones and Parkin all influence the maturation or subcellular distribution of Pink1. Hum Mol Genet. 2008;17:602-16 pubmed
    ..Using unbiased analyses of immunoisolated Pink1 complexes by mass spectrometry, co-immunoprecipitation and Hsp90 inhibitor studies, we identify Pink1 as a novel Cdc37/Hsp90 client kinase...
  12. Ko H, Bailey R, Smith W, Liu Z, Shin J, Lee Y, et al. CHIP regulates leucine-rich repeat kinase-2 ubiquitination, degradation, and toxicity. Proc Natl Acad Sci U S A. 2009;106:2897-902 pubmed publisher
    ..Moreover, HSP90 forms a complex with LRRK2, and inhibition of HSP90 chaperone activity by 17AAG leads to proteasomal degradation ..
  13. Vozzolo L, Loh B, Gane P, Tribak M, Zhou L, Anderson I, et al. Gyrase B inhibitor impairs HIV-1 replication by targeting Hsp90 and the capsid protein. J Biol Chem. 2010;285:39314-28 pubmed publisher
    ..Target discovery identified Hsp90 as the C-A1 target affecting viral gene expression...
  14. He F, Qiao Z, Cai J, Pierce W, He D, Song Z. Involvement of the 90-kDa heat shock protein (Hsp-90) in CB2 cannabinoid receptor-mediated cell migration: a new role of Hsp-90 in migration signaling of a G protein-coupled receptor. Mol Pharmacol. 2007;72:1289-300 pubmed
    ..and mass spectrometry-based proteomic approach, we first identified the 90-kDa heat shock protein (Hsp90), a chaperone protein with novel signaling functions, as a CB2-interacting protein...
  15. Kang G, Lee E, Jang K, Kim K, Park C, Lee C, et al. Expression of HSP90 in gastrointestinal stromal tumours and mesenchymal tumours. Histopathology. 2010;56:694-701 pubmed publisher
    Heat shock proteins (HSP) are up-regulated under conditions of increased stress, including cancer. Recently, HSP90 has been shown to be crucial to the expression and activation of the KIT oncoprotein...
  16. Mayor A, Martinon F, De Smedt T, Petrilli V, Tschopp J. A crucial function of SGT1 and HSP90 in inflammasome activity links mammalian and plant innate immune responses. Nat Immunol. 2007;8:497-503 pubmed
    ..we show that many NLRs interacted with the ubiquitin ligase-associated protein SGT1 and heat-shock protein 90 (HSP90), both of which have plant orthologs essential for R-protein responses...
  17. Shimp S, Chafin C, Regna N, Hammond S, Read M, Caudell D, et al. Heat shock protein 90 inhibition by 17-DMAG lessens disease in the MRL/lpr mouse model of systemic lupus erythematosus. Cell Mol Immunol. 2012;9:255-66 pubmed publisher
    Elevated expression of heat shock protein 90 (HSP90) has been found in kidneys and serum of systemic lupus erythematosus (SLE) patients and MRL/Mp-Fas(lpr)/Fas(lpr) (MRL/lpr) autoimmune mice...
  18. Cerchietti L, Lopes E, Yang S, Hatzi K, Bunting K, Tsikitas L, et al. A purine scaffold Hsp90 inhibitor destabilizes BCL-6 and has specific antitumor activity in BCL-6-dependent B cell lymphomas. Nat Med. 2009;15:1369-76 pubmed publisher
    We report that heat shock protein 90 (Hsp90) inhibitors selectively kill diffuse large B cell lymphomas (DLBCLs) that depend on the BCL-6 transcriptional repressor...
  19. Peterson L, Eskew J, Vielhauer G, Blagg B. The hERG channel is dependent upon the Hsp90? isoform for maturation and trafficking. Mol Pharm. 2012;9:1841-6 pubmed publisher
    Heat shock protein 90 (Hsp90) has emerged as a promising therapeutic target for the treatment of cancer. Several Hsp90 inhibitors have entered clinical trials...
  20. El Hamidieh A, Grammatikakis N, Patsavoudi E. Cell surface Cdc37 participates in extracellular HSP90 mediated cancer cell invasion. PLoS ONE. 2012;7:e42722 pubmed publisher
    ..is a 50 kDa molecular chaperone which targets intrinsically unstable protein kinases to the molecular chaperone HSP90. It is also an over-expressed oncoprotein that mediates carcinogenesis and maintenance of the malignant phenotype ..
  21. Flandrin P, Guyotat D, Duval A, Cornillon J, Tavernier E, Nadal N, et al. Significance of heat-shock protein (HSP) 90 expression in acute myeloid leukemia cells. Cell Stress Chaperones. 2008;13:357-64 pubmed publisher
    The 90-kDa heat shock protein (HSP90) is implicated in the conformational maturation and stabilization of a variety of client proteins with receptor and signal transduction functions...
  22. Millson S, Vaughan C, Zhai C, Ali M, Panaretou B, Piper P, et al. Chaperone ligand-discrimination by the TPR-domain protein Tah1. Biochem J. 2008;413:261-8 pubmed publisher
    ..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...
  23. Bergmayr C, Thurner P, Keuerleber S, Kudlacek O, Nanoff C, Freissmuth M, et al. Recruitment of a cytoplasmic chaperone relay by the A2A adenosine receptor. J Biol Chem. 2013;288:28831-44 pubmed publisher
    ..We identified molecular chaperones (heat-shock proteins HSP90? and HSP70-1A) that interact with and retain partially folded A2A receptor prior to ER exit...
  24. Wrighton K, Lin X, Feng X. Critical regulation of TGFbeta signaling by Hsp90. Proc Natl Acad Sci U S A. 2008;105:9244-9 pubmed publisher
    ..The 90-kDa heat-shock protein (Hsp90) is a molecular chaperone facilitating the folding and stabilization of many protein kinases and intracellular ..
  25. Morishima Y, Wang A, Yu Z, Pratt W, Osawa Y, Lieberman A. CHIP deletion reveals functional redundancy of E3 ligases in promoting degradation of both signaling proteins and expanded glutamine proteins. Hum Mol Genet. 2008;17:3942-52 pubmed publisher
    CHIP (carboxy terminus of Hsc70-interacting protein) an E3 ubiquitin ligase that binds to Hsp70 and Hsp90, promotes degradation of several Hsp90-regulated signaling proteins and disease-causing proteins containing expanded glutamine ..
  26. Wang X, Song X, Zhuo W, Fu Y, Shi H, Liang Y, et al. The regulatory mechanism of Hsp90alpha secretion and its function in tumor malignancy. Proc Natl Acad Sci U S A. 2009;106:21288-93 pubmed publisher
    ..In sum, our results reveal the regulatory mechanism of Hsp90alpha secretion, and its function in tumor invasiveness, indicating it can be a promising diagnostic marker for tumor malignancy in clinical application. ..
  27. Acquaviva J, Smith D, Jimenez J, Zhang C, Sequeira M, He S, et al. Overcoming acquired BRAF inhibitor resistance in melanoma via targeted inhibition of Hsp90 with ganetespib. Mol Cancer Ther. 2014;13:353-63 pubmed publisher
    ..Here, we examined the activity of ganetespib, a small-molecule inhibitor of Hsp90, in melanoma lines harboring the BRAF(V600E) mutation...
  28. Abu Farha M, Lambert J, Al Madhoun A, Elisma F, Skerjanc I, Figeys D. The tale of two domains: proteomics and genomics analysis of SMYD2, a new histone methyltransferase. Mol Cell Proteomics. 2008;7:560-72 pubmed
    ..Furthermore the combination of the SMYD2 interactome with the gene expression data suggests that some of the genes regulated by SMYD2 are closely associated with SMYD2-interacting proteins. ..
  29. Gopal U, Bohonowych J, Lema Tome C, Liu A, Garrett Mayer E, Wang B, et al. A novel extracellular Hsp90 mediated co-receptor function for LRP1 regulates EphA2 dependent glioblastoma cell invasion. PLoS ONE. 2011;6:e17649 pubmed publisher
    Extracellular Hsp90 protein (eHsp90) potentiates cancer cell motility and invasion through a poorly understood mechanism involving ligand mediated function with its cognate receptor LRP1...
  30. Wang L, Xie C, Greggio E, Parisiadou L, Shim H, Sun L, et al. The chaperone activity of heat shock protein 90 is critical for maintaining the stability of leucine-rich repeat kinase 2. J Neurosci. 2008;28:3384-91 pubmed publisher
    ..Here we show that LRRK2 forms a complex with heat shock protein 90 (Hsp90) in vivo and that inhibition of Hsp90 disrupts the association of Hsp90 with LRRK2 and leads to proteasomal ..
  31. Song C, Park S, Eom K, Kim J, Kim S, Kim J, et al. Potential prognostic value of heat-shock protein 90 in the presence of phosphatidylinositol-3-kinase overexpression or loss of PTEN, in invasive breast cancers. Breast Cancer Res. 2010;12:R20 pubmed publisher
    ..phospho-p70S6 kinase, phospho-S6 ribosomal protein, phospho-RAF, phospho-p44/42 MAPK, and heat-shock protein 90 (HSP90) were performed on tumor samples from 212 patients with invasive breast cancer...
  32. Zhang M, Boter M, Li K, Kadota Y, Panaretou B, Prodromou C, et al. Structural and functional coupling of Hsp90- and Sgt1-centred multi-protein complexes. EMBO J. 2008;27:2789-98 pubmed publisher
    ..ligases, the CBF3 kinetochore complex, plant R proteins and related animal Nod-like receptors, and with the Hsp90 molecular chaperone...
  33. Diehl M, Idowu M, Kimmelshue K, York T, Elmore L, Holt S. Elevated expression of nuclear Hsp90 in invasive breast tumors. Cancer Biol Ther. 2009;8:1952-61 pubmed
    ..To better define the role of chaperones in breast cancer, tissue arrays were immunostained for the chaperones Hsp90 and p23 and assessed in terms of reactivity, intensity and cellular localization...
  34. Pare J, Tahbaz N, López Orozco J, LaPointe P, Lasko P, Hobman T. Hsp90 regulates the function of argonaute 2 and its recruitment to stress granules and P-bodies. Mol Biol Cell. 2009;20:3273-84 pubmed publisher
    ..Furthermore, pharmacological inhibition of Hsp90 was associated with reduced microRNA- and short interfering RNA-dependent gene silencing...
  35. Kim R, Kim R, Chen W, Hu S, Shin K, Park N, et al. Association of hsp90 to the hTERT promoter is necessary for hTERT expression in human oral cancer cells. Carcinogenesis. 2008;29:2425-31 pubmed publisher
    ..Using DNA-protein-binding assay, we found that heat shock protein 90 (hsp90) physically interacts with the hTERT promoter in vitro...
  36. Ahsan A, Ramanand S, Whitehead C, Hiniker S, Rehemtulla A, Pratt W, et al. Wild-type EGFR is stabilized by direct interaction with HSP90 in cancer cells and tumors. Neoplasia. 2012;14:670-7 pubmed
    ..Heat shock protein 90 (HSP90) is known to stabilize mutant EGFR and ErbB2, but its role in cancers with wild-type (WT) WT-EGFR is unclear...
  37. Koizumi H, Yamada T, Takeuchi S, Nakagawa T, Kita K, Nakamura T, et al. Hsp90 inhibition overcomes HGF-triggering resistance to EGFR-TKIs in EGFR-mutant lung cancer by decreasing client protein expression and angiogenesis. J Thorac Oncol. 2012;7:1078-85 pubmed publisher
    ..Heat shock protein90 (Hsp90) is a 90 kDa molecular chaperone for proteins that include EGFR, Met, and echinoderm microtubule-associated ..
  38. Donnelly B, Needham P, Snyder A, Roy A, Khadem S, Brodsky J, et al. Hsp70 and Hsp90 multichaperone complexes sequentially regulate thiazide-sensitive cotransporter endoplasmic reticulum-associated degradation and biogenesis. J Biol Chem. 2013;288:13124-35 pubmed publisher
    ..Analyses of NCC immunoprecipitates revealed that the cotransporter formed complexes with the core chaperones Hsp90, Hsp70, and Hsp40...
  39. Shimamura T, Perera S, Foley K, Sang J, Rodig S, Inoue T, et al. Ganetespib (STA-9090), a nongeldanamycin HSP90 inhibitor, has potent antitumor activity in in vitro and in vivo models of non-small cell lung cancer. Clin Cancer Res. 2012;18:4973-85 pubmed publisher
    We describe the anticancer activity of ganetespib, a novel non-geldanamycin heat shock protein 90 (HSP90) inhibitor, in non-small cell lung cancer (NSCLC) models.
  40. Wang J, Cui S, Zhang X, Wu Y, Tang H. High expression of heat shock protein 90 is associated with tumor aggressiveness and poor prognosis in patients with advanced gastric cancer. PLoS ONE. 2013;8:e62876 pubmed publisher
    The heat shock protein 90 (HSP90) is overexpressed and highly associated with poor prognosis in many malignancies. However, the role of HSP90 in gastric cancer has not been thoroughly elucidated...
  41. Stecklein S, Kumaraswamy E, Behbod F, Wang W, Chaguturu V, HARLAN WILLIAMS L, et al. BRCA1 and HSP90 cooperate in homologous and non-homologous DNA double-strand-break repair and G2/M checkpoint activation. Proc Natl Acad Sci U S A. 2012;109:13650-5 pubmed publisher
    ..We demonstrate that the heat-shock protein 90 (HSP90) inhibitor 17-allylamino-17-demethoxygeldanamycin [17-AAG (Tanespimycin)], currently in Phase II/III clinical ..
  42. Shimamoto S, Kubota Y, Tokumitsu H, Kobayashi R. S100 proteins regulate the interaction of Hsp90 with Cyclophilin 40 and FKBP52 through their tetratricopeptide repeats. FEBS Lett. 2010;584:1119-25 pubmed publisher
    ..These immunophilins contain a tetratricopeptide repeat (TPR) domain for Hsp90 binding...
  43. Taipale M, Krykbaeva I, Koeva M, Kayatekin C, Westover K, Karras G, et al. Quantitative analysis of HSP90-client interactions reveals principles of substrate recognition. Cell. 2012;150:987-1001 pubmed publisher
    b>HSP90 is a molecular chaperone that associates with numerous substrate proteins called clients...
  44. Dachsel J, Taylor J, Mok S, Ross O, Hinkle K, Bailey R, et al. Identification of potential protein interactors of Lrrk2. Parkinsonism Relat Disord. 2007;13:382-5 pubmed
    ..Future investigation of these candidates is now warranted and may help resolve the pathomechanism behind Lrrk2 neurodegeneration. ..
  45. Giustiniani J, Daire V, Cantaloube I, Durand G, Poüs C, Perdiz D, et al. Tubulin acetylation favors Hsp90 recruitment to microtubules and stimulates the signaling function of the Hsp90 clients Akt/PKB and p53. Cell Signal. 2009;21:529-39 pubmed publisher
    ..The molecular chaperone Hsp90, which is essential for the folding and activity of numerous client proteins involved in cell proliferation and ..
  46. Gallegos Ruiz M, Floor K, Roepman P, Rodriguez J, Meijer G, Mooi W, et al. Integration of gene dosage and gene expression in non-small cell lung cancer, identification of HSP90 as potential target. PLoS ONE. 2008;3:e0001722 pubmed publisher
    ..2-33 as a common alteration in NSCLC (44%), which significantly influenced gene expression for HSP90, residing on 14q32. This deletion was correlated with better overall survival (P = 0...
  47. Gano J, Simon J. A proteomic investigation of ligand-dependent HSP90 complexes reveals CHORDC1 as a novel ADP-dependent HSP90-interacting protein. Mol Cell Proteomics. 2010;9:255-70 pubmed publisher
    Structural studies of the chaperone HSP90 have revealed that nucleotide and drug ligands induce several distinct conformational states; however, little is known how these conformations affect interactions with co-chaperones and client ..
  48. Xia T, Dimitropoulou C, Zeng J, Antonova G, Snead C, Venema R, et al. Chaperone-dependent E3 ligase CHIP ubiquitinates and mediates proteasomal degradation of soluble guanylyl cyclase. Am J Physiol Heart Circ Physiol. 2007;293:H3080-7 pubmed
    ..Inhibition of HSP90 by geldanamycin causes proteasomal degradation of sGC protein...
  49. Park J, Kim S, Choi M, Lee J, Oh D, Im S, et al. Class II histone deacetylases play pivotal roles in heat shock protein 90-mediated proteasomal degradation of vascular endothelial growth factor receptors. Biochem Biophys Res Commun. 2008;368:318-22 pubmed publisher
    ..However, we noted no remarkable changes in the binding of Hsp90/Hsp70 to VEGFR3. HDI treatment effectively inhibited the activities of HDAC6 and HDAC10...
  50. Zagouri F, Nonni A, Sergentanis T, Papadimitriou C, Michalopoulos N, Lazaris A, et al. Heat shock protein90 in lobular neoplasia of the breast. BMC Cancer. 2008;8:312 pubmed publisher
    Heat shock protein 90 (Hsp90) overexpression has been implicated in breast carcinogenesis, with putative prognostic and therapeutic implications...
  51. Wu X, Wanders A, Wardega P, Tinge B, Gedda L, Bergstrom S, et al. Hsp90 is expressed and represents a therapeutic target in human oesophageal cancer using the inhibitor 17-allylamino-17-demethoxygeldanamycin. Br J Cancer. 2009;100:334-43 pubmed publisher
    Heat shock protein 90 (Hsp90) has been demonstrated to protect oncogenic variants of signalling molecules from degradation and may consequently serve as a therapeutic target for the treatment of oesophageal cancer for which adequate ..
  52. Ding X, Goldberg M. Regulation of LRRK2 stability by the E3 ubiquitin ligase CHIP. PLoS ONE. 2009;4:e5949 pubmed publisher
    ..We further show that LRRK2 forms a complex with overexpressed and endogenous CHIP and Hsp90. Our data indicates that the destabilization of LRRK2 by CHIP is due to ubiquitination and proteasome-dependent ..
  53. Lang S, Moser C, Gaumann A, Klein D, Glockzin G, Popp F, et al. Targeting heat shock protein 90 in pancreatic cancer impairs insulin-like growth factor-I receptor signaling, disrupts an interleukin-6/signal-transducer and activator of transcription 3/hypoxia-inducible factor-1alpha autocrine loop, and reduces ort. Clin Cancer Res. 2007;13:6459-68 pubmed
    Inhibitors of heat-shock protein 90 (Hsp90) may interfere with oncogenic signaling pathways, including Erk, Akt, and hypoxia-inducible factor-1alpha (HIF-1alpha)...
  54. Ni L, Yang C, Gioeli D, Frierson H, Toft D, Paschal B. FKBP51 promotes assembly of the Hsp90 chaperone complex and regulates androgen receptor signaling in prostate cancer cells. Mol Cell Biol. 2010;30:1243-53 pubmed publisher
    ..Here, we report that the Hsp90 cochaperone FKBP51 is upregulated in LAPC-4 AI tumors grown in castrated mice and describe a molecular mechanism ..
  55. Shimamoto S, Kubota Y, Yamaguchi F, Tokumitsu H, Kobayashi R. Ca2+/S100 proteins act as upstream regulators of the chaperone-associated ubiquitin ligase CHIP (C terminus of Hsc70-interacting protein). J Biol Chem. 2013;288:7158-68 pubmed publisher
    The U-box E3 ubiquitin ligase CHIP (C terminus of Hsc70-interacting protein) binds Hsp90 and/or Hsp70 via its tetratricopeptide repeat (TPR), facilitating ubiquitination of the chaperone-bound client proteins...
  56. Li D, Marchenko N, Schulz R, Fischer V, Velasco Hernandez T, Talos F, et al. Functional inactivation of endogenous MDM2 and CHIP by HSP90 causes aberrant stabilization of mutant p53 in human cancer cells. Mol Cancer Res. 2011;9:577-88 pubmed publisher
    ..wild-type p53, the many mutant p53 proteins which are conformationally aberrant are engaged in complexes with the HSP90 chaperone machinery to prevent its aggregation...
  57. Milicevic Z, Bogojevic D, Mihailovic M, Petrovic M, Krivokapic Z. Molecular characterization of hsp90 isoforms in colorectal cancer cells and its association with tumour progression. Int J Oncol. 2008;32:1169-78 pubmed
    ..As determined by Western blot assay all hsp90 isoforms studied, alpha (84 kDa), beta (86 kDa) and hsp90N (75 kDa), were up-regulated and differentially expressed in various stages of colorectal carcinoma...
  58. Hinz M, Broemer M, Arslan S, Otto A, Mueller E, Dettmer R, et al. Signal responsiveness of IkappaB kinases is determined by Cdc37-assisted transient interaction with Hsp90. J Biol Chem. 2007;282:32311-9 pubmed
    ..Heat shock protein 90 (Hsp90) and the co-chaperone Cdc37 have been indicated as additional subunits, but their specific functions in signal ..
  59. Onuoha S, Coulstock E, Grossmann J, Jackson S. Structural studies on the co-chaperone Hop and its complexes with Hsp90. J Mol Biol. 2008;379:732-44 pubmed publisher
    ..protein (Hop) plays a critical role in mediating interactions between Heat Shock Protein (Hsp)70 and Hsp90 as part of the cellular assembly machine...
  60. Huntoon C, Nye M, Geng L, Peterson K, Flatten K, Haluska P, et al. Heat shock protein 90 inhibition depletes LATS1 and LATS2, two regulators of the mammalian hippo tumor suppressor pathway. Cancer Res. 2010;70:8642-50 pubmed publisher
    Heat shock protein 90 (HSP90), which regulates the functions of multiple oncogenic signaling pathways, has emerged as a novel anticancer therapeutic target, and multiple small-molecule HSP90 inhibitors are now in clinical trials...
  61. Vaughan C, Mollapour M, Smith J, Truman A, Hu B, Good V, et al. Hsp90-dependent activation of protein kinases is regulated by chaperone-targeted dephosphorylation of Cdc37. Mol Cell. 2008;31:886-95 pubmed publisher
    Activation of protein kinase clients by the Hsp90 system is mediated by the cochaperone protein Cdc37. Cdc37 requires phosphorylation at Ser13, but little is known about the regulation of this essential posttranslational modification...
  62. Felts S, Karnitz L, Toft D. Functioning of the Hsp90 machine in chaperoning checkpoint kinase I (Chk1) and the progesterone receptor (PR). Cell Stress Chaperones. 2007;12:353-63 pubmed
    b>Hsp90 is an abundant and highly conserved chaperone that functions at later stages of protein folding to maintain and regulate the activity of client proteins...
  63. Schulz R, Marchenko N, Holembowski L, Fingerle Rowson G, Pesic M, Zender L, et al. Inhibiting the HSP90 chaperone destabilizes macrophage migration inhibitory factor and thereby inhibits breast tumor progression. J Exp Med. 2012;209:275-89 pubmed publisher
    ..We show that the tumor-activated HSP90 chaperone complex protects MIF from degradation...
  64. Qin Z, DEFEE M, Isaacs J, Parsons C. Extracellular Hsp90 serves as a co-factor for MAPK activation and latent viral gene expression during de novo infection by KSHV. Virology. 2010;403:92-102 pubmed publisher
    ..Using a recently characterized non-permeable inhibitor specifically targeting csHsp90 and Hsp90-specific antibodies, we show that csHsp90 inhibition suppresses KSHV gene expression during de novo infection, and ..
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    ..Our data indicate that hsp90alpha is released by invasive cancer cells via exosomes and implicates hsp90alpha in activating plasmin, a second protease that acts in cancer cell invasion. ..
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    Tetratricopeptide repeat (TPR) motif containing co-chaperones of the chaperone Hsp90 are considered control modules that govern activity and specificity of this central folding platform. Steroid receptors are paradigm clients of Hsp90...
  67. Kundrat L, Regan L. Balance between folding and degradation for Hsp90-dependent client proteins: a key role for CHIP. Biochemistry. 2010;49:7428-38 pubmed publisher
    ..the results of an investigation of the balance between protein folding and degradation for mammalian chaperone Hsp90-dependent client proteins...
  68. Horejsi Z, Takai H, Adelman C, Collis S, Flynn H, Maslen S, et al. CK2 phospho-dependent binding of R2TP complex to TEL2 is essential for mTOR and SMG1 stability. Mol Cell. 2010;39:839-50 pubmed publisher
    ..Although the CK2 phosphosite mutant of TEL2 retains association with the PIKKs and HSP90 in cells, failure to interact with the R2TP/prefoldin-like complex results in instability of the PIKKs, ..