Genomes and Genes
hsp90 heat shock proteins
Summary: A class of MOLECULAR CHAPERONES whose members act in the mechanism of SIGNAL TRANSDUCTION by STEROID RECEPTORS.
- Usmani S, Bona R, Li Z. 17 AAG for HSP90 inhibition in cancer--from bench to bedside. Curr Mol Med. 2009;9:654-64 pubmed
- Brough P, Barril X, Borgognoni J, Chene P, Davies N, Davis B, et al. Combining hit identification strategies: fragment-based and in silico approaches to orally active 2-aminothieno[2,3-d]pyrimidine inhibitors of the Hsp90 molecular chaperone. J Med Chem. 2009;52:4794-809 pubmed publisher..Several examples (34a, 34d and 34i) caused tumor growth regression at well tolerated doses when administered orally in a human BT474 human breast cancer xenograft model. ..
- Baselga J, Swain S. Novel anticancer targets: revisiting ERBB2 and discovering ERBB3. Nat Rev Cancer. 2009;9:463-75 pubmed publisher..These new therapies include tyrosine kinase inhibitors, antibody-chemotherapy conjugates, heat-shock protein inhibitors and antibodies that interfere with the formation of ERBB2-ERBB3 dimers. ..
- Bao R, Lai C, Qu H, Wang D, Yin L, Zifcak B, et al. CUDC-305, a novel synthetic HSP90 inhibitor with unique pharmacologic properties for cancer therapy. Clin Cancer Res. 2009;15:4046-57 pubmed publisher..CUDC-305 is a promising drug candidate for the treatment of a variety of cancers, including brain malignancies. ..
- Shelton S, Shawgo M, Matthews S, Lu Y, Donnelly A, Szabla K, et al. KU135, a novel novobiocin-derived C-terminal inhibitor of the 90-kDa heat shock protein, exerts potent antiproliferative effects in human leukemic cells. Mol Pharmacol. 2009;76:1314-22 pubmed publisher..Together, these data suggest that KU135 inhibits cell proliferation by regulating signaling pathways that are mechanistically different from those targeted by 17-AAG and as such represents a novel opportunity for Hsp90 inhibition. ..
- Walerych D, Olszewski M, Gutkowska M, Helwak A, Zylicz M, Zylicz A. Hsp70 molecular chaperones are required to support p53 tumor suppressor activity under stress conditions. Oncogene. 2009;28:4284-94 pubmed publisher..Our results indicate for the first time that, especially under stress conditions, not only Hsp90 but also Hsp70 is required for the chaperoning of WT and R249S p53. ..
- van De Sluis B, Groot A, Vermeulen J, van der Wall E, van Diest P, Wijmenga C, et al. COMMD1 Promotes pVHL and O2-Independent Proteolysis of HIF-1alpha via HSP90/70. PLoS ONE. 2009;4:e7332 pubmed publisher..These data reveal a novel role for COMMD1 in conjunction with HSP90beta/HSP70 in the ubiquitin and O(2)-independent regulation of HIF-1alpha. ..
- Him N, Gillan V, Emes R, Maitland K, Devaney E. Hsp-90 and the biology of nematodes. BMC Evol Biol. 2009;9:254 pubmed publisher..Factors other than primary amino acid sequence may influence the ability of Hsp-90 to bind to geldanamycin. ..
- Taldone T, Chiosis G. Purine-scaffold Hsp90 inhibitors. Curr Top Med Chem. 2009;9:1436-46 pubmed..Their potential towards neurodegenerative diseases will also be touched upon. ..
- Specchia V, Piacentini L, Tritto P, Fanti L, D Alessandro R, Palumbo G, et al. Hsp90 prevents phenotypic variation by suppressing the mutagenic activity of transposons. Nature. 2010;463:662-5 pubmed publisher..This indicates that Hsp90 mutations can generate new variation by transposon-mediated 'canonical' mutagenesis. ..
- Day J, Sharp S, Rowlands M, Aherne W, Workman P, Moody C. Targeting the Hsp90 chaperone: synthesis of novel resorcylic acid macrolactone inhibitors of Hsp90. Chemistry. 2010;16:2758-63 pubmed publisher..The methodology has been extended to a novel series of macrolactones incorporating a 1,2,3-triazole ring. ..
- Clark C, Rane M, El Mehdi D, Miller C, Sachleben L, Gozal E. Role of oxidative stress in geldanamycin-induced cytotoxicity and disruption of Hsp90 signaling complex. Free Radic Biol Med. 2009;47:1440-9 pubmed publisher..These differences between MEN- and GA-induced cytotoxicity may allow more specific targeting of cancer cells. ..
- 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..Together, our data suggest that Hsp90 is a critical modulator of Argonaute function. Moreover, we propose that Ago2 and PACT form a complex that functions at the level of SGs. ..
- Shirasu K. The HSP90-SGT1 chaperone complex for NLR immune sensors. Annu Rev Plant Biol. 2009;60:139-64 pubmed publisher..Deciphering how the chaperone machinery works would facilitate an understanding of the mechanisms of pathogen recognition and signal transduction by NLR proteins in both plants and animals. ..
- Hessling M, Richter K, Buchner J. Dissection of the ATP-induced conformational cycle of the molecular chaperone Hsp90. Nat Struct Mol Biol. 2009;16:287-93 pubmed publisher..This comprehensive reconstitution of the Hsp90 cycle defines a controlled progression through distinct intermediates that can be modulated by conformation-sensitive cochaperones. ..
- Taldone T, Sun W, Chiosis G. Discovery and development of heat shock protein 90 inhibitors. Bioorg Med Chem. 2009;17:2225-35 pubmed publisher..This review will discuss the discovery of these different classes, as well as their development as potential clinical agents. ..
- Mickler M, Hessling M, Ratzke C, Buchner J, Hugel T. The large conformational changes of Hsp90 are only weakly coupled to ATP hydrolysis. Nat Struct Mol Biol. 2009;16:281-6 pubmed publisher..Unexpectedly, in this model ATP lowers two energy barriers almost symmetrically, such that little directionality is introduced. Instead, stochastic, thermal fluctuations of Hsp90 are the dominating processes. ..
- Prodromou C, Nuttall J, Millson S, Roe S, Sim T, Tan D, et al. Structural basis of the radicicol resistance displayed by a fungal hsp90. ACS Chem Biol. 2009;4:289-97 pubmed publisher..To the best of our knowledge, this is the first demonstration that it is possible for Hsp90 inhibitor resistance to arise by subtle alteration to the structure of Hsp90 itself. ..
- Shapiro R, Uppuluri P, Zaas A, Collins C, Senn H, Perfect J, et al. Hsp90 orchestrates temperature-dependent Candida albicans morphogenesis via Ras1-PKA signaling. Curr Biol. 2009;19:621-9 pubmed publisher..Hsp90's capacity to govern a key developmental program in response to temperature change provides a new mechanism that complements the elegant repertoire that organisms utilize to sense temperature. ..
- Krukenberg K, Förster F, Rice L, Sali A, Agard D. Multiple conformations of E. coli Hsp90 in solution: insights into the conformational dynamics of Hsp90. Structure. 2008;16:755-65 pubmed publisher..These studies provide a unique view of Hsp90 conformational dynamics and provide a model for the role of nucleotide in effecting conformational change. ..
- Gaspar N, Sharp S, Pacey S, Jones C, Walton M, Vassal G, et al. Acquired resistance to 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin) in glioblastoma cells. Cancer Res. 2009;69:1966-75 pubmed publisher..In conclusion, low NQO1 activity is a likely mechanism of acquired resistance to 17-AAG in GB, melanoma, and, possibly, other tumor types. Such resistance can be overcome with novel HSP90 inhibitors. ..
- Wang S, Chuang J, Yeh S, Wang Y, Liu Y, Chang W, et al. Heat shock protein 90 is important for Sp1 stability during mitosis. J Mol Biol. 2009;387:1106-19 pubmed publisher..Taken together, Hsp90 is important for maintaining Sp1 stability during mitosis by the JNK-1-mediated phosphorylation of Sp1 to enable division into daughter cells and to regulate the expression of related genes in the interphase. ..
- Hacker S, Lambers C, Hoetzenecker K, Pollreisz A, Aigner C, Lichtenauer M, et al. Elevated HSP27, HSP70 and HSP90 alpha in chronic obstructive pulmonary disease: markers for immune activation and tissue destruction. Clin Lab. 2009;55:31-40 pubmed..This is the first study to demonstrate elevated serum levels of the described heat shock proteins in patients with COPD. We showed sensitivity and specificity of serum HSP27 and HSP70 as diagnostic markers for COPD. ..
- Gillan V, Maitland K, McCormack G, Him N, Devaney E. Functional genomics of hsp-90 in parasitic and free-living nematodes. Int J Parasitol. 2009;39:1071-81 pubmed publisher..These results indicate that factors other than the level of sequence identity are important for determining whether parasite genes can functionally complement in C. elegans...
- Caldas Lopes E, Cerchietti L, Ahn J, Clement C, Robles A, Rodina A, et al. Hsp90 inhibitor PU-H71, a multimodal inhibitor of malignancy, induces complete responses in triple-negative breast cancer models. Proc Natl Acad Sci U S A. 2009;106:8368-73 pubmed publisher..The results identify Hsp90 as a critical and multimodal target in this most difficult to treat breast cancer subtype and support the use of the Hsp90 inhibitor PU-H71 for clinical trials involving patients with TNBC. ..
- Shen H, Zhao Y, Chen X, Xiong R, Lu J, Chen J, et al. Differential alteration of heat shock protein 90 in mice modifies glucocorticoid receptor function and susceptibility to trauma. J Neurotrauma. 2010;27:373-81 pubmed publisher..Thus, pharmacological manipulation of Hsp90 may represent a therapeutic strategy to modify the function of the GC-GR pathway and traumatic stress response. ..
- Napper A. Society for biomolecular sciences - 16th annual conference & exhibition - advancing the science of drug discovery. IDrugs. 2010;13:372-5 pubmed..Investigational drugs discussed include GDC-0941 (Genentech Inc), NVP-AUY-922 (Novartis AG) and olaparib (AstraZeneca). ..
- Fleming I. Molecular mechanisms underlying the activation of eNOS. Pflugers Arch. 2010;459:793-806 pubmed publisher..This review summarizes some of the recent findings relating to the molecular events regulating eNOS activity. ..
- Musicki B, Liu T, Strong T, Lagoda G, Bivalacqua T, Burnett A. Post-translational regulation of endothelial nitric oxide synthase (eNOS) by estrogens in the rat vagina. J Sex Med. 2010;7:1768-77 pubmed publisher..These results define novel estrogen signaling mechanisms in the vagina which involve eNOS phosphorylation and eNOS-caveolin-1 interaction. ..
- Mittelman D, Sykoudis K, Hersh M, Lin Y, Wilson J. Hsp90 modulates CAG repeat instability in human cells. Cell Stress Chaperones. 2010;15:753-9 pubmed publisher..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. ..
- Yang Y, Yan X, Cai Y, Lu Y, Si J, Zhou T. NudC-like protein 2 regulates the LIS1/dynein pathway by stabilizing LIS1 with Hsp90. Proc Natl Acad Sci U S A. 2010;107:3499-504 pubmed publisher..Thus, our results suggest that NudCL2 regulates the LIS1/dynein pathway by stabilizing LIS1 with Hsp90 chaperone. This represents a hitherto undescribed mechanism of the LIS1/dynein regulation in mammalian cells. ..
- Nakashima T, Ishii T, Tagaya H, Seike T, Nakagawa H, Kanda Y, et al. New molecular and biological mechanism of antitumor activities of KW-2478, a novel nonansamycin heat shock protein 90 inhibitor, in multiple myeloma cells. Clin Cancer Res. 2010;16:2792-802 pubmed publisher..These results suggest that targeting such diverse pathways by KW-2478 could be a promising strategy for the treatment of MM with various cytogenetic abnormalities. ..
- Day J, Sharp S, Rowlands M, Aherne W, Lewis W, Roe S, et al. Inhibition of Hsp90 with resorcylic acid macrolactones: synthesis and binding studies. Chemistry. 2010;16:10366-72 pubmed publisher..As a result of this conformational change, the compounds bound less favorably to Hsp90. ..
- Bandyopadhyay S, Chiang C, Srivastava J, Gersten M, White S, Bell R, et al. A human MAP kinase interactome. Nat Methods. 2010;7:801-5 pubmed..This study makes available a large resource of MAPK interactions and clone libraries, and it illustrates a methodology for probing signaling networks based on functional refinement of experimentally derived protein-interaction maps. ..
- Sloan L, Fillmore M, Churcher I. Small-molecule modulation of cellular chaperones to treat protein misfolding disorders. Curr Opin Drug Discov Devel. 2009;12:666-81 pubmed
- Nanduri J, Bergson P, Wang N, Ficker E, Prabhakar N. Hypoxia inhibits maturation and trafficking of hERG K(+) channel protein: Role of Hsp90 and ROS. Biochem Biophys Res Commun. 2009;388:212-6 pubmed publisher..These results demonstrate that ROS generated during hypoxia prevents maturation of the hERG protein by inhibiting Hsp90 interaction resulting in decreased protein expression and currents. ..
- Burcham P, Raso A, Thompson C. Intermediate filament carbonylation during acute acrolein toxicity in A549 lung cells: functional consequences, chaperone redistribution, and protection by bisulfite. Antioxid Redox Signal. 2010;12:337-47 pubmed publisher..These novel observations identify intermediate filaments as key targets for the reactive smoke constituent acrolein. ..
- Narayan V, Eckert M, Zylicz A, Zylicz M, Ball K. Cooperative regulation of the interferon regulatory factor-1 tumor suppressor protein by core components of the molecular chaperone machinery. J Biol Chem. 2009;284:25889-99 pubmed publisher..This study begins to elucidate the role of the Mf1 domain of IRF-1 in orchestrating the recruitment of regulatory factors that can impact on both its turnover and transcriptional activity. ..
- Lewis S, Hutchinson M, Rezvani N, Loram L, Zhang Y, Maier S, et al. Evidence that intrathecal morphine-3-glucuronide may cause pain enhancement via toll-like receptor 4/MD-2 and interleukin-1beta. Neuroscience. 2010;165:569-83 pubmed publisher..These data provide the first evidence for a TLR4 and IL-1 mediated component to M3G-induced effects, likely of at least microglial origin. ..
- Matts R, Manjarrez J. Assays for identification of Hsp90 inhibitors and biochemical methods for discriminating their mechanism of action. Curr Top Med Chem. 2009;9:1462-78 pubmed
- Benoit J, Lopez Martinez G, Teets N, Phillips S, Denlinger D. Responses of the bed bug, Cimex lectularius, to temperature extremes and dehydration: levels of tolerance, rapid cold hardening and expression of heat shock proteins. Med Vet Entomol. 2009;23:418-25 pubmed publisher..Our results define the tolerance limits for bed bugs to these commonly encountered stresses of temperature and low humidity and indicate a role for Hsps in responding to these stresses. ..
- Kaiser M, Lamottke B, Mieth M, Jensen M, Quadt C, Garcia Echeverria C, et al. Synergistic action of the novel HSP90 inhibitor NVP-AUY922 with histone deacetylase inhibitors, melphalan, or doxorubicin in multiple myeloma. Eur J Haematol. 2010;84:337-44 pubmed publisher..These data show impressive synergistic action of the novel HSP90 inhibitor NVP-AUY922 with melphalan, doxorubicin, NVP-LBH589, and SAHA in multiple myeloma and build the frame work for clinical trials. ..
- Audisio D, Messaoudi S, Ijjaali I, Dubus E, Petitet F, Peyrat J, et al. Assessing the chemical diversity of an hsp90 database. Eur J Med Chem. 2010;45:2000-9 pubmed publisher..Furthermore, a fragment-based study highlighted the most frequently moieties represented in the active purine and pyrazole-isoxazole derivatives that are likely to be responsible for the observed biological activities. ..
- McKeen H, Byrne C, Jithesh P, Donley C, Valentine A, Yakkundi A, et al. FKBPL regulates estrogen receptor signaling and determines response to endocrine therapy. Cancer Res. 2010;70:1090-100 pubmed publisher..Our findings suggest that FKBPL may have prognostic value based on its impact on tumor proliferative capacity and sensitivity to endocrine therapies, which improve outcome. ..
- Suzuki S, Kulkarni A. Extracellular heat shock protein HSP90beta secreted by MG63 osteosarcoma cells inhibits activation of latent TGF-beta1. Biochem Biophys Res Commun. 2010;398:525-31 pubmed publisher..Thus, extracellular HSP90beta is a negative regulator for the activation of latent TGF-beta1 modulating TGF-beta signaling in the extracellular domain. ..
- Noguchi T, Makino S, Matsumoto R, Nakayama S, Nishiyama M, Terada Y, et al. Regulation of glucocorticoid receptor transcription and nuclear translocation during single and repeated immobilization stress. Endocrinology. 2010;151:4344-55 pubmed publisher..The reduced nuclear translocation of GR in the hippocampus during rIMO may reflect decreased glucocorticoid-mediated negative feedback on the hypothalamic-pituitary-adrenocortical axis. ..
- Banz V, Medová M, Keogh A, Furer C, Zimmer Y, Candinas D, et al. Hsp90 transcriptionally and post-translationally regulates the expression of NDRG1 and maintains the stability of its modifying kinase GSK3beta. Biochim Biophys Acta. 2009;1793:1597-603 pubmed publisher..Finally, we suggest for the first time GSK3beta as a new client protein of Hsp90. ..
- Palacios C, Martín Pérez R, López Pérez A, Pandiella A, Lopez Rivas A. Autophagy inhibition sensitizes multiple myeloma cells to 17-dimethylaminoethylamino-17-demethoxygeldanamycin-induced apoptosis. Leuk Res. 2010;34:1533-8 pubmed publisher..The potential use of Hsp90 and autophagy inhibitors combinations as a therapeutic tool in MM is further discussed in our work. ..
- Lagarrigue F, Dupuis Coronas S, Ramel D, Delsol G, Tronchère H, Payrastre B, et al. Matrix metalloproteinase-9 is upregulated in nucleophosmin-anaplastic lymphoma kinase-positive anaplastic lymphomas and activated at the cell surface by the chaperone heat shock protein 90 to promote cell invasion. Cancer Res. 2010;70:6978-87 pubmed publisher..They also point out new factors crucial for ALK(+) ALCL. ..