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No stress – Hsp90 and signal transduction in Leishmania

Published online by Cambridge University Press:  04 April 2014

A. HOMBACH  and
J. CLOS
A. HOMBACH
Affiliation:
Bernhard Nocht Institute for Tropical Medicine, Bernhard Nocht St. 74, 20359 Hamburg, Germany
J. CLOS*
Affiliation:
Bernhard Nocht Institute for Tropical Medicine, Bernhard Nocht St. 74, 20359 Hamburg, Germany
*
* Corresponding author:Bernhard Nocht Institute for Tropical Medicine, Bernhard Nocht St 74, 20359 Hamburg, Germany. E-mail: clos@bnitm.de
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Summary

Hsp90 (a.k.a. Hsp83) plays a significant role in the life cycle control of the protozoan parasite Leishmania donovani. Rather than protecting Leishmania spp. against adverse and stressful environs, Hsp90 is required for the maintenance of the motile, highly proliferative insect stage, the promastigote. However, Hsp90 is also essential for survival and proliferation of the intracellular mammalian stage, the amastigote. Moreover, recent evidence shows Hsp90 and other components of large multi-chaperone complexes as substrates of stage-specific protein phosphorylation pathways, and thus as likely effectors of the signal transduction pathways in Leishmania spp. Future efforts should be directed towards the identification of the protein kinases and the critical phosphorylation sites as targets for novel therapeutic approaches.

Keywords

LeishmaniaHsp90heat shocksignal transductionradicicol
Type
Special Issue Article
Information
Parasitology , Volume 141 , Special Issue 9: Heat shock proteins as drug targets in infectious diseases , August 2014 , pp. 1156 - 1166
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Copyright
Copyright © Cambridge University Press 2014 

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References

Alexandratos, A., Clos, J., Samiotaki, M., Efstathiou, A., Panayotou, G., Soteriadou, K. and Smirlis, D. (2013). Restoration of heat shock protein 83 expression in histone H1 over-expressing Leishmania donovani attenuated parasites identifies HSP83 as a virulence factor. Molecular Microbiology 88, 1015–1031. doi: 10.1111/mmi.12240.CrossRefGoogle Scholar
Alvar, J., Velez, I. D., Bern, C., Herrero, M., Desjeux, P., Cano, J., Jannin, J. and den Boer, M. (2012). Leishmaniasis worldwide and global estimates of its incidence. PloS One 7, e35671. doi: 10.1371/journal.pone.0035671.Google Scholar
Argaman, M., Aly, R. and Shapira, M. (1994). Expression of heat shock protein 83 in Leishmania is regulated post-transcriptionally. Molecular and Biochemical Parasitology 64, 95–110.Google Scholar
Banumathy, G., Singh, V., Pavithra, S. R. and Tatu, U. (2003). Heat shock protein 90 function is essential for Plasmodium falciparum growth in human erythrocytes. Journal of Biological Chemistry 278, 18336–18345. doi: 10.1074/jbc.M211309200.Google Scholar
Barak, E., Amin-Spector, S., Gerliak, E., Goyard, S., Holland, N. and Zilberstein, D. (2005). Differentiation of Leishmania donovani in host-free system: analysis of signal perception and response. Molecular and Biochemical Parasitology 141, 99–108.CrossRefGoogle ScholarPubMed
Bates, P. A. (1993). Axenic amastigote culture of Leishmania amastigotes. Parasitology Today 9, 143–146.Google Scholar
Bates, P. A. (1994). Complete developmental cycle of Leishmania mexicana in axenic culture. Parasitology 108, 1–9.Google Scholar
Bates, P. A., Cobertson, C. D., Tetley, L. and Coombs, G. H. (1992). Axenic cultivation and characterization of Leishmania mexicana amastigote-like forms. Parasitology 105, 193–202.Google Scholar
Bente, M., Harder, S., Wiesgigl, M., Heukeshoven, J., Gelhaus, C., Krause, E., Clos, J. and Bruchhaus, I. (2003). Developmentally induced changes of the proteome in the protozoan parasite Leishmania donovani . Proteomics 3, 1811–1829.Google Scholar
Brandau, S., Dresel, A. and Clos, J. (1995). High constitutive levels of heat-shock proteins in human-pathogenic parasites of the genus Leishmania. Biochemical Journal 310, 225–232.Google Scholar
Brochu, C., Haimeur, A. and Ouellette, M. (2004). The heat shock protein HSP70 and heat shock cognate protein HSC70 contribute to antimony tolerance in the protozoan parasite leishmania. Cell Stress and Chaperones 9, 294–303.Google Scholar
Buchner, J. (1999). Hsp90 & Co. – a holding for folding. Trends in Biochemical Sciences 24, 136–141.Google Scholar
Catelli, M. G., Binart, N., Jung-Testas, I., Renoir, J. M., Baulieu, E. E., Feramisco, J. R. and Welch, W. J. (1985). The common 90-kd protein component of non-transformed ‘8S’ steroid receptors is a heat-shock protein. EMBO Journal 4, 3131–3135.Google Scholar
Charest, H. and Matlashewski, G. (1994). Developmental gene expression in Leishmania donovani: differential cloning and analysis of an amastigote-stage-specific gene. Molecular and Cellular Biology 14, 2975–2984.Google ScholarPubMed
Charest, H., Zhang, W.-W. and Matlashewski, G. (1996). The developmental expression of Leishmania donovani A2 amastigote-specific genes is post-transcriptionally mediated and involves elements located in the 3′-untranslated region. Journal of Biological Chemistry 271, 17081–17090.Google Scholar
Chen, B., Zhong, D. and Monteiro, A. (2006). Comparative genomics and evolution of the HSP90 family of genes across all kingdoms of organisms. BioMed Central Genomics 7, 156. doi: 10.1186/1471-2164-7-156.Google Scholar
Chrobak, M., Forster, S., Meisel, S., Pfefferkorn, R., Forster, F. and Clos, J. (2012). Leishmania donovani HslV does not interact stably with HslU proteins. International Journal for Parasitology 42, 329–339. doi: 10.1016/j.ijpara.2012.01.008.Google Scholar
Clayton, C. E. (2002). Life without transcriptional control? From fly to man and back again. EMBO Journal 21, 1881–1888.Google Scholar
Clos, J. and Krobitsch, S. (1999). Heat shock as a regular feature of the life cycle of Leishmania parasites. American Zoologist 39, 848–856.CrossRefGoogle Scholar
Clos, J. and Choudhury, K. (2006). Functional cloning as a means to identify Leishmania genes involved in drug resistance. Mini Reviews in Medicinal Chemistry 6, 123–129.Google Scholar
Cruz, A., Coburn, C. M. and Beverley, S. M. (1991). Double targeted gene replacement for creating null mutants. Proceedings of the National Academy of Sciences USA 88, 7170–7174.Google Scholar
Dai, B., Wang, Y., Li, D., Xu, Y., Liang, R., Zhao, L., Cao, Y., Jia, J. and Jiang, Y. (2012). Hsp90 is involved in apoptosis of Candida albicans by regulating the calcineurin-caspase apoptotic pathway. PloS One 7, e45109. doi: 10.1371/journal.pone.0045109.Google Scholar
de Andrade, C. R., Kirchhoff, L. V., Donelson, J. E. and Otsu, K. (1992). Recombinant Leishmania Hsp90 and Hsp70 are recognized by sera from visceral leishmaniasis patients but not Chagas’ disease patients. Journal of Clinical Microbiology 30, 330–335.Google Scholar
Echeverria, P. C., Matrajt, M., Harb, O. S., Zappia, M. P., Costas, M. A., Roos, D. S., Dubremetz, J. F. and Angel, S. O. (2005). Toxoplasma gondii Hsp90 is a potential drug target whose expression and subcellular localization are developmentally regulated. Journal of Molecular Biology 350, 723–734. doi: 10.1016/j.jmb.2005.05.031.Google Scholar
Folgueira, C. and Requena, J. M. (2007). A postgenomic view of the heat shock proteins in kinetoplastids. FEMS Microbiology Reviews 31, 359–377. doi: 10.1111/j.1574-6976.2007.00069.x.Google Scholar
Forafonov, F., Toogun, O. A., Grad, I., Suslova, E., Freeman, B. C. and Picard, D. (2008). p23/Sba1p protects against Hsp90 inhibitors independently of its intrinsic chaperone activity. Molecular and Cellular Biology 28, 3446–3456. doi: 10.1128/MCB.02246-07.CrossRefGoogle ScholarPubMed
Garcia-Ranea, J. A., Mirey, G., Camonis, J. and Valencia, A. (2002). p23 and HSP20/alpha-crystallin proteins define a conserved sequence domain present in other eukaryotic protein families. FEBS Letters 529, 162–167.Google Scholar
Gartner, E. M., Silverman, P., Simon, M., Flaherty, L., Abrams, J., Ivy, P. and Lorusso, P. M. (2012). A phase II study of 17-allylamino-17-demethoxygeldanamycin in metastatic or locally advanced, unresectable breast cancer. Breast Cancer Research and Treatment 131, 933–937. doi: 10.1007/s10549-011-1866-7.Google Scholar
Genest, P. A., ter Riet, B., Dumas, C., Papadopoulou, B., van Luenen, H. G. and Borst, P. (2005). Formation of linear inverted repeat amplicons following targeting of an essential gene in Leishmania. Nucleic Acids Research 33, 1699–1709. doi: 10.1093/nar/gki304.Google Scholar
Graefe, S. E., Wiesgigl, M., Gaworski, I., Macdonald, A. and Clos, J. (2002). Inhibition of HSP90 in Trypanosoma cruzi induces a stress response but no stage differentiation. Eukaryotic Cell 1, 936–943.Google Scholar
Hassani, K., Antoniak, E., Jardim, A. and Olivier, M. (2011). Temperature-induced protein secretion by Leishmania mexicana modulates macrophage signalling and function. PloS One 6, e18724. doi: 10.1371/journal.pone.0018724.Google Scholar
Hombach, A. (2013). Mutational analysis of heat shock protein 90 from Leishmania donovani. Thesis, Faculty of Mathematics, Informatics and Science, University of Hamburg, Hamburg. http://ediss.sub.uni-hamburg.de/volltexte/2013/6492/.Google Scholar
Hombach, A., Ommen, G., Chrobak, M. and Clos, J. (2012). The Hsp90-Sti1 interaction is critical for Leishmania donovani proliferation in both life cycle stages. Cellular Microbiology 15, 585–600. doi: 10.1111/cmi.12057.Google Scholar
Hübel, A. and Clos, J. (1996). The genomic organization of the HSP83 gene locus is conserved in three Leishmania species. Experimental Parasitology 82, 225–228.Google Scholar
Hübel, A., Brandau, S., Dresel, A. and Clos, J. (1995). A member of the ClpB family of stress proteins is expressed during heat shock in Leishmania spp. Molecular and Biochemical Parasitology 70, 107–118.Google Scholar
Hübel, A., Krobitsch, S., Horauf, A. and Clos, J. (1997). Leishmania major Hsp100 is required chiefly in the mammalian stage of the parasite. Molecular and Cellular Biology 17, 5987–5995.CrossRefGoogle ScholarPubMed
Hunter, K. W., Cook, C. L. and Hayunga, E. G. (1984). Leishmanial differentiation in vitro: induction of heat shock proteins. Biochemical and Biophysical Research Communications 125, 755–760.Google Scholar
Ivens, A. C., Peacock, C. S., Worthey, E. A., Murphy, L., Aggarwal, G., Berriman, M., Sisk, E., Rajandream, M. A., Adlem, E., Aert, R., Anupama, A., Apostolou, Z., Attipoe, P., Bason, N., Bauser, C., Beck, A., Beverley, S. M., Bianchettin, G., Borzym, K., Bothe, G., Bruschi, C. V., Collins, M., Cadag, E., Ciarloni, L., Clayton, C., Coulson, R. M., Cronin, A., Cruz, A. K., Davies, R. M., De Gaudenzi, J., Dobson, D. E., Duesterhoeft, A., Fazelina, G., Fosker, N., Frasch, A. C., Fraser, A., Fuchs, M., Gabel, C., Goble, A., Goffeau, A., Harris, D., Hertz-Fowler, C., Hilbert, H., Horn, D., Huang, Y., Klages, S., Knights, A., Kube, M., Larke, N., Litvin, L., Lord, A., Louie, T., Marra, M., Masuy, D., Matthews, K., Michaeli, S., Mottram, J. C., Muller-Auer, S., Munden, H., Nelson, S., Norbertczak, H., Oliver, K., O'Neil, S., Pentony, M., Pohl, T. M., Price, C., Purnelle, B., Quail, M. A., Rabbinowitsch, E., Reinhardt, R., Rieger, M., Rinta, J., Robben, J., Robertson, L., Ruiz, J. C., Rutter, S., Saunders, D., Schafer, M., Schein, J., Schwartz, D. C., Seeger, K., Seyler, A., Sharp, S., Shin, H., Sivam, D., Squares, R., Squares, S., Tosato, V., Vogt, C., Volckaert, G., Wambutt, R., Warren, T., Wedler, H., Woodward, J., Zhou, S., Zimmermann, W., Smith, D. F., Blackwell, J. M., Stuart, K. D., Barrell, B. and Myler, P. J. (2005). The genome of the kinetoplastid parasite, Leishmania major . Science 309, 436–442.Google Scholar
Johnson, J. L. and Brown, C. (2009). Plasticity of the Hsp90 chaperone machine in divergent eukaryotic organisms. Cell Stress and Chaperones 14, 83–94.Google Scholar
Kim, Y. E., Hipp, M. S., Bracher, A., Hayer-Hartl, M. and Hartl, F. U. (2013). Molecular chaperone functions in protein folding and proteostasis. Annual Review of Biochemistry 82, 323–355. doi: 10.1146/annurev-biochem-060208-092442.CrossRefGoogle ScholarPubMed
Kitson, R. R. and Moody, C. J. (2013). Learning from nature: advances in geldanamycin- and radicicol-based inhibitors of Hsp90. Journal of Organic Chemistry 78, 5117–5141. doi: 10.1021/jo4002849.Google Scholar
Krobitsch, S. and Clos, J. (1999). A novel role for 100 kD heat shock proteins in the parasite Leishmania donovani . Cell Stress and Chaperones 4, 191–198.Google Scholar
Krobitsch, S., Brandau, S., Hoyer, C., Schmetz, C., Hübel, A. and Clos, J. (1998). Leishmania donovani heat shock protein 100: characterization and function in amastigote stage differentiation. Journal of Biological Chemistry 273, 6488–6494.Google Scholar
Kuhls, K., Alam, M. Z., Cupolillo, E., Ferreira, G. E., Mauricio, I. L., Oddone, R., Feliciangeli, M. D., Wirth, T., Miles, M. A. and Schonian, G. (2011). Comparative microsatellite typing of new world Leishmania infantum reveals low heterogeneity among populations and its recent old world origin. PLoS Neglected Tropical Diseases 5, e1155. doi: 10.1371/journal.pntd.0001155.Google Scholar
Lambertz, U., Silverman, J. M., Nandan, D., McMaster, W. R., Clos, J., Foster, L. J. and Reiner, N. E. (2012). Secreted virulence factors and immune evasion in visceral leishmaniasis. Journal of Leukocyte Biology 91, 887–899. doi: 10.1189/jlb.0611326.Google Scholar
Lawrence, F. and Robert-Gero, M. (1985). Induction of heat shock and stress proteins in promastigotes of three Leishmania species. Proceedings of the National Academy of Sciences USA 82, 4414–4417.Google Scholar
Lee, M. G., Atkinson, B. L., Giannini, S. H. and Van der Ploeg, L. H. (1988). Structure and expression of the hsp 70 gene family of Leishmania major [published erratum appears in Nucleic Acids Research 1988;16(23):11400–11401]. Nucleic Acids Research 16, 9567–9585.Google Scholar
Lye, L. F., Owens, K., Shi, H., Murta, S. M., Vieira, A. C., Turco, S. J., Tschudi, C., Ullu, E. and Beverley, S. M. (2010). Retention and loss of RNA interference pathways in trypanosomatid protozoans. PLoS Pathogens 6, e1001161. doi: 10.1371/journal.ppat.1001161.Google Scholar
MacFarlane, J., Blaxter, M. L., Bishop, R. P., Miles, M. A. and Kelly, J. M. (1990). Identification and characterisation of a Leishmania donovani antigen belonging to the 70-kDa heat-shock protein family. European Journal of Biochemistry 190, 377–384.Google Scholar
Mauricio, I. L., Stothard, J. R. and Miles, M. A. (2000). The strange case of Leishmania chagasi . Parasitology Today 16, 188–189.Google Scholar
Miller, J. (1988). Effects of temperature elevation on mRNA and protein synthesis in Leishmania mexicana amazonensis . Molecular and Biochemical Parasitology 30, 175–184.Google Scholar
Morales, M., Watanabe, R., Dacher, M., Chafey, P., Osorio y Fortéa, J., Beverley, S., Ommen, G., Clos, J., Hem, S., Lenormand, P., Rousselle, J.-C., Namane, A. and Spath, G. (2010). Phosphoproteome dynamics reveals heat shock protein complexes specific to the Leishmania infectious stage. Proceedings of the National Academy of Sciences USA 107, 8381–8386.Google Scholar
Myler, P. J., Sisk, E., McDonagh, P. D., Martinez-Calvillo, S., Schnaufer, A., Sunkin, S. M., Yan, S., Madhubala, R., Ivens, A. and Stuart, K. (2000). Genomic organization and gene function in Leishmania . Biochemical Society Transactions 28, 527–531.Google Scholar
Nathan, D. F. and Lindquist, S. (1995). Mutational analysis of Hsp90 function: interactions with a steroid receptor and a protein kinase. Molecular and Cellular Biology 15, 3917–3925.Google Scholar
Ochel, H. J., Eichhorn, K. and Gademann, G. (2001). Geldanamycin: the prototype of a class of antitumor drugs targeting the heat shock protein 90 family of molecular chaperones. Cell Stress and Chaperones 6, 105–112.Google Scholar
Oki, Y., Copeland, A., Romaguera, J., Fayad, L., Fanale, M., Faria Sde, C., Medeiros, L. J., Ivy, P. and Younes, A. (2012). Clinical experience with the heat shock protein-90 inhibitor, tanespimycin, in patients with relapsed lymphoma. Leukemia and Lymphoma 53, 990–992. doi: 10.3109/10428194.2011.631236.Google Scholar
Ommen, G. (2009). Charakterisierung putativer Co-Chaperonen des Parasiten Leishmania donovani (Ross, 1903). Thesis, Faculty of Mathematics, Informatics and Science, University of Hamburg, Hamburg. http://ediss.sub.uni-hamburg.de/volltexte/2010/4507/.Google Scholar
Ommen, G., Lorenz, S. and Clos, J. (2009). One-step generation of double-allele gene replacement mutants in Leishmania donovani . International Journal for Parasitology 39, 541–546.Google Scholar
Ommen, G., Chrobak, M. and Clos, J. (2010). The co-chaperone SGT of Leishmania donovani is essential for the parasite's viability. Cell Stress and Chaperones 39, 541–546. doi: 10.1007/s12192-009-0160-7.Google Scholar
Pearl, L. H. and Prodromou, C. (2006). Structure and mechanism of the Hsp90 molecular chaperone machinery. Annual Review of Biochemistry 75, 271–294. doi: 10.1146/annurev.biochem.75.103004.142738.Google Scholar
Petersen, A. L., Guedes, C. E., Versoza, C. L., Lima, J. G., de Freitas, L. A., Borges, V. M. and Veras, P. S. (2012). 17-AAG kills intracellular Leishmania amazonensis while reducing inflammatory responses in infected macrophages. PloS One 7, e49496. doi: 10.1371/journal.pone.0049496.Google Scholar
Picard, D. (2002). Heat-shock protein 90, a chaperone for folding and regulation. Cellular and Molecular Life Sciences 59, 1640–1648.Google Scholar
Pimenta, P. F. P., Turco, S. J., McConville, M. J., Lawyer, P. G., Perkins, P. V. and Sacks, D. L. (1992). Stage-specific adhesion of Leishmania promastigotes to the sandfly midgut. Science 256, 1812–1815.Google Scholar
Pratt, W. B. and Toft, D. O. (2003). Regulation of signaling protein function and trafficking by the hsp90/hsp70-based chaperone machinery. Experimental Biology and Medicine 228, 111–133.Google Scholar
Prodromou, C., Nuttall, J. M., Millson, S. H., Roe, S. M., Sim, T. S., Tan, D., Workman, P., Pearl, L. H. and Piper, P. W. (2009). Structural basis of the radicicol resistance displayed by a fungal Hsp90. ACS Chemical Biology 4, 289–297. doi: 10.1021/cb9000316.Google Scholar
Retzlaff, M., Stahl, M., Eberl, H. C., Lagleder, S., Beck, J., Kessler, H. and Buchner, J. (2009). Hsp90 is regulated by a switch point in the C-terminal domain. EMBO Reports 10, 1147–1153. doi: embor2009153 [pii] 10.1038/embor.2009.153.CrossRefGoogle ScholarPubMed
Rosenzweig, D., Smith, D., Opperdoes, F., Stern, S., Olafson, R. W. and Zilberstein, D. (2008). Retooling Leishmania metabolism: from sand fly gut to human macrophage. FASEB Journal 22, 590–602. doi: fj.07-9254com [pii] 10.1096/fj.07-9254com.Google Scholar
Rutherford, S. L. and Zuker, C. S. (1994). Protein folding and the regulation of signaling pathways. Cell 79, 1129–1132.Google Scholar
Sacks, D. L. (1989). Metacyclogenesis in Leishmania promastigotes. Experimental Parasitology 69, 100–103.CrossRefGoogle ScholarPubMed
Sacks, D. L. and Perkins, P. V. (1984). Identification of an infective stage of Leishmania promastigotes. Science 223, 1417–1419.Google Scholar
Sanchez, E. R., Meshinchi, S., Tienrungroj, W., Schlesinger, M. J., Toft, D. O. and Pratt, W. B. (1987). Relationship of the 90-kDa murine heat shock protein to the untransformed and transformed states of the L cell glucocorticoid receptor. Journal of Biological Chemistry 262, 6986–6991.Google Scholar
Schulte, T. W., Akinaga, S., Soga, S., Sullivan, W., Stensgard, B., Toft, D. and Neckers, L. M. (1998). Antibiotic radicicol binds to the N-terminal domain of Hsp90 and shares important biologic activities with geldanamycin. Cell Stress and Chaperones 3, 100–108.Google Scholar
Scroggins, B. T., Robzyk, K., Wang, D., Marcu, M. G., Tsutsumi, S., Beebe, K., Cotter, R. J., Felts, S., Toft, D., Karnitz, L., Rosen, N. and Neckers, L. (2007). An acetylation site in the middle domain of Hsp90 regulates chaperone function. Molecular Cell 25, 151–159. doi: 10.1016/j.molcel.2006.12.008.Google Scholar
Shapiro, R. S., Zaas, A. K., Betancourt-Quiroz, M., Perfect, J. R. and Cowen, L. E. (2012). The Hsp90 co-chaperone Sgt1 governs Candida albicans morphogenesis and drug resistance. PloS One 7, e44734. doi: 10.1371/journal.pone.0044734.Google Scholar
Sharma, S. V., Agatsuma, T. and Nakano, H. (1998). Targeting of the protein chaperone, HSP90, by the transformation suppressing agent, radicicol. Oncogene 16, 2639–2645.Google Scholar
Silverman, J. M., Clos, J., de'Oliveira, C. C., Shirvani, O., Fang, Y., Wang, C., Foster, L. J. and Reiner, N. E. (2010 a). An exosome-based secretion pathway is responsible for protein export from Leishmania and communication with macrophages. Journal of Cell Science 123, 842–852. doi: jcs.056465 [pii] 10.1242/jcs.056465.Google Scholar
Silverman, J. M., Clos, J., Horakova, E., Wang, A. Y., Wiesgigl, M., Kelly, I., Lynn, M. A., McMaster, W. R., Foster, L. J., Levings, M. K. and Reiner, N. E. (2010 b). Leishmania exosomes modulate innate and adaptive immune responses through effects on monocytes and dendritic cells. Journal of Immunology 185, 5011–5022.Google Scholar
Skeiky, Y. A., Benson, D. R., Guderian, J. A., Whittle, J. A., Bacelar, O., Carvalho, E. M. and Reed, S. G. (1995). Immune responses of leishmaniasis patients to heat shock proteins of Leishmania species and humans. Infection and Immunity 63, 4105–4114.Google Scholar
Skeiky, Y. A., Benson, D. R., Costa, J. L., Badaro, R. and Reed, S. G. (1997). Association of Leishmania heat shock protein 83 antigen and immunoglobulin G4 antibody titers in Brazilian patients with diffuse cutaneous leishmaniasis [In Process Citation]. Infection and Immunity 65, 5368–5370.Google Scholar
Smith, D. F., Whitesell, L. and Katsanis, E. (1998). Molecular chaperones: biology and prospects for pharmacological intervention. Pharmacological Reviews 50, 493–514.Google Scholar
The Myeloma Beacon (2010). Bristol-Myers Squibb halts development of Tanespimycin. In The Myeloma Beacon, Vol. 2014. (ed. Simkovich, B.), Light Knowledge Resources LLC, Princeton, NJ, USA Google Scholar
van der Ploeg, L. H. T., Giannini, S. H. and Cantor, C. R. (1985). Heat shock genes: regulatory role for differentiation in parasitic protozoa. Science 228, 1443–1446.Google Scholar
Vergnes, B., Gourbal, B., Girard, I., Sundar, S., Drummelsmith, J. and Ouellette, M. (2007). A proteomics screen implicates HSP83 and a small kinetoplastid calpain-related protein in drug resistance in Leishmania donovani clinical field isolates by modulating drug-induced programmed cell death. Molecular and Cellular Proteomics 6, 88–101. doi: 10.1074/mcp.M600319-MCP200.CrossRefGoogle Scholar
Webb, J. R., Campos-Neto, A., Skeiky, Y. A. and Reed, S. G. (1997). Molecular characterization of the heat-inducible LmSTI1 protein of Leishmania major [In Process Citation]. Molecular and Biochemical Parasitology 89, 179–193.Google Scholar
Wenzel, U. A., Bank, E., Florian, C., Forster, S., Zimara, N., Steinacker, J., Klinger, M., Reiling, N., Ritter, U. and van Zandbergen, G. (2012). Leishmania major parasite stage-dependent host cell invasion and immune evasion. FASEB Journal 26, 29–39. doi: 10.1096/fj.11-184895.Google Scholar
Whitesell, L. and Cook, P. (1996). Stable and specific binding of heat shock protein 90 by geldanamycin disrupts glucocorticoid receptor function in intact cells. Molecular Endocrinology 10, 705–712.Google Scholar
Whitesell, L. and Lindquist, S. L. (2005). Hsp90 and the chaperoning of cancer. Nature Reviews Cancer 5, 761–772.CrossRefGoogle ScholarPubMed
Whitesell, L., Mimnaugh, E. G., De Costa, B., Myers, C. E. and Neckers, L. M. (1994). Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation. Proceedings of the National Academy of Sciences USA 91, 8324–8328.Google Scholar
Wiesgigl, M. and Clos, J. (2001). Heat shock protein 90 homeostasis controls stage differentiation in Leishmania donovani . Molecular Biology of the Cell 12, 3307–3316.Google Scholar
Wilson, M. E., Andersen, K. A. and Britigan, B. E. (1994). Response of Leishmania chagasi promastigotes to oxidant stress. Infection and Immunity 62, 5133–5141.Google Scholar
Workman, P., Burrows, F., Neckers, L. and Rosen, N. (2007). Drugging the cancer chaperone HSP90: combinatorial therapeutic exploitation of oncogene addiction and tumor stress. Annals of the New York Academy of Sciences 1113, 202–216.Google Scholar
Zhang, T., Hamza, A., Cao, X., Wang, B., Yu, S., Zhan, C. G. and Sun, D. (2008). A novel Hsp90 inhibitor to disrupt Hsp90/Cdc37 complex against pancreatic cancer cells. Molecular Cancer Therapeutics 7, 162–170. doi: 10.1158/1535-7163.MCT-07-0484.Google Scholar
Zilberstein, D. and Shapira, M. (1994). The role of pH and temperature in the development of Leishmania parasites. Annual Review of Microbiology 48, 449–470.Google Scholar
Zilka, A., Garlapati, S., Dahan, E., Yaolsky, V. and Shapira, M. (2001). Developmental regulation of HSP83 in Leishmania: transcript levels are controlled by the efficiency of 3? RNA processing and preferential translation is directed by a determinant in the 3′ UTR. Journal of Biological Chemistry 11, 11.Google Scholar