Skip to main content
×
Home
    • Aa
    • Aa

No stress – Hsp90 and signal transduction in Leishmania

  • A. HOMBACH (a1) and J. CLOS (a1)
Summary
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.

Copyright
Corresponding author
* Corresponding author: Bernhard Nocht Institute for Tropical Medicine, Bernhard Nocht St 74, 20359 Hamburg, Germany. E-mail: clos@bnitm.de
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

A. Alexandratos , J. Clos , M. Samiotaki , A. Efstathiou , G. Panayotou , K. Soteriadou and D. Smirlis (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, 10151031. doi: 10.1111/mmi.12240.

J. Alvar , I. D. Velez , C. Bern , M. Herrero , P. Desjeux , J. Cano , J. Jannin and M. den Boer (2012). Leishmaniasis worldwide and global estimates of its incidence. PloS One 7, e35671. doi: 10.1371/journal.pone.0035671.

M. Argaman , R. Aly and M. Shapira (1994). Expression of heat shock protein 83 in Leishmania is regulated post-transcriptionally. Molecular and Biochemical Parasitology 64, 95110.

G. Banumathy , V. Singh , S. R. Pavithra and U. Tatu (2003). Heat shock protein 90 function is essential for Plasmodium falciparum growth in human erythrocytes. Journal of Biological Chemistry 278, 1833618345. doi: 10.1074/jbc.M211309200.

E. Barak , S. Amin-Spector , E. Gerliak , S. Goyard , N. Holland and D. Zilberstein (2005). Differentiation of Leishmania donovani in host-free system: analysis of signal perception and response. Molecular and Biochemical Parasitology 141, 99108.

P. A. Bates (1993). Axenic amastigote culture of Leishmania amastigotes. Parasitology Today 9, 143146.

M. Bente , S. Harder , M. Wiesgigl , J. Heukeshoven , C. Gelhaus , E. Krause , J. Clos and I. Bruchhaus (2003). Developmentally induced changes of the proteome in the protozoan parasite Leishmania donovani. Proteomics 3, 18111829.

S. Brandau , A. Dresel and J. Clos (1995). High constitutive levels of heat-shock proteins in human-pathogenic parasites of the genus Leishmania. Biochemical Journal 310, 225232.

C. Brochu , A. Haimeur and M. Ouellette (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, 294303.

J. Buchner (1999). Hsp90 & Co. – a holding for folding. Trends in Biochemical Sciences 24, 136141.

H. Charest and G. Matlashewski (1994). Developmental gene expression in Leishmania donovani: differential cloning and analysis of an amastigote-stage-specific gene. Molecular and Cellular Biology 14, 29752984.

H. Charest , W.-W. Zhang and G. Matlashewski (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, 1708117090.

M. Chrobak , S. Forster , S. Meisel , R. Pfefferkorn , F. Forster and J. Clos (2012). Leishmania donovani HslV does not interact stably with HslU proteins. International Journal for Parasitology 42, 329339. doi: 10.1016/j.ijpara.2012.01.008.

C. E. Clayton (2002). Life without transcriptional control? From fly to man and back again. EMBO Journal 21, 18811888.

J. Clos and S. Krobitsch (1999). Heat shock as a regular feature of the life cycle of Leishmania parasites. American Zoologist 39, 848856.

J. Clos and K. Choudhury (2006). Functional cloning as a means to identify Leishmania genes involved in drug resistance. Mini Reviews in Medicinal Chemistry 6, 123129.

A. Cruz , C. M. Coburn and S. M. Beverley (1991). Double targeted gene replacement for creating null mutants. Proceedings of the National Academy of Sciences USA 88, 71707174.

B. Dai , Y. Wang , D. Li , Y. Xu , R. Liang , L. Zhao , Y. Cao , J. Jia and Y. Jiang (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.

P. C. Echeverria , M. Matrajt , O. S. Harb , M. P. Zappia , M. A. Costas , D. S. Roos , J. F. Dubremetz and S. O. Angel (2005). Toxoplasma gondii Hsp90 is a potential drug target whose expression and subcellular localization are developmentally regulated. Journal of Molecular Biology 350, 723734. doi: 10.1016/j.jmb.2005.05.031.

C. Folgueira and J. M. Requena (2007). A postgenomic view of the heat shock proteins in kinetoplastids. FEMS Microbiology Reviews 31, 359377. doi: 10.1111/j.1574-6976.2007.00069.x.

F. Forafonov , O. A. Toogun , I. Grad , E. Suslova , B. C. Freeman and D. Picard (2008). p23/Sba1p protects against Hsp90 inhibitors independently of its intrinsic chaperone activity. Molecular and Cellular Biology 28, 34463456. doi: 10.1128/MCB.02246-07.

J. A. Garcia-Ranea , G. Mirey , J. Camonis and A. Valencia (2002). p23 and HSP20/alpha-crystallin proteins define a conserved sequence domain present in other eukaryotic protein families. FEBS Letters 529, 162167.

E. M. Gartner , P. Silverman , M. Simon , L. Flaherty , J. Abrams , P. Ivy and P. M. Lorusso (2012). A phase II study of 17-allylamino-17-demethoxygeldanamycin in metastatic or locally advanced, unresectable breast cancer. Breast Cancer Research and Treatment 131, 933937. doi: 10.1007/s10549-011-1866-7.

P. A. Genest , B. ter Riet , C. Dumas , B. Papadopoulou , H. G. van Luenen and P. Borst (2005). Formation of linear inverted repeat amplicons following targeting of an essential gene in Leishmania. Nucleic Acids Research 33, 16991709. doi: 10.1093/nar/gki304.

S. E. Graefe , M. Wiesgigl , I. Gaworski , A. Macdonald and J. Clos (2002). Inhibition of HSP90 in Trypanosoma cruzi induces a stress response but no stage differentiation. Eukaryotic Cell 1, 936943.

K. Hassani , E. Antoniak , A. Jardim and M. Olivier (2011). Temperature-induced protein secretion by Leishmania mexicana modulates macrophage signalling and function. PloS One 6, e18724. doi: 10.1371/journal.pone.0018724.

A. Hombach , G. Ommen , M. Chrobak and J. Clos (2012). The Hsp90-Sti1 interaction is critical for Leishmania donovani proliferation in both life cycle stages. Cellular Microbiology 15, 585600. doi: 10.1111/cmi.12057.

A. Hübel and J. Clos (1996). The genomic organization of the HSP83 gene locus is conserved in three Leishmania species. Experimental Parasitology 82, 225228.

A. Hübel , S. Brandau , A. Dresel and J. Clos (1995). A member of the ClpB family of stress proteins is expressed during heat shock in Leishmania spp. Molecular and Biochemical Parasitology 70, 107118.

A. Hübel , S. Krobitsch , A. Horauf and J. Clos (1997). Leishmania major Hsp100 is required chiefly in the mammalian stage of the parasite. Molecular and Cellular Biology 17, 59875995.

K. W. Hunter , C. L. Cook and E. G. Hayunga (1984). Leishmanial differentiation in vitro: induction of heat shock proteins. Biochemical and Biophysical Research Communications 125, 755760.

A. C. Ivens , C. S. Peacock , E. A. Worthey , L. Murphy , G. Aggarwal , M. Berriman , E. Sisk , M. A. Rajandream , E. Adlem , R. Aert , A. Anupama , Z. Apostolou , P. Attipoe , N. Bason , C. Bauser , A. Beck , S. M. Beverley , G. Bianchettin , K. Borzym , G. Bothe , C. V. Bruschi , M. Collins , E. Cadag , L. Ciarloni , C. Clayton , R. M. Coulson , A. Cronin , A. K. Cruz , R. M. Davies , J. De Gaudenzi , D. E. Dobson , A. Duesterhoeft , G. Fazelina , N. Fosker , A. C. Frasch , A. Fraser , M. Fuchs , C. Gabel , A. Goble , A. Goffeau , D. Harris , C. Hertz-Fowler , H. Hilbert , D. Horn , Y. Huang , S. Klages , A. Knights , M. Kube , N. Larke , L. Litvin , A. Lord , T. Louie , M. Marra , D. Masuy , K. Matthews , S. Michaeli , J. C. Mottram , S. Muller-Auer , H. Munden , S. Nelson , H. Norbertczak , K. Oliver , S. O'Neil , M. Pentony , T. M. Pohl , C. Price , B. Purnelle , M. A. Quail , E. Rabbinowitsch , R. Reinhardt , M. Rieger , J. Rinta , J. Robben , L. Robertson , J. C. Ruiz , S. Rutter , D. Saunders , M. Schafer , J. Schein , D. C. Schwartz , K. Seeger , A. Seyler , S. Sharp , H. Shin , D. Sivam , R. Squares , S. Squares , V. Tosato , C. Vogt , G. Volckaert , R. Wambutt , T. Warren , H. Wedler , J. Woodward , S. Zhou , W. Zimmermann , D. F. Smith , J. M. Blackwell , K. D. Stuart , B. Barrell and P. J. Myler (2005). The genome of the kinetoplastid parasite, Leishmania major. Science 309, 436442.

J. L. Johnson and C. Brown (2009). Plasticity of the Hsp90 chaperone machine in divergent eukaryotic organisms. Cell Stress and Chaperones 14, 8394.

Y. E. Kim , M. S. Hipp , A. Bracher , M. Hayer-Hartl and F. U. Hartl (2013). Molecular chaperone functions in protein folding and proteostasis. Annual Review of Biochemistry 82, 323355. doi: 10.1146/annurev-biochem-060208-092442.

R. R. Kitson and C. J. Moody (2013). Learning from nature: advances in geldanamycin- and radicicol-based inhibitors of Hsp90. Journal of Organic Chemistry 78, 51175141. doi: 10.1021/jo4002849.

S. Krobitsch and J. Clos (1999). A novel role for 100 kD heat shock proteins in the parasite Leishmania donovani. Cell Stress and Chaperones 4, 191198.

S. Krobitsch , S. Brandau , C. Hoyer , C. Schmetz , A. Hübel and J. Clos (1998). Leishmania donovani heat shock protein 100: characterization and function in amastigote stage differentiation. Journal of Biological Chemistry 273, 64886494.

K. Kuhls , M. Z. Alam , E. Cupolillo , G. E. Ferreira , I. L. Mauricio , R. Oddone , M. D. Feliciangeli , T. Wirth , M. A. Miles and G. Schonian (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.

U. Lambertz , J. M. Silverman , D. Nandan , W. R. McMaster , J. Clos , L. J. Foster and N. E. Reiner (2012). Secreted virulence factors and immune evasion in visceral leishmaniasis. Journal of Leukocyte Biology 91, 887899. doi: 10.1189/jlb.0611326.

F. Lawrence and M. Robert-Gero (1985). Induction of heat shock and stress proteins in promastigotes of three Leishmania species. Proceedings of the National Academy of Sciences USA 82, 44144417.

M. G. Lee , B. L. Atkinson , S. H. Giannini and L. H. Van der Ploeg (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, 95679585.

L. F. Lye , K. Owens , H. Shi , S. M. Murta , A. C. Vieira , S. J. Turco , C. Tschudi , E. Ullu and S. M. Beverley (2010). Retention and loss of RNA interference pathways in trypanosomatid protozoans. PLoS Pathogens 6, e1001161. doi: 10.1371/journal.ppat.1001161.

J. MacFarlane , M. L. Blaxter , R. P. Bishop , M. A. Miles and J. M. Kelly (1990). Identification and characterisation of a Leishmania donovani antigen belonging to the 70-kDa heat-shock protein family. European Journal of Biochemistry 190, 377384.

I. L. Mauricio , J. R. Stothard and M. A. Miles (2000). The strange case of Leishmania chagasi. Parasitology Today 16, 188189.

J. Miller (1988). Effects of temperature elevation on mRNA and protein synthesis in Leishmania mexicana amazonensis. Molecular and Biochemical Parasitology 30, 175184.

M. Morales , R. Watanabe , M. Dacher , P. Chafey , J. Osorio y Fortéa , S. Beverley , G. Ommen , J. Clos , S. Hem , P. Lenormand , J.-C. Rousselle , A. Namane and G. Spath (2010). Phosphoproteome dynamics reveals heat shock protein complexes specific to the Leishmania infectious stage. Proceedings of the National Academy of Sciences USA 107, 83818386.

P. J. Myler , E. Sisk , P. D. McDonagh , S. Martinez-Calvillo , A. Schnaufer , S. M. Sunkin , S. Yan , R. Madhubala , A. Ivens and K. Stuart (2000). Genomic organization and gene function in Leishmania. Biochemical Society Transactions 28, 527531.

D. F. Nathan and S. Lindquist (1995). Mutational analysis of Hsp90 function: interactions with a steroid receptor and a protein kinase. Molecular and Cellular Biology 15, 39173925.

H. J. Ochel , K. Eichhorn and G. Gademann (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, 105112.

Y. Oki , A. Copeland , J. Romaguera , L. Fayad , M. Fanale , C. Faria Sde , L. J. Medeiros , P. Ivy and A. Younes (2012). Clinical experience with the heat shock protein-90 inhibitor, tanespimycin, in patients with relapsed lymphoma. Leukemia and Lymphoma 53, 990992. doi: 10.3109/10428194.2011.631236.

G. Ommen , S. Lorenz and J. Clos (2009). One-step generation of double-allele gene replacement mutants in Leishmania donovani. International Journal for Parasitology 39, 541546.

L. H. Pearl and C. Prodromou (2006). Structure and mechanism of the Hsp90 molecular chaperone machinery. Annual Review of Biochemistry 75, 271294. doi: 10.1146/annurev.biochem.75.103004.142738.

A. L. Petersen , C. E. Guedes , C. L. Versoza , J. G. Lima , L. A. de Freitas , V. M. Borges and P. S. Veras (2012). 17-AAG kills intracellular Leishmania amazonensis while reducing inflammatory responses in infected macrophages. PloS One 7, e49496. doi: 10.1371/journal.pone.0049496.

D. Picard (2002). Heat-shock protein 90, a chaperone for folding and regulation. Cellular and Molecular Life Sciences 59, 16401648.

P. F. P. Pimenta , S. J. Turco , M. J. McConville , P. G. Lawyer , P. V. Perkins and D. L. Sacks (1992). Stage-specific adhesion of Leishmania promastigotes to the sandfly midgut. Science 256, 18121815.

C. Prodromou , J. M. Nuttall , S. H. Millson , S. M. Roe , T. S. Sim , D. Tan , P. Workman , L. H. Pearl and P. W. Piper (2009). Structural basis of the radicicol resistance displayed by a fungal Hsp90. ACS Chemical Biology 4, 289297. doi: 10.1021/cb9000316.

M. Retzlaff , M. Stahl , H. C. Eberl , S. Lagleder , J. Beck , H. Kessler and J. Buchner (2009). Hsp90 is regulated by a switch point in the C-terminal domain. EMBO Reports 10, 11471153. doi: embor2009153 [pii] 10.1038/embor.2009.153.

D. Rosenzweig , D. Smith , F. Opperdoes , S. Stern , R. W. Olafson and D. Zilberstein (2008). Retooling Leishmania metabolism: from sand fly gut to human macrophage. FASEB Journal 22, 590602. doi: fj.07-9254com [pii] 10.1096/fj.07-9254com.

S. L. Rutherford and C. S. Zuker (1994). Protein folding and the regulation of signaling pathways. Cell 79, 11291132.

D. L. Sacks (1989). Metacyclogenesis in Leishmania promastigotes. Experimental Parasitology 69, 100103.

D. L. Sacks and P. V. Perkins (1984). Identification of an infective stage of Leishmania promastigotes. Science 223, 14171419.

T. W. Schulte , S. Akinaga , S. Soga , W. Sullivan , B. Stensgard , D. Toft and L. M. Neckers (1998). Antibiotic radicicol binds to the N-terminal domain of Hsp90 and shares important biologic activities with geldanamycin. Cell Stress and Chaperones 3, 100108.

B. T. Scroggins , K. Robzyk , D. Wang , M. G. Marcu , S. Tsutsumi , K. Beebe , R. J. Cotter , S. Felts , D. Toft , L. Karnitz , N. Rosen and L. Neckers (2007). An acetylation site in the middle domain of Hsp90 regulates chaperone function. Molecular Cell 25, 151159. doi: 10.1016/j.molcel.2006.12.008.

R. S. Shapiro , A. K. Zaas , M. Betancourt-Quiroz , J. R. Perfect and L. E. Cowen (2012). The Hsp90 co-chaperone Sgt1 governs Candida albicans morphogenesis and drug resistance. PloS One 7, e44734. doi: 10.1371/journal.pone.0044734.

S. V. Sharma , T. Agatsuma and H. Nakano (1998). Targeting of the protein chaperone, HSP90, by the transformation suppressing agent, radicicol. Oncogene 16, 26392645.

J. M. Silverman , J. Clos , C. C. de'Oliveira , O. Shirvani , Y. Fang , C. Wang , L. J. Foster and N. E. Reiner (2010 a). An exosome-based secretion pathway is responsible for protein export from Leishmania and communication with macrophages. Journal of Cell Science 123, 842852. doi: jcs.056465 [pii] 10.1242/jcs.056465.

J. M. Silverman , J. Clos , E. Horakova , A. Y. Wang , M. Wiesgigl , I. Kelly , M. A. Lynn , W. R. McMaster , L. J. Foster , M. K. Levings and N. E. Reiner (2010 b). Leishmania exosomes modulate innate and adaptive immune responses through effects on monocytes and dendritic cells. Journal of Immunology 185, 50115022.

L. H. T. van der Ploeg , S. H. Giannini and C. R. Cantor (1985). Heat shock genes: regulatory role for differentiation in parasitic protozoa. Science 228, 14431446.

B. Vergnes , B. Gourbal , I. Girard , S. Sundar , J. Drummelsmith and M. Ouellette (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, 88101. doi: 10.1074/mcp.M600319-MCP200.

J. R. Webb , A. Campos-Neto , Y. A. Skeiky and S. G. Reed (1997). Molecular characterization of the heat-inducible LmSTI1 protein of Leishmania major [In Process Citation]. Molecular and Biochemical Parasitology 89, 179193.

U. A. Wenzel , E. Bank , C. Florian , S. Forster , N. Zimara , J. Steinacker , M. Klinger , N. Reiling , U. Ritter and G. van Zandbergen (2012). Leishmania major parasite stage-dependent host cell invasion and immune evasion. FASEB Journal 26, 2939. doi: 10.1096/fj.11-184895.

L. Whitesell and P. Cook (1996). Stable and specific binding of heat shock protein 90 by geldanamycin disrupts glucocorticoid receptor function in intact cells. Molecular Endocrinology 10, 705712.

L. Whitesell and S. L. Lindquist (2005). Hsp90 and the chaperoning of cancer. Nature Reviews Cancer 5, 761772.

L. Whitesell , E. G. Mimnaugh , B. De Costa , C. E. Myers and L. M. Neckers (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, 83248328.

M. Wiesgigl and J. Clos (2001). Heat shock protein 90 homeostasis controls stage differentiation in Leishmania donovani. Molecular Biology of the Cell 12, 33073316.

P. Workman , F. Burrows , L. Neckers and N. Rosen (2007). Drugging the cancer chaperone HSP90: combinatorial therapeutic exploitation of oncogene addiction and tumor stress. Annals of the New York Academy of Sciences 1113, 202216.

T. Zhang , A. Hamza , X. Cao , B. Wang , S. Yu , C. G. Zhan and D. Sun (2008). A novel Hsp90 inhibitor to disrupt Hsp90/Cdc37 complex against pancreatic cancer cells. Molecular Cancer Therapeutics 7, 162170. doi: 10.1158/1535-7163.MCT-07-0484.

D. Zilberstein and M. Shapira (1994). The role of pH and temperature in the development of Leishmania parasites. Annual Review of Microbiology 48, 449470.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Parasitology
  • ISSN: 0031-1820
  • EISSN: 1469-8161
  • URL: /core/journals/parasitology
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords:

Metrics

Full text views

Total number of HTML views: 10
Total number of PDF views: 31 *
Loading metrics...

Abstract views

Total abstract views: 173 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 24th September 2017. This data will be updated every 24 hours.