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Toxoplasma gondii Hsp90: potential roles in essential cellular processes of the parasite

  • SERGIO O. ANGEL (a1), MARIA J. FIGUERAS (a1), MARIA L. ALOMAR (a1), PABLO C. ECHEVERRIA (a2) and BIN DENG (a3)...
Summary
SUMMARY

Hsp90 is a widely distributed and highly conserved molecular chaperone that is ubiquitously expressed throughout nature, being one of the most abundant proteins within non-stressed cells. This chaperone is up-regulated following stressful events and has been involved in many cellular processes. In Toxoplasma gondii, Hsp90 could be linked with many essential processes of the parasite such as host cell invasion, replication and tachyzoite-bradyzoite interconversion. A Protein-Protein Interaction (PPI) network approach of TgHsp90 has allowed inferring how these processes may be altered. In addition, data mining of T. gondii phosphoproteome and acetylome has allowed the generation of the phosphorylation and acetylation map of TgHsp90. This review focuses on the potential roles of TgHsp90 in parasite biology and the analysis of experimental data in comparison with its counterparts in yeast and humans.

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* Corresponding author. Laboratorio de Parasitología Molecular, IIB-INTECH, CONICET-UNSAM, Av. Intendente Marino Km. 8·2, C.C 164, (B7130IIWA), Chascomús, Prov. Buenos Aires, Argentina. E-mail: sangel@intech.gov.ar
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H. J. Ahn , S. Kim and W. Nam (2003). Molecular cloning of the 82-kDa heat shock protein (HSP90) of Toxoplasma gondii associated with the entry into and growth in host cells. Biochemical and Biophysical Research Communication 311, 654659.

S. O. Angel , M. Matrajt and P. C. Echeverria (2013). A review of recent patents on the protozoan parasite HSP90 as a drug target. Recent Patent on Biotechnology 7, 28.

M. Bedin , M. G. Catelli , L. Cabanie , A. M. Gaben and J. Mester (2009). Indirect participation of Hsp90 in the regulation of the cyclin E turnover. Biochemical Pharmacology 77, 151158.

M. S. Behnke , J. C. Wootton , M. M. Lehmann , J. B. Radke , O. Lucas , J. Nawas , L. D. Sibley and M. W. White (2010). Coordinated progression through two subtranscriptomes underlies the tachyzoite cycle of Toxoplasma gondii. PLoS One 5, e12354.

D. Bogumil and T. Dagan (2012). Cumulative impact of chaperone-mediated folding on genome evolution. Biochemistry 51, 99419953.

F. Burrows , H. Zhang and A. Kamal (2004). Hsp90 activation and cell cycle regulation. Cell Cycle 3, 15301536.

Y. Carlier , C. Truyens , P. Deloron and F. Peyron (2012). Congenital parasitic infections: a review. Acta Tropica 121, 5570.

V. Carruthers and J. C. Boothroyd (2007). Pulling together: an integrated model of Toxoplasma cell invasion. Current Opinion in Microbiology 10, 8389.

M. G. Catlett and K. B. Kaplan (2006). Sgt1p is a unique co-chaperone that acts as a client adaptor to link Hsp90 to Skp1p. Journal of Biological Chemistry 281, 3373933748.

M. M. Croken , S. C. Nardelli and K. Kim (2012). Chromatin modifications, epigenetics, and how protozoan parasites regulate their lives. Trends in Parasitology 28, 202213.

M. C. Dalmasso , W. J. Sullivan Jr. and S. O. Angel (2011). Canonical and variant histones of protozoan parasites. Frontiers in Bioscience (Landmark Ed) 16, 20862105.

F. Dzierszinski , M. Nishi , L. Ouko and D. S. Roos (2004). Dynamics of Toxoplasma gondii differentiation. Eukaryotic Cell 3, 9921003.

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.

P. C. Echeverria , M. J. Figueras , M. Vogler , T. Kriehuber , N. de Miguel , B. Deng , M. C. Dalmasso , D. E. Matthews , M. Matrajt , M. Haslbeck , J. Buchner and S. O. Angel (2010). The Hsp90 co-chaperone p23 of Toxoplasma gondii: identification, functional analysis and dynamic interactome determination. Molecular and Biochemical Parasitology 172, 129140.

P. C. Echeverria , A. Bernthaler , P. Dupuis , B. Mayer and D. Picard (2011). An interaction network predicted from public data as a discovery tool: application to the Hsp90 molecular chaperone machine. PLoS One 6, e26044.

M. J. Figueras , O. A. Martin , P. C. Echeverria , N. de Miguel , A. Naguleswaran , W. J. Sullivan Jr., M. M. Corvi and S. O. Angel (2012). Toxoplasma gondii Sis1-like J-domain protein is a cytosolic chaperone associated to HSP90/HSP70 complex. International Journal for Biological Macromolecules 50, 725733.

M. J. Gubbels , M. White and T. Szatanek (2008). The cell cycle and Toxoplasma gondii cell division: tightly knit or loosely stitched? International Journal of Parasitology 38, 13431358.

H. E. Haarberg , K. H. Paraiso , E. Wood , V. W. Rebecca , V. K. Sondak , J. M. Koomen and K. S. Smalley (2013). Inhibition of Wee1, AKT, and CDK4 underlies the efficacy of the HSP90 inhibitor XL888 in an in vivo model of NRAS-mutant melanoma. Molecular Cancer Therapeutics 12, 901912.

S. K. Halonen and L. M. Weiss (2013). Toxoplasmosis. Handbook of Clinical Neurology 114, 125145.

S. E. Jackson (2013). Hsp90: structure and function. Topics in Current Chemistry 328, 155240.

V. Jeffers and W. J. Sullivan Jr. (2012). Lysine acetylation is widespread on proteins of diverse function and localization in the protozoan parasite Toxoplasma gondii. Eukaryotic Cell 11, 735742.

C. Konrad , S. F. Queener , R. C. Wek and W. J. Sullivan Jr. (2013). Inhibitors of eIF2alpha dephosphorylation slow replication and stabilize latency in Toxoplasma gondii. Antimicrobial Agents and Chemotherapy 57, 18151822.

J. J. Kovacs , P. J. Murphy , S. Gaillard , X. Zhao , J. T. Wu , C. V. Nicchitta , M. Yoshida , D. O. Toft , W. B. Pratt and T. P. Yao (2005). HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor. Molecular Cell 18, 601607.

J. Li , J. Soroka and J. Buchner (2012). The Hsp90 chaperone machinery: conformational dynamics and regulation by co-chaperones. Biochimica et Biophysica Acta 1823, 624635.

U. Liwak and S. Ananvoranich (2009). Toxoplasma gondii: over-expression of lactate dehydrogenase enhances differentiation under alkaline conditions. Experimental Parasitology 122, 155161.

S. Lourido , K. Tang and L. D. Sibley (2012). Distinct signalling pathways control Toxoplasma egress and host-cell invasion. EMBO Journal 31, 45244534.

T. Makhnevych and W. A. Houry (2012). The role of Hsp90 in protein complex assembly. Biochimica et Biophysica Acta 1823, 674682.

A. Martinez-Ruiz , L. Villanueva , C. Gonzalez de Orduna , D. Lopez-Ferrer , M. A. Higueras , C. Tarin , I. Rodriguez-Crespo , J. Vazquez and S. Lamas (2005). S-nitrosylation of Hsp90 promotes the inhibition of its ATPase and endothelial nitric oxide synthase regulatory activities. Proceedings of the National Academy of Sciences USA 102, 85258530.

A. J. McClellan , Y. Xia , A. M. Deutschbauer , R. W. Davis , M. Gerstein and J. Frydman (2007). Diverse cellular functions of the Hsp90 molecular chaperone uncovered using systems approaches. Cell 131, 121135.

M. Meissner and D. Soldati (2005). The transcription machinery and the molecular toolbox to control gene expression in Toxoplasma gondii and other protozoan parasites. Microbes and Infection 7, 13761384.

O. Miman , E. A. Mutlu , O. Ozcan , M. Atambay , R. Karlidag and S. Unal (2010). Is there any role of Toxoplasma gondii in the etiology of obsessive-compulsive disorder? Psychiatry Research 177, 263265.

E. G. Mimnaugh , P. J. Worland , L. Whitesell and L. M. Neckers (1995). Possible role for serine/threonine phosphorylation in the regulation of the heteroprotein complex between the hsp90 stress protein and the pp60v-src tyrosine kinase. Journal of Biological Chemistry 270, 2865428659.

M. Mollapour and L. Neckers (2012). Post-translational modifications of Hsp90 and their contributions to chaperone regulation. Biochimica et Biophysica Acta 1823, 648655.

M. Mollapour , S. Tsutsumi , A. C. Donnelly , K. Beebe , M. J. Tokita , M. J. Lee , S. Lee , G. Morra , D. Bourboulia , B. T. Scroggins , G. Colombo , B. S. Blagg , B. Panaretou , W. G. Stetler-Stevenson , J. B. Trepel , P. W. Piper , C. Prodromou , L. H. Pearl and L. Neckers (2010 a). Swe1Wee1-dependent tyrosine phosphorylation of Hsp90 regulates distinct facets of chaperone function. Molecular Cell 37, 333343.

M. Mollapour , S. Tsutsumi and L. Neckers (2010 b). Hsp90 phosphorylation, Wee1 and the cell cycle. Cell Cycle 9, 23102316.

M. Mollapour , S. Tsutsumi , Y. S. Kim , J. Trepel and L. Neckers (2011 a). Casein kinase 2 phosphorylation of Hsp90 threonine 22 modulates chaperone function and drug sensitivity. Oncotarget 2, 407417.

M. Mollapour , S. Tsutsumi , A. W. Truman , W. Xu , C. K. Vaughan , K. Beebe , A. Konstantinova , S. Vourganti , B. Panaretou , P. W. Piper , J. B. Trepel , C. Prodromou , L. H. Pearl and L. Neckers (2011 b). Threonine 22 phosphorylation attenuates Hsp90 interaction with cochaperones and affects its chaperone activity. Molecular Cell 41, 672681.

P. J. Murphy , Y. Morishima , J. J. Kovacs , T. P. Yao and W. B. Pratt (2005). Regulation of the dynamics of hsp90 action on the glucocorticoid receptor by acetylation/deacetylation of the chaperone. Journal of Biological Chemistry 280, 3379233799.

J. Narasimhan , B. R. Joyce , A. Naguleswaran , A. T. Smith , M. R. Livingston , S. E. Dixon , I. Coppens , R. C. Wek and W. J. Sullivan Jr. (2008). Translation regulation by eukaryotic initiation factor-2 kinases in the development of latent cysts in Toxoplasma gondii. Journal of Biological Chemistry 283, 1659116601.

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

H. Ogiso , N. Kagi , E. Matsumoto , M. Nishimoto , R. Arai , M. Shirouzu , J. Mimura , Y. Fujii-Kuriyama and S. Yokoyama (2004). Phosphorylation analysis of 90 kDa heat shock protein within the cytosolic arylhydrocarbon receptor complex. Biochemistry 43, 1551015519.

J. H. Park , S. H. Kim , M. C. Choi , J. Lee , D. Y. Oh , S. A. Im , Y. J. Bang and T. Y. Kim (2008). Class II histone deacetylases play pivotal roles in heat shock protein 90-mediated proteasomal degradation of vascular endothelial growth factor receptors. Biochemical and Biophysical Research Communication 368, 318322.

M. H. Park , Y. J. Kwon , H. Y. Jeong , H. Y. Lee , Y. Hwangbo , H. J. Yoon and S. H. Shim (2012). Association between intracellular infectious agents and schizophrenia. Clinical Psychopharmacology and Neuroscience 10, 117123.

S. R. Pavithra , R. Kumar and U. Tatu (2007). Systems analysis of chaperone networks in the malarial parasite Plasmodium falciparum. PLOS Computational Biology 3, 17011715.

L. H. Pearl , C. Prodromou and P. Workman (2008). The Hsp90 molecular chaperone: an open and shut case for treatment. Biochemical Journal 410, 439453.

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

D. Picard , E. Suslova and P. A. Briand (2006). 2-color photobleaching experiments reveal distinct intracellular dynamics of two components of the Hsp90 complex. Experimental Cell Research 312, 39493958.

C. Prodromou and L. H. Pearl (2003). Structure and functional relationships of Hsp90. Current Cancer Drug Targets 3, 301323.

C. Prodromou , S. M. Roe , R. O'Brien , J. E. Ladbury , P. W. Piper and L. H. Pearl (1997). Identification and structural characterization of the ATP/ADP-binding site in the Hsp90 molecular chaperone. Cell 90, 6575.

J. R. Radke , B. Striepen , M. N. Guerini , M. E. Jerome , D. S. Roos and M. W. White (2001). Defining the cell cycle for the tachyzoite stage of Toxoplasma gondii. Molecular and Biochemical Parasitology 115, 165175.

J. R. Radke , M. N. Guerini , M. Jerome and M. W. White (2003). A change in the premitotic period of the cell cycle is associated with bradyzoite differentiation in Toxoplasma gondii. Molecular and Biochemical Parasitology 131, 119127.

M. Retzlaff , F. Hagn , L. Mitschke , M. Hessling , F. Gugel , H. Kessler , K. Richter and J. Buchner (2010). Asymmetric activation of the hsp90 dimer by its cochaperone aha1. Molecular Cell 37, 344354.

A. K. Rochani , M. Singh and U. Tatu (2013). Heat shock protein 90 inhibitors as broad spectrum anti-infectives. Current Pharmaceutical Design 19, 377386.

N. Roy , R. K. Nageshan , S. Ranade and U. Tatu (2012). Heat shock protein 90 from neglected protozoan parasites. Biochimica et Biophysica Acta 1823, 707711.

R. Sawarkar , C. Sievers and R. Paro (2012). Hsp90 globally targets paused RNA polymerase to regulate gene expression in response to environmental stimuli. Cell 149, 807818.

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.

J. Shao , S. D. Hartson and R. L. Matts (2002). Evidence that protein phosphatase 5 functions to negatively modulate the maturation of the Hsp90-dependent heme-regulated eIF2alpha kinase. Biochemistry 41, 67706779.

P. Sharma and C. E. Chitnis (2013). Key molecular events during host cell invasion by Apicomplexan pathogens. Current Opinion in Microbiology 16, 432437.

A. Shonhai , A. G. Maier , J. M. Przyborski and G. L. Blatch (2011). Intracellular protozoan parasites of humans: the role of molecular chaperones in development and pathogenesis. Protein and Peptide Letters 18, 143157.

J. Soroka , S. K. Wandinger , N. Mausbacher , T. Schreiber , K. Richter , H. Daub and J. Buchner (2012). Conformational switching of the molecular chaperone Hsp90 via regulated phosphorylation. Molecular Cell 45, 517528.

C. E. Stebbins , A. A. Russo , C. Schneider , N. Rosen , F. U. Hartl and N. P. Pavletich (1997). Crystal structure of an Hsp90-geldanamycin complex: targeting of a protein chaperone by an antitumor agent. Cell 89, 239250.

B. Striepen , C. N. Jordan , S. Reiff and G. G. van Dooren (2007). Building the perfect parasite: cell division in apicomplexa. PLoS Pathogen 3, e78.

A. M. Tenter , A. R. Heckeroth and L. M. Weiss (2000). Toxoplasma gondii: from animals to humans. International Journal for Parasitology 30, 12171258.

S. Tomavo and J. C. Boothroyd (1995). Interconnection between organellar functions, development and drug resistance in the protozoan parasite, Toxoplasma gondii. International Journal for Parasitology 25, 12931299.

M. Treeck , J. L. Sanders , J. E. Elias and J. C. Boothroyd (2011). The phosphoproteomes of Plasmodium falciparum and Toxoplasma gondii reveal unusual adaptations within and beyond the parasites’ boundaries. Cell Host and Microbe 10, 410419.

S. Tsutsumi , M. Mollapour , C. Graf , C. T. Lee , B. T. Scroggins , W. Xu , L. Haslerova , M. Hessling , A. A. Konstantinova , J. B. Trepel , B. Panaretou , J. Buchner , M. P. Mayer , C. Prodromou and L. Neckers (2009). Hsp90 charged-linker truncation reverses the functional consequences of weakened hydrophobic contacts in the N domain. Nature Structural and Molecular Biology 16, 11411147.

A. Ueno , G. Dautu , K. Haga , B. Munyaka , G. Carmen , Y. Kobayashi and M. Igarashi (2011). Toxoplasma gondii: a bradyzoite-specific DnaK-tetratricopeptide repeat (DnaK-TPR) protein interacts with p23 co-chaperone protein. Experimental Parasitology 127, 795803.

L. Vanagas , V. Jeffers , S. S. Bogado , M. C. Dalmasso , W. J. Sullivan Jr. and S. O. Angel (2012). Toxoplasma histone acetylation remodelers as novel drug targets. Expert Review of Anti-Infective Therapy 10, 11891201.

X. Wang , X. Song , W. Zhuo , Y. Fu , H. Shi , Y. Liang , M. Tong , G. Chang and Y. Luo (2009). The regulatory mechanism of Hsp90alpha secretion and its function in tumor malignancy. Proceedings of the National Academy of Sciences USA 106, 2128821293.

W. Xu , M. Mollapour , C. Prodromou , S. Wang , B. T. Scroggins , Z. Palchick , K. Beebe , M. Siderius , M. J. Lee , A. Couvillon , J. B. Trepel , Y. Miyata , R. Matts and L. Neckers (2012). Dynamic tyrosine phosphorylation modulates cycling of the HSP90-P50(CDC37)-AHA1 chaperone machine. Molecular Cell 47, 434443.

B. Xue , V. Jeffers , W. J. Sullivan and V. N. Uversky (2013). Protein intrinsic disorder in the acetylome of intracellular and extracellular Toxoplasma gondii. Molecular BioSystems 9, 645657.

X. Yu , Z. S. Guo , M. G. Marcu , L. Neckers , D. M. Nguyen , G. A. Chen and D. S. Schrump (2002). Modulation of p53, ErbB1, ErbB2, and Raf-1 expression in lung cancer cells by depsipeptide FR901228. Journal of the National Cancer Institute 94, 504513.

Q. Zhou , A. T. Agoston , P. Atadja , W. G. Nelson and N. E. Davidson (2008). Inhibition of histone deacetylases promotes ubiquitin-dependent proteasomal degradation of DNA methyltransferase 1 in human breast cancer cells. Molecular Cancer Research 6, 873883.

W. Zhou , J. H. Quan , Y. H. Lee , D. W. Shin and G. H. Cha (2013). Proliferation require down-regulation of host Nox4 expression via activation of PI3 Kinase/Akt signaling pathway. PLoS ONE 8, e66306.

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