Skip to main content
×
Home
    • Aa
    • Aa

Progress and prospects for targeting Hsp90 to treat fungal infections

  • AMANDA VERI (a1) and LEAH E. COWEN (a1)
Summary
Summary

Fungal pathogens pose a major threat to human health worldwide. They infect billions of people each year, leading to at least 1·5 million deaths. Treatment of fungal infections is difficult due to the limited number of clinically useful antifungal drugs, and the emergence of drug resistance. A promising new strategy to enhance the efficacy of antifungal drugs and block the evolution of drug resistance is to target the molecular chaperone Hsp90. Pharmacological inhibitors of Hsp90 function that are in development as anticancer agents have potential to be repurposed as agents for combination antifungal therapy for some applications, such as biofilm infections. For systemic infections, however, effective combination therapy regimens may require Hsp90 inhibitors that can selectively target Hsp90 in the pathogen, or alternate strategies to compromise function of the Hsp90 chaperone machine. Selectively impairing Hsp90 function in the pathogen could in principle be achieved by targeting Hsp90 co-chaperones or regulators of Hsp90 function that are more divergent between pathogen and host than Hsp90. Antifungal combination therapies could also exploit downstream effectors of Hsp90 that are critical for fungal drug resistance and virulence. Here, we discuss the progress and prospects for establishing Hsp90 as an important therapeutic target for life-threatening fungal infections.

Copyright
Corresponding author
* Corresponding author: Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Medical Sciences Building, Room 4368, Toronto, Ontario M5S 1A8, Canada. E-mail: leah.cowen@utoronto.ca
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.

T. Bader , B. Bodendorfer , K. Schroppel and J. Morschhauser (2003). Calcineurin is essential for virulence in Candida albicans. Infection and Immunity 71, 53445354.

J. R. Blankenship and A. P. Mitchell (2006). How to build a biofilm: a fungal perspective. Current Opinion in Microbiology 9, 588594.

C. Bock and T. Lengauer (2012). Managing drug resistance in cancer: lessons from HIV therapy. Nature Reviews Cancer 12, 494501. doi: 10.1038/nrc3297.

G. D. Brown , D. W. Denning , N. A. Gow , S. M. Levitz , M. G. Netea and T. C. White (2012 a). Hidden killers: human fungal infections. Science Translational Medicine 4, 165rv113. doi: 10.1126/scitranslmed.3004404.

G. D. Brown , D. W. Denning and S. M. Levitz (2012 b). Tackling human fungal infections. Science 336, 647. doi: 10.1126/science.1222236.

E. J. Byrnes III, K. H. Bartlett , J. R. Perfect and J. Heitman (2011). Cryptococcus gattii: an emerging fungal pathogen infecting humans and animals. Microbes and Infection 13, 895907. doi: 10.1016/j.micinf.2011.05.009.

C. T. Chan , R. E. Reeves , R. Geller , S. S. Yaghoubi , A. Hoehne , D. E. Solow-Cordero , G. Chiosis , T. F. Massoud , R. Paulmurugan and S. S. Gambhir (2012). Discovery and validation of small-molecule heat-shock protein 90 inhibitors through multimodality molecular imaging in living subjects. Proceedings of the National Academy of Sciences USA 109, E2476E2485. doi: 10.1073/pnas.1205459109.

Y. L. Chen , A. Brand , E. L. Morrison , F. G. Silao , U. G. Bigol , F. F. Malbas Jr., J. E. Nett , D. R. Andes , N. V. Solis , S. G. Filler , A. Averette and J. Heitman (2011). Calcineurin controls drug tolerance, hyphal growth, and virulence in Candida dubliniensis. Eukaryotic Cell 10, 803819. doi: 10.1128/EC.00310-10.

Y. L. Chen , J. H. Konieczka , D. J. Springer , S. E. Bowen , J. Zhang , F. G. Silao , A. A. Bungay , U. G. Bigol , M. G. Nicolas , S. N. Abraham , D. A. Thompson , A. Regev and J. Heitman (2012). Convergent evolution of calcineurin pathway roles in thermotolerance and virulence in Candida glabrata. G3:Genes, Genomes, Genetics 2, 675691. doi: 10.1534/g3.112.002279.

Y. L. Chen , V. N. Lehman , Y. Lewit , A. F. Averette and J. Heitman (2013). Calcineurin governs thermotolerance and virulence of Cryptococcus gattii. G3:Genes, Genomes, Genetics 3, 527539. doi: 10.1534/g3.112.004242.

L. E. Cowen (2008). The evolution of fungal drug resistance: modulating the trajectory from genotype to phenotype. Nature Reviews Microbiology 6, 187198.

L. E. Cowen (2009). Hsp90 orchestrates stress response signaling governing fungal drug resistance. PLoS Pathogens 5, e1000471. doi: 10.1371/journal.ppat.1000471.

L. E. Cowen (2013). The fungal Achilles’ heel: targeting Hsp90 to cripple fungal pathogens. Current Opinion in Microbiology 16, 377384. doi: 10.1016/j.mib.2013.03.005.

L. E. Cowen and S. Lindquist (2005). Hsp90 potentiates the rapid evolution of new traits: drug resistance in diverse fungi. Science 309, 21852189.

L. E. Cowen and W. J. Steinbach (2008). Stress, drugs, and evolution: the role of cellular signaling in fungal drug resistance. Eukaryotic Cell 7, 747764.

L. E. Cowen , A. E. Carpenter , O. Matangkasombut , G. R. Fink and S. Lindquist (2006). Genetic architecture of Hsp90-dependent drug resistance. Eukaryotic Cell 5, 21842188.

L. E. Cowen , S. D. Singh , J. R. Kohler , C. Collins , A. K. Zaas , W. A. Schell , H. Aziz , E. Mylonakis , J. R. Perfect , L. Whitesell and S. Lindquist (2009). Harnessing Hsp90 function as a powerful, broadly effective therapeutic strategy for fungal infectious disease. Proceedings of the National Academy of Sciences USA 106, 2828–2823. doi: 10.1073/pnas.0813394106.

M. C. Cruz , A. L. Goldstein , J. R. Blankenship , M. Del Poeta , D. Davis , M. E. Cardenas , J. R. Perfect , J. H. McCusker and J. Heitman (2002). Calcineurin is essential for survival during membrane stress in Candida albicans. EMBO Journal 21, 546559.

C. d'Enfert (2006). Biofilms and their role in the resistance of pathogenic Candida to antifungal agents. Current Drug Targets 7, 465470.

S. Diezmann , M. Michaut , R. S. Shapiro , G. D. Bader and L. E. Cowen (2012). Mapping the Hsp90 genetic interaction network in Candida albicans reveals environmental contingency and rewired circuitry. PLoS Genetics 8, e1002562. doi: 10.1371/journal.pgen.1002562.

L. T. Donlin , C. Andresen , S. Just , E. Rudensky , C. T. Pappas , M. Kruger , E. Y. Jacobs , A. Unger , A. Zieseniss , M. W. Dobenecker , T. Voelkel , B. T. Chait , C. C. Gregorio , W. Rottbauer , A. Tarakhovsky and W. A. Linke (2012). Smyd2 controls cytoplasmic lysine methylation of Hsp90 and myofilament organization. Genes and Development 26, 114119. doi: 10.1101/gad.177758.111.

S. F. Falsone , S. Leptihn , A. Osterauer , M. Haslbeck and J. Buchner (2004). Oncogenic mutations reduce the stability of SRC kinase. Journal of Molecular Biology 344, 281291.

J. S. Finkel and A. P. Mitchell (2011). Genetic control of Candida albicans biofilm development. Nature Reviews Microbiology 9, 109118. doi: 10.1038/nrmicro2475.

M. C. Fisher , D. A. Henk , C. J. Briggs , J. S. Brownstein , L. C. Madoff , S. L. McCraw and S. J. Gurr (2012). Emerging fungal threats to animal, plant and ecosystem health. Nature 484, 186194. doi: 10.1038/nature10947.

K. J. Gerik , M. J. Donlin , C. E. Soto , A. M. Banks , I. R. Banks , M. A. Maligie , C. P. Selitrennikoff and J. K. Lodge (2005). Cell wall integrity is dependent on the PKC1 signal transduction pathway in Cryptococcus neoformans. Molecular Microbiology 58, 393408. doi: 10.1111/j.1365-2958.2005.04843.x.

J. Imai and I. Yahara (2000). Role of HSP90 in salt stress tolerance via stabilization and regulation of calcineurin. Molecular and Cellular Biology 20, 92629270.

D. F. Jarosz and S. Lindquist (2010). Hsp90 and environmental stress transform the adaptive value of natural genetic variation. Science 330, 18201824. doi: 10.1126/science.1195487.

J. L. Johnson and C. Brown (2009). Plasticity of the Hsp90 chaperone machine in divergent eukaryotic organisms. Cell Stress and Chaperones 14, 8394. doi: 10.1007/s12192-008-0058-9.

P. R. Juvvadi , C. Gehrke , J. R. Fortwendel , F. Lamoth , E. J. Soderblom , E. C. Cook , M. A. Hast , Y. G. Asfaw , M. A. Moseley , T. P. Creamer and W. J. Steinbach (2013). Phosphorylation of calcineurin at a novel serine-proline rich region orchestrates hyphal growth and virulence in Aspergillus fumigatus. PLoS Pathogens 9, e1003564. doi: 10.1371/journal.ppat.1003564.

S. L. LaFayette , C. Collins , A. K. Zaas , W. A. Schell , M. Betancourt-Quiroz , A. A. Gunatilaka , J. R. Perfect and L. E. Cowen (2010). PKC signaling regulates drug resistance of the fungal pathogen Candida albicans via circuitry comprised of Mkc1, calcineurin, and Hsp90. PLoS Pathogens 6, e1001090. doi: 10.1371/journal.ppat.1001069.

F. Lamoth , P. R. Juvvadi , C. Gehrke and W. J. Steinbach (2012). In vitro activity of calcineurin and heat-shock protein 90 (Hsp90) inhibitors against Aspergillus fumigatus azole- and echinocandin-resistant strains. Antimicrobial Agents and Chemotherapy 57, 10351039. doi: 10.1128/AAC.01857-12.

M. D. Leach , E. Klipp , L. E. Cowen and A. J. Brown (2012). Fungal Hsp90: a biological transistor that tunes cellular outputs to thermal inputs. Nature Reviews Microbiology 10, 693704. doi: 10.1038/nrmicro2875.

S. J. Lin , J. Schranz and S. M. Teutsch (2001). Aspergillosis case-fatality rate: systematic review of the literature. Clinical Infectious Diseases 32, 358366. doi: 10.1086/318483.

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. doi: 10.1073/pnas.0407294102.

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. doi: 10.1016/j.cell.2007.07.036.

L. G. Miller , R. A. Hajjeh and J. E. Edwards Jr. (2001). Estimating the cost of nosocomial candidemia in the United States. Clinical Infectious Diseases 32, 1110. doi: 10.1086/319613.

S. H. Millson , A. W. Truman , V. King , C. Prodromou , L. H. Pearl and P. W. Piper (2005). A two-hybrid screen of the yeast proteome for Hsp90 interactors uncovers a novel Hsp90 chaperone requirement in the activity of a stress-activated mitogen-activated protein kinase, Slt2p (Mpk1p). Eukaryotic Cell 4, 849860. doi: 10.1128/EC.4.5.849-860.2005.

T. Miyazaki , T. Inamine , S. Yamauchi , Y. Nagayoshi , T. Saijo , K. Izumikawa , M. Seki , H. Kakeya , Y. Yamamoto , K. Yanagihara , Y. Miyazaki and S. Kohno (2010 a). Role of the Slt2 mitogen-activated protein kinase pathway in cell wall integrity and virulence in Candida glabrata . FEMS Yeast Research 10, 343352. doi: 10.1111/j.1567-1364.2010.00611.x.

T. Miyazaki , S. Yamauchi , T. Inamine , Y. Nagayoshi , T. Saijo , K. Izumikawa , M. Seki , H. Kakeya , Y. Yamamoto , K. Yanagihara , Y. Miyazaki and S. Kohno (2010 b). Roles of calcineurin and Crz1 in antifungal susceptibility and virulence of Candida glabrata. Antimicrobial Agents and Chemotherapy 54, 16391643. doi: 10.1128/AAC.01364-09.

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). Swe1Wee1-dependent tyrosine phosphorylation of Hsp90 regulates distinct facets of chaperone function. Molecular Cell 37, 333343.

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). Threonine 22 phosphorylation attenuates Hsp90 interaction with cochaperones and affects its chaperone activity. Molecular Cell 41, 672681. doi: 10.1016/j.molcel.2011.02.011.

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.

L. Neckers and P. Workman (2012). Hsp90 molecular chaperone inhibitors: are we there yet? Clinical Cancer Research 18, 6476. doi: 10.1158/1078-0432.CCR-11-1000.

J. Nett and D. Andes (2006). Candida albicans biofilm development, modeling a host-pathogen interaction. Current Opinion in Microbiology 9, 340345.

S. M. Noble , S. French , L. A. Kohn , V. Chen and A. D. Johnson (2010). Systematic screens of a Candida albicans homozygous deletion library decouple morphogenetic switching and pathogenicity. Nature Genetics 42, 590598. doi: 10.1038/ng.605.

R. Pallavi , N. Roy , R. K. Nageshan , P. Talukdar , S. R. Pavithra , R. Reddy , S. Venketesh , R. Kumar , A. K. Gupta , R. K. Singh , S. C. Yadav and U. Tatu (2010). Heat shock protein 90 as a drug target against protozoan infections: biochemical characterization of HSP90 from Plasmodium falciparum and Trypanosoma evansi and evaluation of its inhibitor as a candidate drug. Journal of Biological Chemistry 285, 3796437975. doi: 10.1074/jbc.M110.155317.

P. D. Patel , P. Yan , P. M. Seidler , H. J. Patel , W. Sun , C. Yang , N. S. Que , T. Taldone , P. Finotti , R. A. Stephani , D. T. Gewirth and G. Chiosis (2013). Paralog-selective Hsp90 inhibitors define tumor-specific regulation of HER2. Nature Chemical Biology 9, 677684. doi: 10.1038/nchembio.1335.

M. A. Pfaller and D. J. Diekema (2007). Epidemiology of invasive candidiasis: a persistent public health problem. Clinical Microbiology Reviews 20, 133163.

M. A. Pfaller and D. J. Diekema (2010). Epidemiology of invasive mycoses in North America. Critical Reviews in Microbiology 36, 153.

J. C. Pizarro , T. Hills , G. Senisterra , A. K. Wernimont , C. Mackenzie , N. R. Norcross , M. A. Ferguson , P. G. Wyatt , I. H. Gilbert and R. Hui (2013). Exploring the Trypanosoma brucei Hsp83 potential as a target for structure guided drug design. PLoS Neglected Tropical Diseases 7, e2492. doi: 10.1371/journal.pntd.0002492.

C. Queitsch , T. A. Sangster and S. Lindquist (2002). Hsp90 as a capacitor of phenotypic variation. Nature 417, 618624.

G. Ramage , E. Mowat , B. Jones , C. Williams and J. Lopez-Ribot (2009). Our current understanding of fungal biofilms. Critical Reviews in Microbiology 35, 340355. doi: 10.3109/10408410903241436.

J. L. Reedy , S. G. Filler and J. Heitman (2010). Elucidating the Candida albicans calcineurin signaling cascade controlling stress response and virulence. Fungal Genetics and Biology 47, 107116. doi: 10.1016/j.fgb.2009.09.002.

N. Robbins , P. Uppuluri , J. Nett , R. Rajendran , G. Ramage , J. L. Lopez-Ribot , D. Andes and L. E. Cowen (2011). Hsp90 governs dispersion and drug resistance of fungal biofilms. PLoS Pathogens 7, e1002257. doi: 10.1371/journal.ppat.1002257.

N. Robbins , M. D. Leach and L. E. Cowen (2012). Lysine deacetylases Hda1 and Rpd3 regulate Hsp90 function thereby governing fungal drug resistance. Cell Reports 2, 878888. doi: 10.1016/j.celrep.2012.08.035.

S. L. Rutherford (2003). Between genotype and phenotype: protein chaperones and evolvability. Nature Reviews Genetics 4, 263274.

S. L. Rutherford and S. Lindquist (1998). Hsp90 as a capacitor for morphological evolution. Nature 396, 336342.

D. Sanglard , F. Ischer , O. Marchetti , J. Entenza and J. Bille (2003). Calcineurin A of Candida albicans: involvement in antifungal tolerance, cell morphogenesis and virulence. Molecular Microbiology 48, 959976.

T. A. Sangster , S. Lindquist and C. Queitsch (2004). Under cover: causes, effects and implications of Hsp90-mediated genetic capacitance. BioEssays 26, 348362.

T. A. Sangster , N. Salathia , H. N. Lee , E. Watanabe , K. Schellenberg , K. Morneau , H. Wang , S. Undurraga , C. Queitsch and S. Lindquist (2008 a). HSP90-buffered genetic variation is common in Arabidopsis thaliana. Proceedings of the National Academy of Sciences USA 105, 29692974. doi: 10.1073/pnas.0712210105.

T. A. Sangster , N. Salathia , S. Undurraga , R. Milo , K. Schellenberg , S. Lindquist and C. Queitsch (2008 b). HSP90 affects the expression of genetic variation and developmental stability in quantitative traits. Proceedings of the National Academy of Sciences USA 105, 29632968. doi: 10.1073/pnas.0712200105.

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.

D. Shahinas , M. Liang , A. Datti and D. R. Pillai (2010). A repurposing strategy identifies novel synergistic inhibitors of Plasmodium falciparum heat shock protein 90. Journal of Medicinal Chemistry 53, 35523557. doi: 10.1021/jm901796s.

D. Shahinas , G. Macmullin , C. Benedict , I. Crandall and D. R. Pillai (2012). Harmine is a potent antimalarial targeting Hsp90 and synergizes with chloroquine and artemisinin. Antimicrobial Agents and Chemotherapy 56, 42074213. doi: 10.1128/AAC.00328-12.

D. Shahinas , A. Folefoc , T. Taldone , G. Chiosis , I. Crandall and D. R. Pillai (2013). A purine analog synergizes with chloroquine (CQ) by targeting Plasmodium falciparum Hsp90 (PfHsp90). PLoS ONE 8, e75446. doi: 10.1371/journal.pone.0075446.

R. S. Shapiro , P. Uppuluri , A. K. Zaas , C. Collins , H. Senn , J. R. Perfect , J. Heitman and L. E. Cowen (2009). Hsp90 orchestrates temperature-dependent Candida albicans morphogenesis via Ras1-PKA signaling. Current Biology 19, 621629.

R. S. Shapiro , N. Robbins and L. E. Cowen (2011). Regulatory circuitry governing fungal development, drug resistance, and disease. Microbiology and Molecular Biology Reviews 75, 213267. doi: 10.1128/MMBR.00045-10.

R. S. Shapiro , A. Sellam , F. Tebbji , M. Whiteway , A. Nantel and L. E. Cowen (2012 a). Pho85, Pcl1, and Hms1 signaling governs Candida albicans morphogenesis induced by high temperature or Hsp90 compromise. Current Biology 22, 461470. doi: 10.1016/j.cub.2012.01.062.

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

S. D. Singh , N. Robbins , A. K. Zaas , W. A. Schell , J. R. Perfect and L. E. Cowen (2009). Hsp90 governs echinocandin resistance in the pathogenic yeast Candida albicans via calcineurin. PLoS Pathogens 5, e1000532. doi: 10.1371/journal.ppat.1000532.

S. D. Singh-Babak , T. Babak , S. Diezmann , J. A. Hill , J. L. Xie , Y. L. Chen , S. M. Poutanen , R. P. Rennie , J. Heitman and L. E. Cowen (2012). Global analysis of the evolution and mechanism of echinocandin resistance in Candida glabrata. PLoS Pathogens 8, e1002718. doi: 10.1371/journal.ppat.1002718.

V. Sollars , X. Lu , L. Xiao , X. Wang , M. D. Garfinkel and D. M. Ruden (2003). Evidence for an epigenetic mechanism by which Hsp90 acts as a capacitor for morphological evolution. Nature Genetics 33, 7074.

D. R. Southworth and D. A. Agard (2008). Species-dependent ensembles of conserved conformational states define the Hsp90 chaperone ATPase cycle. Molecular Cell 32, 631640. doi: 10.1016/j.molcel.2008.10.024.

V. Specchia , L. Piacentini , P. Tritto , L. Fanti , R. D'Alessandro , G. Palumbo , S. Pimpinelli and M. P. Bozzetti (2010). Hsp90 prevents phenotypic variation by suppressing the mutagenic activity of transposons. Nature 463, 662665. doi: 10.1038/nature08739.

W. J. Steinbach , R. A. Cramer Jr., B. Z. Perfect , Y. G. Asfaw , T. C. Sauer , L. K. Najvar , W. R. Kirkpatrick , T. F. Patterson , D. K. Benjamin Jr., J. Heitman and J. R. Perfect (2006). Calcineurin controls growth, morphology, and pathogenicity in Aspergillus fumigatus. Eukaryotic Cell 5, 10911103.

W. J. Steinbach , J. L. Reedy , R. A. Cramer Jr., J. R. Perfect and J. Heitman (2007). Harnessing calcineurin as a novel anti-infective agent against invasive fungal infections. Nature Reviews Microbiology 5, 418430.

M. Taipale , D. F. Jarosz and S. Lindquist (2010). HSP90 at the hub of protein homeostasis: emerging mechanistic insights. Nature Reviews Molecular Cell Biology 11, 515528. doi: 10.1038/nrm2918.

M. Tariq , U. Nussbaumer , Y. Chen , C. Beisel and R. Paro (2009). Trithorax requires Hsp90 for maintenance of active chromatin at sites of gene expression. Proceedings of the National Academy of Sciences USA 106, 11571162. doi: 10.1073/pnas.0809669106.

J. Trepel , M. Mollapour , G. Giaccone and L. Neckers (2010). Targeting the dynamic HSP90 complex in cancer. Nature Reviews Cancer 10, 537549. doi: 10.1038/nrc2887.

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. doi: 10.1016/j.molcel.2012.05.015.

Y. Xu and S. Lindquist (1993). Heat-shock protein Hsp90 governs the activity of pp60v-src kinase. Proceedings of the National Academy of Sciences USA 90, 70747078.

Y. Xu , M. A. Singer and S. Lindquist (1999). Maturation of the tyrosine kinase c-src as a kinase and as a substrate depends on the molecular chaperone Hsp90. Proceedings of the National Academy of Sciences USA 96, 109114.

J. Zhang , F. G. Silao , U. G. Bigol , A. A. Bungay , M. G. Nicolas , J. Heitman and Y. L. Chen (2012). Calcineurin is required for pseudohyphal growth, virulence, and drug resistance in Candida lusitaniae. PLoS ONE 7, e44192. doi: 10.1371/journal.pone.0044192.

R. Zhao , M. Davey , Y. C. Hsu , P. Kaplanek , A. Tong , A. B. Parsons , N. Krogan , G. Cagney , D. Mai , J. Greenblatt , C. Boone , A. Emili and W. A. Houry (2005). Navigating the chaperone network: an integrative map of physical and genetic interactions mediated by the Hsp90 chaperone. Cell 120, 715727.

A. Zumla , R. Hafner , C. Lienhardt , M. Hoelscher and A. Nunn (2012). Advancing the development of tuberculosis therapy. Nature Reviews Drug Discovery 11, 171172. doi: 10.1038/nrd3694.

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

Altmetric attention score

Full text views

Total number of HTML views: 6
Total number of PDF views: 32 *
Loading metrics...

Abstract views

Total abstract views: 192 *
Loading metrics...

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