1887

Abstract

is an important human fungal pathogen that also serves as a model for studies of fungal pathogenesis. contains several genes encoding peptidyl-prolyl / isomerases (PPIases), enzymes that catalyse changes in the folding and conformation of target proteins. Three distinct classes of PPIases have been identified: cyclophilins, FK506-binding proteins (FKBPs) and parvulins. This paper reports the cloning and characterization of , which is believed to be the first (and probably only) parvulin-class PPIase in . It is shown that from is structurally and functionally homologous to from , which encodes an essential PPIase that interacts with RNA polymerase II and plays a role in transcription. In , was found to be dispensable for growth, haploid fruiting and capsule formation. However, was required for virulence in a murine model of cryptococcosis. Loss of virulence might have been due to the defects in melanin and urease production observed in mutants, or to defects in transcription of as-yet-unidentified virulence genes. The fact that Ess1 is not essential in suggests that, in this organism, some of its functions might be subsumed by other prolyl isomerases, in particular, cyclophilins Cpa1 or Cpa2. This is supported by the finding that mutants were hypersensitive to cyclosporin A. might therefore be a useful organism in which to investigate crosstalk among different families of prolyl isomerases.

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2005-05-01
2019-11-18
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References

  1. Alspaugh, J. A., Perfect, J. R. & Heitman, J. ( 1997; ). Cryptococcus neoformans mating and virulence are regulated by the G-protein α subunit GPA1 and cAMP. Genes Dev 11, 3206–3217.[CrossRef]
    [Google Scholar]
  2. Arévalo-Rodríguez, M., Cardenas, M. E., Wu, X., Hanes, S. D. & Heitman, J. ( 2000; ). Cyclophilin A and Ess1 interact with and regulate silencing by the Sin3-Rpd3 histone deacetylase. EMBO J 19, 3739–3749.[CrossRef]
    [Google Scholar]
  3. Arévalo-Rodríguez, M., Wu, X., Hanes, S. D. & Heitman, J. ( 2004; ). Prolyl isomerases in yeast. Front Biosci 9, 2420–2446.[CrossRef]
    [Google Scholar]
  4. Chang, Y. C. & Kwon-Chung, K. J. ( 1994; ). Complementation of a capsule-deficient mutation of Cryptococcus neoformans restores its virulence. Mol Cell Biol 14, 4912–4919.
    [Google Scholar]
  5. Cox, G. M., Mukherjee, J., Cole, G. T., Casadevall, A. & Perfect, J. R. ( 2000; ). Urease as a virulence factor in experimental cryptococcosis. Infect Immun 68, 443–448.[CrossRef]
    [Google Scholar]
  6. Crenshaw, D. G., Yang, J., Means, A. R. & Kornbluth, S. ( 1998; ). The mitotic peptidyl-prolyl isomerase, Pin1, interacts with Cdc25 and Plx1. EMBO J 17, 1315–1327.[CrossRef]
    [Google Scholar]
  7. Cruz, M. C., Cavallo, L. M., Gorlach, J. M., Cox, G., Perfect, J. R., Cardenas, M. E. & Heitman, J. ( 1999; ). Rapamycin antifungal action is mediated via conserved complexes with FKBP12 and TOR kinase homologs in Cryptococcus neoformans. Mol Cell Biol 19, 4101–4112.
    [Google Scholar]
  8. Cruz, M. C., Goldstein, A. L., Blankenship, J., Del Poeta, M., Perfect, J. R., McCusker, J. H., Bennani, Y. L., Cardenas, M. E. & Heitman, J. ( 2001; ). Rapamycin and less immunosuppressive analogs are toxic to Candida albicans and Cryptococcus neoformans via FKBP12-dependent inhibition of TOR. Antimicrob Agents Chemother 45, 3162–3170.[CrossRef]
    [Google Scholar]
  9. Davidson, R. C., Cruz, M. C., Sia, R. A. L., Allen, B., Alspaugh, A. & Heitman, J. ( 2000; ). Gene disruption by biolistic transformation in serotype D strain of Cryptococcus neoformans. Fungal Genet Biol 29, 38–48.[CrossRef]
    [Google Scholar]
  10. Devasahayam, G., Chaturvedi, V. & Hanes, S. D. ( 2002; ). The Ess1 prolyl isomerase is required for growth and morphogenetic switching in Candida albicans. Genetics 160, 37–48.
    [Google Scholar]
  11. Dolinski, K. & Heitman, J. ( 1997; ). Peptidyl-prolyl isomerases – an overview of the cyclophilin, FKBP and parvulin families. In Guidebook to Molecular Chaperones and Protein Folding Catalysis, pp. 359–369. Edited by M. J. Gething. Oxford: Oxford University Press.
  12. Dolinski, K., Muir, S., Cardenas, M. & Heitman, J. ( 1997; ). All cyclophilins and FK506 binding proteins are, individually and collectively, dispensable for viability in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 94, 13093–13098.[CrossRef]
    [Google Scholar]
  13. Edman, J. & Kwon-Chung, K. J. ( 1990; ). Isolation of the URA5 gene from Cryptococcus neoformans var. neoformans and its use as a selective marker for transformation. Mol Cell Biol 10, 4538–4544.
    [Google Scholar]
  14. Erickson, T., Liu, L., Gueyikian, A., Zhu, A. X., Gibbons, J. & Williamson, P. R. ( 2001; ). Multiple virulence factors of Cryptococcus neoformans are dependent on VPH1. Mol Microbiol 42, 1121–1131.[CrossRef]
    [Google Scholar]
  15. Fischer, G. ( 1994; ). Peptidyl-prolyl cis/trans isomerases and their effectors. Angew Chem Int Ed Engl 33, 1415–1436.[CrossRef]
    [Google Scholar]
  16. Fischer, G., Tradler, T. & Zarnt, T. ( 1998; ). The mode of action of peptidyl prolyl cis/trans isomerases in vivo: binding vs catalysis. FEBS Lett 426, 17–20.[CrossRef]
    [Google Scholar]
  17. Fromtling, R. A., Shadomy, H. J. & Jacobson, E. S. ( 1982; ). Decreased virulence in stable, acapsular mutants of Cryptococcus neoformans. Mycopathologia 79, 23–29.[CrossRef]
    [Google Scholar]
  18. Fujimori, F., Takahashi, K., Uchida, C. & Uchida, T. ( 1999; ). Mice lacking Pin1 develop normally, but are defective in entering cell cycle from G0 arrest. Biochem Biophys Res Commun 265, 658–663.[CrossRef]
    [Google Scholar]
  19. Fujimori, F., Gunji, W., Kikuchi, J. & 7 other authors ( 2001; ). Crosstalk of prolyl isomerases, Pin1/Ess1, and cyclophilin A. Biochem Biophys Res Commun 289, 181–190.[CrossRef]
    [Google Scholar]
  20. Gemmill, T., Wu, X. & Hanes, S. D. ( 2005; ). Vanishingly low levels of Ess1 prolyl-isomerase activity are sufficient for growth in Saccharomyces cerevisiae. J Biol Chem (in press).
    [Google Scholar]
  21. Guthrie, C. & Fink, G. R. ( 1991; ). Guide to yeast genetics and molecular biology. Methods Enzymol 194, 3–21.
    [Google Scholar]
  22. Gyuris, J., Golemis, E., Chertkov, H. & Brent, R. ( 1993; ). Cdi1, a human G1 and S phase protein phosphatase that associates with Cdk2. Cell 75, 791–803.[CrossRef]
    [Google Scholar]
  23. Handschumacher, R. E., Harding, M. W., Rice, J., Drugge, R. J. & Speicher, D. W. ( 1984; ). Cyclophilin: a specific cytosolic binding protein for cyclosporin A. Science 226, 544–547.[CrossRef]
    [Google Scholar]
  24. Hanes, S. D., Shank, P. R. & Bostian, K. A. ( 1989; ). Sequence and mutational analysis of ESS1, a gene essential for growth in Saccharomyces cerevisiae. Yeast 5, 55–72.[CrossRef]
    [Google Scholar]
  25. Hani, J., Stumpf, G. & Domdey, H. ( 1995; ). PTF1 encodes an essential protein in Saccharomyces cerevisiae, which shows strong homology with a new putative family of PPIases. FEBS Lett 365, 198–202.[CrossRef]
    [Google Scholar]
  26. Horton, R. M., Cai, Z., Ho, S. N. & Pease, L. R. ( 1990; ). Gene splicing by overlap extension: tailor-made genes using the polymerase chain reaction. Biotechniques 8, 528–535.
    [Google Scholar]
  27. Hsu, T., McRackan, D., Vincent, T. S. & Gert de Couet, H. ( 2001; ). Drosophila Pin1 prolyl isomerase Dodo is a MAP kinase signal responder during oogenesis. Nat Cell Biol 3, 538–543.[CrossRef]
    [Google Scholar]
  28. Huang, H.-K., Forsburg, S. L., John, U. P., O'Connell, M. J. & Hunter, T. ( 2001; ). Isolation and characterization of the Pin1/Ess1p homologue in Schizosaccharomyces pombe. J Cell Sci 114, 3779–3788.
    [Google Scholar]
  29. Hunter, T. ( 1998; ). Prolyl isomerases and nuclear function. Cell 92, 141–143.[CrossRef]
    [Google Scholar]
  30. Ikeda, R. & Jacobson, E. S. ( 1992; ). Heterogeneity of phenol oxidases in Cryptococcus neoformans. Infect Immun 60, 3552–3555.
    [Google Scholar]
  31. Ito, H., Fukuda, Y., Murata, K. & Kimura, A. ( 1983; ). Transformation of intact yeast cells treated with alkali cations. J Bacteriol 153, 163–168.
    [Google Scholar]
  32. Joseph, J. D., Daigle, S. N. & Means, A. R. ( 2004; ). PINA is essential for growth and positively influences NIMA function in Aspergillus nidulans. J Biol Chem 279, 32373–32384.[CrossRef]
    [Google Scholar]
  33. Kozel, T. R. ( 1995; ). Virulence factors of Cryptococcus neoformans. Trends Microbiol 3, 295–299.[CrossRef]
    [Google Scholar]
  34. Kozel, T. R. & Cazin, J., Jr ( 1971; ). Nonencapsulated variant of Cryptococcus noeformans. I. Virulence studies and characterization of soluble polysaccharide. Infect Immun 3, 287–294.
    [Google Scholar]
  35. Kwon-Chung, K. J. ( 1978; ). Heterothallism vs. self-fertile isolates of Filobasidiella neoformans (Cryptococcus neoformans). In The Black and White Yeasts. (Proceedings of the IV International Conference on Mycoses, Pan American Health Organization Scientific Publication no. 356), pp. 204–213. Washington, DC: Pan American Health Organization.
  36. Kwon-Chung, K. J., Edman, J. C. & Wickes, B. L. ( 1992a; ). Genetic association of mating types and virulence in Cryptococcus neoformans. Infect Immun 60, 602–605.
    [Google Scholar]
  37. Kwon-Chung, K. J., Varma, A., Edman, J. C. & Bennett, J. E. ( 1992b; ). Selection of ura5 and ura3 mutants from the two varieties of Cryptococcus neoformans on 5-fluoroorotic acid medium. J Med Vet Mycol 30, 61–69.[CrossRef]
    [Google Scholar]
  38. Li, Z., Li, H.-M., Devasahayam, G., Gemmill, T., Chaturvedi, V., Hanes, S. D. & Van Roey, P. ( 2005; ). Structure of the Candida albicans Ess1 prolyl isomerase reveals a well-ordered linker that restricts domain mobility. Biochemistry (in press).
    [Google Scholar]
  39. Liu, L., Tewari, R. P. & Williamson, P. R. ( 1999; ). Laccase protects Cryptococcus neoformans from antifungal activity of alveolar macrophages. Infect Immun 67, 6034–6039.
    [Google Scholar]
  40. Lu, K.-P., Hanes, S. D. & Hunter, T. ( 1996; ). A human peptidyl-prolyl isomerase essential for regulation of mitosis. Nature 380, 544–547.[CrossRef]
    [Google Scholar]
  41. Maleszka, R., Hanes, S. D., Hackett, R. L., DeCouet, H. G. & Miklos, G. L. G. ( 1996; ). The Drosophila melanogaster dodo (dod) gene, conserved in humans, is functionally interchangeable with the ESS1 cell division gene of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 93, 447–451.[CrossRef]
    [Google Scholar]
  42. McGinnis, M. R. ( 1980; ). Laboratory Handbook of Medical Mycology. New York: Academic Press.
  43. Mitchell, T. G. & Perfect, J. R. ( 1995; ). Cryptococcosis in the era of AIDS – 100 years after the discovery of Cryptococcus neoformans. Clin Microbiol Rev 8, 515–548.
    [Google Scholar]
  44. Moore, T. D. E. & Edman, J. C. ( 1993; ). The alpha-mating type locus of Cryptococcus neoformans contains a peptide pheromone gene. Mol Cell Biol 13, 1962–1970.
    [Google Scholar]
  45. Morris, D. P., Phatanani, H. P. & Greenleaf, A. L. ( 1999; ). Phosphocarboxyl-terminal domain binding and the role of a prolyl isomerase in pre-mRNA3′-end formation. J Biol Chem 274, 31583–31587.[CrossRef]
    [Google Scholar]
  46. Odom, A., Muir, S., Lim, E., Toffaletti, D. L., Perfect, J. & Heitman, J. ( 1997; ). Calcineurin is required for virulence of Cryptococcus neoformans. EMBO J 16, 2576–2589.[CrossRef]
    [Google Scholar]
  47. Pierini, L. M. & Doering, T. L. ( 2001; ). Spatial and temporal sequence of capsule construction in Cryptococcus neoformans. Mol Microbiol 41, 105–115.[CrossRef]
    [Google Scholar]
  48. Pukkila-Worley, R., Gerrald, Q. D., Kraus, P. R., Boily, M. J., Davis, M. J., Giles, S. S., Cox, G. M., Heitman, J. & Alspaugh, J. A. ( 2005; ). Transcriptional network of multiple capsule and melanin genes governed by the Cryptococcus neoformans cyclic AMP cascade. Eukaryot Cell 4, 190–201.[CrossRef]
    [Google Scholar]
  49. Rahfeld, J. U., Schierhorn, A., Mann, K. & Fischer, G. ( 1994; ). A novel peptidyl-prolyl cis/trans isomerase from Escherichia coli. FEBS Lett 343, 65–69.[CrossRef]
    [Google Scholar]
  50. Ranganathan, R., Lu, K. P., Hunter, T. & Noel, J. P. ( 1997; ). Structural and functional analysis of the mitotic rotammase Pin1 suggests substrate recognition is phosphorylation dependent. Cell 89, 875–886.[CrossRef]
    [Google Scholar]
  51. Salas, S. D., Bennett, J. E., Kwon-Chung, K. J., Perfect, J. R. & Williamson, P. R. ( 1996; ). Effect of the laccase gene CNLAC1, on virulence of Cryptococcus neoformans. J Exp Med 184, 377–386.[CrossRef]
    [Google Scholar]
  52. Salkin, I. F. ( 1979; ). Further simplification of the Guizotia abyssinica seed medium for identification of Cryptococcus neoformans and Cryptococcus bacillispora. Can J Microbiol 25, 1116–1118.[CrossRef]
    [Google Scholar]
  53. Schiene, C. & Fischer, G. ( 2000; ). Enzymes that catalyse the restructuring of proteins. Curr Opin Struct Biol 10, 40–45.[CrossRef]
    [Google Scholar]
  54. Schmid, F. X., Mayr, L. M., Mucke, M. & Schonbrunner, E. R. ( 1993; ). Prolyl isomerases: role in protein folding. Adv Protein Chem 44, 25–66.
    [Google Scholar]
  55. Shaw, P. E. ( 2002; ). Peptidyl-prolyl isomerases: a new twist to transcription. EMBO Rep 3, 521–526.[CrossRef]
    [Google Scholar]
  56. Shen, M., Stukenberg, P. T., Kirschner, M. W. & Lu, K. P. ( 1998; ). The essential mitotic peptidyl-prolyl isomerase Pin1 binds and regulates mitosis-specific phosphoproteins. Gene Dev 12, 706–720.[CrossRef]
    [Google Scholar]
  57. Stukenberg, P. T. & Kirschner, M. W. ( 2001; ). Pin1 acts catalytically to promote a conformational change in Cdc25. Mol Cell 7, 1071–1083.[CrossRef]
    [Google Scholar]
  58. Sudol, M. ( 1996; ). Structure and function of the WW domain. Prog Biophys Mol Biol 65, 113–132.
    [Google Scholar]
  59. Swofford, D. L. ( 2000; ). paup*, Phylogenetic Analysis Using Parsimony (*and Other Methods), Version 4. Sunderland, MA: Sinauer Associates.
  60. Takahashi, N., Hayano, T. & Suzuki, M. ( 1989; ). Peptidyl-prolyl cis-trans isomerase is the cyclosporin A-binding protein cyclophilin. Nature 337, 473–475.[CrossRef]
    [Google Scholar]
  61. Toffaletti, D. L., Rude, T. H., Johnston, S. A., Durack, D. T. & Perfect, J. R. ( 1993; ). Gene transfer in Cryptococcus neoformans by use of biolistic delivery of DNA. J Bacteriol 175, 1405–1411.
    [Google Scholar]
  62. Wang, P., Cardenas, M. E., Cox, G. M., Perfect, J. R. & Heitman, J. ( 2001; ). Two cyclophilin A homologs with shared and distinct functions important for growth and virulence of Cryptococcus neoformans. EMBO Rep 2, 511–518.[CrossRef]
    [Google Scholar]
  63. Wilcox, C. B., Rossettini, A. & Hanes, S. D. ( 2004; ). Genetic interactions with C-terminal domain (CTD) kinases and the CTD of RNA PolI suggest a role for ESS1 in transcription and elongation in Saccharomyces cerevisiae. Genetics 167, 93–105.[CrossRef]
    [Google Scholar]
  64. Winkler, K. E., Swenson, K. I., Kornbluth, S. & Means, A. R. ( 2000; ). Requirement of the prolyl isomerase Pin1 for the replication checkpoint. Science 287, 1644–1647.[CrossRef]
    [Google Scholar]
  65. Wu, X., Wilcox, C. B., Devasahayam, G., Hackett, R. L., Arévalo-Rodríguez, M., Cardenas, M. E., Heitman, J. & Hanes, S. D. ( 2000; ). The Ess1 prolyl isomerase is linked to chromatin remodeling complexes and the general transcription machinery. EMBO J 19, 3727–3738.[CrossRef]
    [Google Scholar]
  66. Wu, X., Chang, A., Sudol, M. & Hanes, S. D. ( 2001; ). Genetic interactions between the Ess1 prolyl-isomerase and the RSP5 ubiquitin ligase reveal opposing effects on RNA polymerase II function. Curr Genet 40, 234–242.[CrossRef]
    [Google Scholar]
  67. Wu, X., Rossettini, A. & Hanes, S. D. ( 2003; ). The ESS1 prolyl isomerase and its suppressor BYE1 interacts with RNA pol II to inhibit transcription elongation in Saccharomyces cerevisiae. Genetics 165, 1687–1702.
    [Google Scholar]
  68. Xu, Y. X., Hirose, Y., Zhou, X. Z., Lu, K. P. & Manley, J. L. ( 2003; ). Pin1 modulates the structure and function of human RNA polymerase II. Genes Dev 17, 2765–2776.[CrossRef]
    [Google Scholar]
  69. Zhu, X., Gibbons, J., Zhang, S. & Williamson, P. R. ( 2003; ). Copper-mediated reversal of defective laccase in a Δvph1 avirulent mutant of Cryptococcus neoformans. Mol Microbiol 47, 1007–1014.[CrossRef]
    [Google Scholar]
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