Rapamycin antifungal action is mediated via conserved complexes with FKBP12 and TOR kinase homologs in Cryptococcus neoformans

Molecular and Cellular Biology

Volumn 19, Issue 6, 1999, Pages 4101-4112

  Cruz, M Cristina ^a   Cavallo, Lora M ^a   Görlach, Jenifer M ^a   Cox, Gary ^a   Perfect, John R ^a   Cardenas, Maria E ^a   Heitman, Joseph ^a  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ISOMERASE; PROLINE DERIVATIVE; RAPAMYCIN; TACROLIMUS;

AMINO ACID SEQUENCE; ANTIFUNGAL ACTIVITY; ARTICLE; CRYPTOCOCCUS NEOFORMANS; DNA SEQUENCE; GENE DISRUPTION; GENE ISOLATION; NONHUMAN; NUCLEOTIDE SEQUENCE; OPEN READING FRAME; PHENOTYPE; PRIORITY JOURNAL; SACCHAROMYCES CEREVISIAE; SITE DIRECTED MUTAGENESIS; T LYMPHOCYTE;

EID: 0033043180     PISSN: 02707306     EISSN: None     Source Type: Journal    
DOI: 10.1128/MCB.19.6.4101     Document Type: Article

References (77)

1. Alarcon, C. M., M. E. Cardenas, and J. Heitman. 1996. Mammalian RAFT1 kinase domain provides rapamycin-sensitive TOR function in yeast. Genes Dev. 10:279-288.
2. Alarcon, C. M., and J. Heitman. 1997. FKBP12 physically and functionally interacts with aspartokinase in Saccharomyces cerevisiae. Mol. Cell. Biol. 17:5968-5975.
3. Alspaugh, J. A., J. R. Perfect, and J. Heitman. 1997. Cryptococcus neoformans mating and virulence are regulated by the G-protein α subunit GPA1 and cAMP. Genes Dev. 11:3206-3217.
4. Barbet, N. C., U. Schneider, S. B. Helliwell, I. Stansfield, M. F. Tuite, and M. N. Hall. 1996. TOR controls translation initiation and early G1 progression in yeast. Mol. Biol. Cell 7:25-42.
5. Beretta, L., A.-C. Gingras, Y. V. Svitkin, M. N. Hall, and N. Sonenberg. 1996. Rapamycin blocks the phosphorylation of 4E-BP1 and inhibits cap-dependent initiation of translation. EMBO J. 15:658-664.
6. Berset, C., H. Trachsel, and M. Altmann. 1998. The TOR (target of rapamycin) signal transduction pathway regulates the stability of translation initiation factor eIF4G in the yeast Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 95:4264-4269.
7. Borel, J. F. 1976. Comparative study of in vitro and in vivo drug effects on cell-mediated cytotoxicity. Immunology 31:631-641.
8. Breuder, T., C. S. Hemenway, N. R. Movva, M. E. Cardenas, and J. Heitman. 1994. Calcineurin is essential in cyclosporin A- and FK506-sensitive yeast strains. Proc. Natl. Acad. Sci. USA 91:5372-5376.
9. Brown, E. J., M. W. Albers, T. B. Shin, K. Ichikawa, C. T. Keith, W. S. Lane, and S. L. Schreiber. 1994. A mammalian protein targeted by G1-arresting rapamycin-receptor complex. Nature 369:756-759.
10. Brown, E. J., P. A. Beal, C. T. Keith, J. Chen, T. B. Shin, and S. L. Schreiber. 1995. Control of p70 S6 kinase by kinase activity of FRAP in vivo. Nature 377:441-446.
11. Brown, E. J., and S. L. Schreiber. 1996. A signaling pathway to translational control. Cell 86:517-520.
12. Brunn, G. J., P. Fadden, T. A. J. Haystead, and J. J. C. Lawrence. 1997. The mammalian target of rapamycin phosphorylates sites having a (Ser/Thr)-pro motif and is activated by antibodies to a region near its COOH terminus. J. Biol. Chem. 272:32547-32550.
13. Brunn, G. J., C. C. Hudson, A. Sekulic, J. M. Williams, J. Hosoi, P. J. Houghton, J. J. C. Lawrence, and R. T. Abraham. 1997. Phosphorylation of the translational repressor PHAS-I by the mammalian target of rapamycin. Science 277:99-101.
14. Burnett, P. E., R. K. Barrow, N. A. Cohen, S. H. Snyder, and D. M. Sabatini. 1998. RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1. Proc. Natl. Acad. Sci. USA 95:1432-1437.
15. Cafferkey, R., P. R. Young, M. M. McLaughlin, D. J. Bergsma, Y. Koltin, G. M. Sathe, L. Faucette, W.-K. Eng, R. K. Johnson, and G. P. Livi. 1993. Dominant missense mutations in a novel yeast protein related to mammalian phosphatidylinositol 3-kinase and VPS34 abrogate rapamycin cytotoxicity. Mol. Cell. Biol. 13:6012-6023.
16. Cardenas, M., C. Hemenway, R. S. Muir, R. Ye, D. Fiorentino, and J. Heitman. 1994. Immunophilins interact with calcineurin in the absence of exogenous immunosuppressive ligands. EMBO J. 13:5944-5957.
17. Cardenas, M. E., and J. Heitman. 1995. FKBP12-rapamycin target TOR2 is a vacuolar protein with an associated phosphatidylinositol-4 kinase activity. EMBO J. 14:5892-5907.
18. Cardenas, M. E., M. Lorenz, C. Hemenway, and J. Heitman. 1994. Yeast as model-T cells. Perspect. Drug Discov. Design 2:103-126.
19. Cardenas, M. E., A. Sanfridson, N. S. Cutler, and J. Heitman. 1998. Signal-transduction cascades as targets for therapeutic intervention by natural products. Trends Biotechnol. 16:427-433.
20. Casadevall, A., and J. R. Perfect. 1998. Cryptococcus neoformans. ASM Press, Washington, D.C.
21. Chiu, M. I., H. Katz, and V. Berlin. 1994. RAPT1, a mammalian homolog of yeast Tor, interacts with the FKBP12/rapamycin complex. Proc. Natl. Acad. Sci. USA 91:12574-12578.
22. Choi, J., J. Chen, S. L. Schreiber, and J. Clardy. 1996. Structure of the FKBP12-rapamycin complex interacting with the binding domain of human FRAP. Science 273:239-242.
23. 22a.Cruz, M. C., and J. Heitman. Unpublished data.
24. Di Como, C. J., and K. T. Arndt. 1996. Nutrients, via the Tor proteins, stimulate the association of Tap42 with type 2A phosphatases. Genes Dev. 10:1904-1916.
25. Dolinski, K., and J. Heitman. 1997. Peptidyl-prolyl isomerases (PPIases), p. 359-369. In S. Tooze (ed.), Guidebook to molecular chaperones and protein folding catalysts. Oxford University Press, Oxford, United Kingdom.
26. Ferrara, A., R. Cafferkey, and G. P. Livi. 1992. Cloning and sequence analysis of a rapamycin-binding protein-encoding gene (RBP1) from Candida albicans. Gene 113:125-127.
27. Foor, F., S. A. Parent, N. Morin, A. M. Dahl, N. Ramadan, G. Chrebet, K. A. Bostian, and J. B. Nielsen. 1992. Calcineurin mediates inhibition by FK506 and cydosporin of recovery from α-factor arrest in yeast. Nature 360:682-684.
28. Gimeno, C. J., P. O. Ljungdahl, C. A. Styles, and G. R. Fink. 1992. Unipolar cell divisions in the yeast S. cerevisiae lead to filamentous growth: regulation by starvation and RAS. Cell 68:1077-1090.
29. Gingras, A.-C., S. G. Kennedy, M. A. O'Leary, N. Sonenberg, and N. Hay. 1998. 4E-BP1, a repressor of mRNA translation, is phosphorylated and inactivated by the Akt(PKB) signaling pathway. Genes Dev. 12:502-513.
30. Hall, M. 1996. The TOR signalling pathway and growth control in yeast. Biochem. Soc. Trans. 24:234-239.
31. Hara, K., Yonezawa, M. T. Kozlowski, T. Sugimoto, K. Andrabi, Q.-P. Weng, M. Kasuga, I. Nishimoto, and J. Avruch. 1997. Regulation of eIF-4E BP1 phosphorylation by mTOR. J. Biol. Chem. 272:26457-26463.
32. Heitman, J., A. Koller, M. E. Cardenas, and M. N. Hall. 1993. Identification of immunosuppressive drug targets in yeast. Methods Companion Methods Enzymol. 5:176-187.
33. Heitman, J., N. R. Movva, and M. N. Hall. 1992. Proline isomerases at the crossroads of protein folding, signal transduction, and immunosuppression. New Biol. 4:448-460.
34. Heitman, J., N. R. Movva, and M. N. Hall. 1991. Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast. Science 253:905-909.
35. Heitman, J., N. R. Movva, P. C. Hiestand, and M. N. Hall. 1991. FK506-binding protein proline rotamase is a target for the immunosuppressive agent FK506 in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 88: 1948-1952.
36. Helliwell, S. B., P. Wagner, J. Kunz, M. Deuter-Reinhard, R. Henriquez, and M. N. Hall. 1994. TOR1 and TOR2 are structurally and functionally similar but not identical phosphatidylinositol kinase homologues in yeast. Mol. Biol. Cell 5:105-118.
37. Ho, S. N., H. D. Hunt, R. M. Horton, J. K. Pullen, and L. R. Pease. 1989. Site-directed mutagenesis by overlap extension using the polymerase chain reaction. Gene 77:51-59.
38. James, P., J. Halladay, and E. A. Craig. 1996. Genomic libraries and a host strain designed for highly efficient two-hybrid selection in yeast. Genetics 144:1425-1436.
39. Kino, T., H. Hatanaka, M. Hashimoto, M. Nishiyama, T. Goto, M. Okuhara, M. Kohsaka, H. Aoki, and H. Imanaka. 1987. FK-506, a novel immunosuppressant isolated from a Streptomyces. I. Fermentation, isolation, physicochemical and biological characteristics. J. Antibiot. 40:1249-1255.
40. Koltin, Y., L. Faucette, D. J. Bergsma, M. A. Levy, R. Cafferkey, P. L. Koser, R. K. Johnson, and G. P. Livi. 1991. Rapamycin sensitivity in Saccharomyces cerevisiae is mediated by a peptidyl-prolyl cis-trans isomerase related to human FK506-binding protein. Mol. Cell. Biol. 11:1718-1723.
41. 1 progression. Cell 73: 585-596.
42. Liu, J., J. D. Farmer, W. S. Lane, J. Friedman, I. Weissman, and S. L. Schreiber. 1991. Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes. Cell 66:807-815.
43. Lodge, J. K., E. Jackson-Machelski, D. L. Toffaletti, J. R. Perfect, and J. I. Gordon. 1994. Targeted gene replacement demonstrates that myristoyl-CoA: protein N-myristoyltransferase is essential for viability of Cryptococcus neoformans. Proc. Natl. Acad. Sci. USA 91:12008-12012.
44. Lorenz, M. C., and J. Heitman. 1995. TOR mutations confer rapamycin resistance by preventing interaction with FKBP12-rapamycin. J. Biol. Chem. 270:27531-27537.
45. Matheos, D. P., T. J. Kingsbury, U. S. Ahsan, and K. W. Cunningham. 1997. Tcn1p/Crz1p, a calcineurin-dcpendent transcription factor that differentially regulates gene expression in Saccharomyces cerevisiae. Genes Dev. 11:3445-3458.
46. Mitchell, T. G., and J. R. Perfect. 1995. Cryptococcosis in the era of AIDS -100 years after the discovery of Cryptococcus neoformans. Clin. Microbiol. Rev. 8:515-548.
47. Moore, T. D. E., and J. C. Edman. 1993. The α-mating type locus of Cryptococcus neoformans contains a peptide pheromone gene. Mol. Cell. Biol. 13:1962-1970.
48. Noda, T., and Y. Ohsumi. 1998. Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast. J. Biol. Chem. 273:3963-3966.
49. Odom, A., S. Muir, E. Lim, D. L. Toffaletti, J. Perfect, and J. Heitman. 1997. Calcineurin is required for virulence of Cryptococcus neoformans. EMBO J. 16:2576-2589.
50. Odom, A., M. D. Poeta, J. Perfect, and J. Heitman. 1997. The immunosuppressant FK506 and its nonimmunosuppressive analog L-685,818 are toxic to Cryptococcus neoformans by inhibition of a common target protein. Antimicrob. Agents Chemother. 41:156-161.
51. Perfect, J. R., S. D. R. Lang, and D. T. Durack. 1980. Chronic cryptococcal meningitis: a new experimental model in rabbits. Am. J. Pathol. 101:177-194.
52. Perfect, J. R., D. L. Tofaletti, and T. H. Rude. 1993. The gene encoding phosphoribosylaminoimidazole carboxylase (ADE2) is essential for growth of Cryptococcus neoformans in cerebrospinal fluid. Infect. Immun. 61:4446-4451.
53. Pitkin, J. W., D. G. Panaccione, and J. D. Walton. 1996. A putative cyclic peptide efflux pump encoded by the TOXA gene of the plant-pathogenic fungus Cochliobolus carbonum. Microbiology 142:1557-1565.
54. Rao, A., C. Luo, and P. G. Hogan. 1997. Transcription factors of the NF-AT family: regulation and function. Annu. Rev. Immunol. 15:707-747.
55. 53a.Roe, B., D. Kupfer, J. Lewis, K. Buchanan, D. Dyer, and J. Murphy. 29 September 1998, posting date. Cryptococcus neoformans cDNA sequencing. [Online.] http://www.genome.ou.edu/cneo.html. [19 April 1999, last date accessed.]
56. Sabatini, D. M., H. Erdjument-Bramage, M. Lui, P. Tempst, and S. H. Snyder. 1994. RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs. Cell 78: 35-43.
57. Sabers, C. J., M. M. Martin. G. J. Brunn, J. M. Williams, F. J. Dumont, G. Wiederrecht, and R. T. Abraham. 1995. Isolation of a protein target of the FKBP12-rapamycin complex in mammalian cells. J. Biol. Chem. 270:815-822.
58. Schmid, F. X. 1993. Prolyl isomerase - enzymatic catalysis of slow protein-folding reactions. Annu. Rev. Biophys. Biomol. Struct. 22:123-143.
59. Schmidt, A., M. Bickle, T. Beck, and M. N. Hall. 1997. The yeast phosphatidylinositol kinase homolog TOR2 activates RHO1 and RHO2 via the exchange factor ROM2. Cell 88:531-542.
60. Schmidt, A., J. Kunz, and M. N. Hall. 1996. TOR2 is required for organization of the actin cytoskeleton in yeast. Proc. Natl. Acad. Sci. USA 93: 13780-13785.
61. Schreiber, S. L., and G. R. Crabtree. 1992. The mechanism of action of cyclosporin A and FK506. Immunol. Today 13:136-142.
62. Scott, P. H., G. J. Brunn, A. D. Kohn, R. A. Roth, and J. C. Lawrence. 1998. Evidence of insulin-stimulated phosphorylation and activation of the mammalian target of rapamycin mediated by a protein kinase B signaling pathway. Proc. Natl. Acad. Sci. USA 95:7772-7777.
63. Sherman, F. 1991. Getting started with yeast. Methods Enzymol. 194:3-21.
64. Singh, K., S. Sun, and C. Vezina. 1979. Rapamycin (AY-22,989), a new antifungal antibiotic. IV. Mechanism of action. J. Antibiot. 32:630-645.
65. Stan, R., M. M. McLaughlin, R. T. Cafferkey, R. K. Johnson, M. Rosenberg, and G. P. Livi. 1994. Interaction between FKBP12-rapamycin and TOR involves a conserved serine residue. J. Biol. Chem. 269:32027-32030.
66. Standaert, R. F., A. Galat, G. L. Verdine, and S. L. Schreiber. 1990. Molecular cloning and overexpression of the human FK506-binding protein FKBP. Nature 346:671-674.
67. Stathopoulos, A. M., and M. S. Cyert. 1997. Calcineurin acts through the CRZ1/TCN1-encoded transcription factor to regulate gene expression in yeast. Genes Dev. 11:3432-3444.
68. Thomas, G., and M. N. Hall. 1997. TOR signalling and control of cell growth. Curr. Opin. Cell Biol. 9:782-787.
69. Toffaletti, D. L., T. H. Rude, S. A. Johnston, D. T. Durack, and J. R. Perfect. 1993. Gene transfer in Cryptococcus neoformans by use of biolistic delivery of DNA. J. Bacteriol. 175:1405-1411.
70. Tropschug, M., E. Wachter, S. Mayer, E. R. Schonbrunner, and F. X. Schmid. 1990. Isolation and sequence of an FK506-binding protein from N. crassa which catalyses protein folding. Nature 346:674-677.
71. Van Duyne, G. D., R. F. Standaert, P. A. Karplus, S. L. Schreiber, and J. Clardy. 1991. Atomic structure of FKBP-FK506, an immunophilin-immunosuppressant complex. Science 252:839-842.
72. Van Duyne, G. D., R. F. Standaert, P. A. Karplus, S. L. Schreiber, and J. Clardy. 1993. Atomic structures of the human immunophilin FKBP-12 complexes with FK506 and rapamycin. J. Mol. Biol. 229:105-124.
73. Vartivarian, S. E., E. J. Anaissie, R. E. Cowart, H. A. Sprigg, M. J. Tingler, and E. S. Jacobson. 1993. Regulation of cryptococcal capsular polysaccharide by iron. J. Infect. Dis. 167:186-190.
74. Weisman, R., M. Choder, and Y. Koltin. 1997. Rapamycin specifically interferes with the developmental response of fission yeast to starvation. J. Bacteriol. 179:6325-6334.
75. Wong, G. K., S. Griffith, I. Kojima, and A. L. Demain. 1998. Antifungal activities of rapamycin and its derivatives, prolylrapamycin, 32-desmethylrapamycin, and 32-desmethoxyrapamycin. J. Antibiot. 51:487-491.
76. Zheng, X.-F., D. Fiorentino, J. Chen, G. R. Crabtree, and S. L. Schreiber. 1995. TOR kinase domains are required for two distinct functions, only one of which is inhibited by rapamycin. Cell 82:121-130.
77. Zheng, X. F., and S. L. Schreiber. 1997. Target of rapamycin proteins and their kinase activities are required for meiosis. Proc. Natl. Acad. Sci. USA 94:3070-3075.