Calcineurin-Crz1 signaling in lower eukaryotes

Eukaryotic Cell

Volumn 13, Issue 6, 2014, Pages 694-705

  Thewes, S ^a  

^a FREIE UNIVERSITÄT BERLIN   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CALCINEURIN; CRZ1 PROTEIN, S CEREVISIAE; DNA BINDING PROTEIN; PROTOZOAL PROTEIN; SACCHAROMYCES CEREVISIAE PROTEIN; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR NFAT;

AMOEBOZOA; CALCIUM SIGNALING; GENETICS; METABOLISM; YEAST;

AMOEBOZOA; CALCINEURIN; CALCIUM SIGNALING; DNA-BINDING PROTEINS; NFATC TRANSCRIPTION FACTORS; PROTOZOAN PROTEINS; SACCHAROMYCES CEREVISIAE PROTEINS; TRANSCRIPTION FACTORS; YEASTS;

EID: 84901456605     PISSN: 15359778     EISSN: None     Source Type: Journal    
DOI: 10.1128/EC.00038-14     Document Type: Review

References (120)

1. Rusnak F, Mertz P. 2000. Calcineurin: form and function. Physiol. Rev. 80: 1483-1521.
2. Cyert MS. 2003. Calcineurin signaling in Saccharomyces cerevisiae: how yeast go crazy in response to stress. Biochem. Biophys. Res. Commun. 311: 1143-1150. http://dx.doi.org/10.1016/S0006-291X(03)01552-3.
3. Chen Y-L, Kozubowski L, Cardenas ME, Heitman J. 2010. On the roles of calcineurin in fungal growth and pathogenesis. Curr. Fungal Infect. Rep. 4: 244-255. http://dx.doi.org/10.1007/s12281-010-0027-5.
4. Boeckeler K, Tischendorf G, Mutzel R, Weissenmayer B. 2006. Aberrant stalk development and breakdown of tip dominance in Dictyostelium cell lines with RNAi-silenced expression of calcineurin B. BMCDev. Biol. 6: 12. http://dx.doi.org/10.1186/1471-213X-6-12.
5. Thewes S, Schubert SK, Park K, Mutzel R. 20 May 2013. Stress and development in Dictyostelium discoideum: the involvement of the catalytic calcineurin A subunit. J. Basic Microbiol. http://dx.doi.org/10.1002/jobm.201200574.
6. Kumar R, Musiyenko A, Oldenburg A, Adams B, Barik S. 2004. Posttranslational generation of constitutively active cores from larger phosphatases in the malaria parasite, Plasmodium falciparum: implications for proteomics. BMCMol. Biol. 5: 6. http://dx.doi.org/10.1186/1471-2199-5-6.
7. Moreno VR, Agüero F, Tekiel V, Sánchez DO. 2007. The calcineurin A homologue from Trypanosoma cruzi lacks two important regulatory domains. Acta Trop. 101: 80-89. http://dx.doi.org/10.1016/j.actatropica.2006.11.008.
8. Araya JE, Cornejo A, Orrego PR, Cordero EM, Cortéz M, Olivares H, Neira I, Sagua H, da Silveira JF, Yoshida N, González J. 2008. Calcineurin B of the human protozoan parasite Trypanosoma cruzi is involved in cell invasion. Microbes Infect. 10: 892-900. http://dx.doi.org/10.1016/j.micinf.2008.05.003.
9. Montenegro M, Cardenas C, Cuervo C, Bernal C, Grisard EC, Thomas MC, Lopez MC, Puerta CJ. 2013. Molecular characterization of calcineurin B from the non-virulent Trypanosoma rangeli kinetoplastid indicates high gene conservation. Mol. Biol. Rep. 40: 4901-4912. http://dx.doi.org/10.1007/s11033-013-2590-7.
10. Mecozzi B, Rossi A, Lazzaretti P, Kady M, Kaiser S, Valle C, Cioli D, Klinkert MQ. 2000. Molecular cloning of Schistosoma mansoni calcineurin subunits and immunolocalization to the excretory system. Mol. Biochem. Parasitol. 110: 333-343. http://dx.doi.org/10.1016/S0166-6851(00)00287-5.
11. Naderer T, Dandash O, McConville MJ. 2011. Calcineurin is required for Leishmania major stress response pathways and for virulence in the mammalian host. Mol. Microbiol. 80: 471-480. http://dx.doi.org/10.1111/j.1365-2958.2011.07584.x.
12. Fraga D, Sehring IM, Kissmehl R, Reiss M, Gaines R, Hinrichsen R, Plattner H. 2010. Protein phosphatase 2B (PP2B, calcineurin) in Paramecium: partial characterization reveals that two members of the unusually large catalytic subunit family have distinct roles in calciumdependent processes. Eukaryot. Cell 9: 1049-1063. http://dx.doi.org/10.1128/EC.00322-09.
13. Li H, Rao A, Hogan PG. 2011. Interaction of calcineurin with substrates and targeting proteins. Trends Cell Biol. 21: 91-103. http://dx.doi.org/10.1016/j.tcb.2010.09.011.
14. Stathopoulos AM, Cyert MS. 1997. Calcineurin acts through the CRZ1/ TCN1-encoded transcription factor to regulate gene expression in yeast. Genes Dev. 11: 3432-3444. http://dx.doi.org/10.1101/gad.11.24.3432.
15. Hirayama S, Sugiura R, Lu Y, Maeda T, Kawagishi K, Yokoyama M, Tohda H, Giga-Hama Y, Shuntoh H, Kuno T. 2003. Zinc finger protein Prz1 regulates Ca2+butnotCl-homeostasisinfissionyeast. Identification of distinctbranches of calcineurin signaling pathway in fission yeast. J. Biol. Chem. 278: 18078-18084. http://dx.doi.org/10.1074/jbc.M212900200.
16. Soriani FM, Malavazi I, da Silva Ferreira ME, Savoldi M, Von Zeska Kress MR, de Souza Goldman MH, Loss O, Bignell E, Goldman GH. 2008. Functional characterization of the Aspergillus fumigatus CRZ1 homologue, CrzA. Mol. Microbiol. 67: 1274-1291. http://dx.doi.org/10.1111/j.1365-2958.2008.06122.x.
17. Spielvogel A, Findon H, Arst HN, Araujo-Bazan L, Hernandez-Ortiz P, Stahl U, Meyer V, Espeso EA. 2008. Two zinc finger transcription factors, CrzA and SltA, are involved in cation homoeostasis and detoxification in Aspergillus nidulans. Biochem. J. 414: 419-429. http://dx.doi.org/10.1042/BJ20080344.
18. Cramer RA, Jr, Perfect BZ, Pinchai N, Park S, Perlin DS, Asfaw YG, Heitman J, Perfect JR, Steinbach WJ. 2008. Calcineurin target CrzA regulates conidial germination, hyphal growth, and pathogenesis of Aspergillus fumigatus. Eukaryot. Cell 7: 1085-1097. http://dx.doi.org/10.1128/EC.00086-08.
19. Thewes S, Krohn S, Schmith A, Herzog S, Stach T, Weissenmayer B, Mutzel R. 2012. The calcineurin dependent transcription factor TacA is involved in development and the stress response of Dictyostelium discoideum. Eur. J. Cell Biol. 91: 789-799. http://dx.doi.org/10.1016/j.ejcb.2012.07.006.
20. Santos M, de Larrinoa IF. 2005. Functional characterization of the Candida albicans CRZ1 gene encoding a calcineurin-regulated transcription factor. Curr. Genet. 48: 88-100. http://dx.doi.org/10.1007/s00294-005-0003-8.
21. Hernandez-Lopez MJ, Panadero J, Prieto JA, Randez-Gil F. 2006. Regulation of salt tolerance by Torulaspora delbrueckii calcineurin target Crz1p. Eukaryot. Cell 5: 469-479. http://dx.doi.org/10.1128/EC.5.3.469-479.2006.
22. Karababa M, Valentino E, Pardini G, Coste AT, Bille J, Sanglard D. 2006. CRZ1, a target of the calcineurin pathway in Candida albicans. Mol. Microbiol. 59: 1429-1451. http://dx.doi.org/10.1111/j.1365-2958.2005.05037.x.
23. Schumacher J, de Larrinoa IF, Tudzynski B. 2008. Calcineurinresponsive zinc finger transcription factor CRZ1 of Botrytis cinerea is required for growth, development, and full virulence on bean plants. Eukaryot. Cell 7: 584-601. http://dx.doi.org/10.1128/EC.00426-07.
24. Hagiwara D, Kondo A, Fujioka T, Abe K. 2008. Functional analysis of C2H2 zinc finger transcription factor CrzA involved in calcium signaling in Aspergillus nidulans. Curr. Genet. 54: 325-338. http://dx.doi.org/10.1007/s00294-008-0220-z.
25. Chang PK. 2008. Aspergillus parasiticus crzA, which encodes calcineurin response zinc-finger protein, is required for aflatoxin production under calcium stress. Int. J. Mol. Sci. 9: 2027-2043. http://dx.doi.org/10.3390/ijms9102027.
26. Zhang H, Zhao Q, Liu K, Zhang Z, Wang Y, Zheng X. 2009. MgCRZ1, a transcription factor of Magnaporthe grisea, controls growth, development and is involved in full virulence. FEMS Microbiol. Lett. 293: 160-169. http://dx.doi.org/10.1111/j.1574-6968.2009.01524.x.
27. Choi J, Kim Y, Kim S, Park J, Lee YH. 2009. MoCRZ1, a gene encoding a calcineurin-responsive transcription factor, regulates fungal growth and pathogenicity of Magnaporthe oryzae. Fungal Genet. Biol. 46: 243-254. http://dx.doi.org/10.1016/j.fgb.2008.11.010.
28. Miyazaki T, Yamauchi S, Inamine T, Nagayoshi Y, Saijo T, Izumikawa K, Seki M, Kakeya H, Yamamoto Y, Yanagihara K, Miyazaki Y, Kohno S. 2010. Roles of calcineurin and Crz1 in antifungal susceptibility and virulence of Candida glabrata. Antimicrob. Agents Chemother. 54: 1639-1643. http://dx.doi.org/10.1128/AAC.01364-09.
29. Reedy JL, Filler SG, Heitman J. 2010. Elucidating the Candida albicans calcineurin signaling cascade controlling stress response and virulence. Fungal Genet. Biol. 47: 107-116. http://dx.doi.org/10.1016/j.fgb.2009.09.002.
30. Araki Y, Wu H, Kitagaki H, Akao T, Takagi H, Shimoi H. 2009. Ethanol stress stimulates the Ca2+-mediated calcineurin/Crz1 pathway in Saccharomyces cerevisiae. J. Biosci. Bioeng. 107: 1-6. http://dx.doi.org/10.1016/j.jbiosc.2008.09.005.
31. Calvo IA, Gabrielli N, Iglesias-Baena I, García-Santamarina S, Hoe KL, Kim DU, Sansó M, Zuin A, Pérez P, Ayté J, Hidalgo E. 2009. Genome-wide screen of genes required for caffeine tolerance in fission yeast. PLoS One 4: e6619. http://dx.doi.org/10.1371/journal.pone.0006619.
32. Chen YL, Konieczka JH, Springer DJ, Bowen SE, Zhang J, Silao FG, Bungay AA, Bigol UG, Nicolas MG, Abraham SN, Thompson DA, Regev A, Heitman J. 2012. Convergent evolution of calcineurin pathway roles in thermotolerance and virulence in Candida glabrata. G3 (Bethesda) 2: 675-691. http://dx.doi.org/10.1534/g3.112.002279.
33. Ruiz A, Serrano R, Arino J. 2008. Direct regulation of genes involved in glucose utilization by the calcium/calcineurin pathway. J. Biol. Chem. 283: 13923-13933. http://dx.doi.org/10.1074/jbc.M708683200.
34. Bodvard K, Jörhov Blomberg AA, Molin M, Käll M. 2013. The yeast transcription factor Crz1 is activated by light in a Ca2+/calcineurindependent and PKA-independent manner. PLoS One 8: e53404. http://dx.doi.org/10.1371/journal.pone.0053404.
35. Rodríguez C, Galindo LR, Siverio JM. 9 February 2013. Nitrogendependent calcineurin activation in the yeast Hansenula polymorpha. Fungal Genet. Biol. http://dx.doi.org/10.1016/j.fgb.2013.01.007.
36. Edlind T, Smith L, Henry K, Katiyar S, Nickels J. 2002. Antifungal activity in Saccharomyces cerevisiae is modulated by calcium signalling. Mol. Microbiol. 46: 257-268. http://dx.doi.org/10.1046/j.1365-2958.2002.03165.x.
37. Polizotto RS, Cyert MS. 2001. Calcineurin-dependent nuclear import of the transcription factor Crz1p requires Nmd5p. J. Cell Biol. 154: 951-960. http://dx.doi.org/10.1083/jcb.200104078.
38. Boustany LM, Cyert MS. 2002. Calcineurin-dependent regulation of Crz1p nuclear export requires Msn5p and a conserved calcineurin docking site. Genes Dev. 16: 608-619. http://dx.doi.org/10.1101/gad.967602.
39. Koike A, Kato T, Sugiura R, Ma Y, Tabata Y, Ohmoto K, Sio SO, Kuno T. 2012. Genetic screening for regulators of Prz1, a transcriptional factor acting downstream of calcineurin in fission yeast. J. Biol. Chem. 287: 19294-19303. http://dx.doi.org/10.1074/jbc.M111.310615.
40. Cai L, Dalal CK, Elowitz MB. 2008. Frequency-modulated nuclear localization bursts coordinate gene regulation. Nature 455: 485-490. http://dx.doi.org/10.1038/nature07292.
41. Kwon OY, Kwon IC, Song HK, Jeon H. 2008. Real-time imaging of NF-AT nucleocytoplasmic shuttling with a photoswitchable fluorescence protein in live cells. Biochim. Biophys. Acta 1780: 1403-1407. http://dx.doi.org/10.1016/j.bbagen.2008.08.003.
42. Nelson G, Kozlova-Zwinderman O, Collis AJ, Knight MR, Fincham JR, Stanger CP, Renwick A, Hessing JG, Punt PJ, van den Hondel CA, Read ND. 2004. Calcium measurement in living filamentous fungi expressing codon-optimized aequorin. Mol. Microbiol. 52: 1437-1450. http://dx.doi.org/10.1111/j.1365-2958.2004.04066.x.
43. Kim HS, Czymmek KJ, Patel A, Modla S, Nohe A, Duncan R, Gilroy S, Kang S. 2012. Expression of the Cameleon calcium biosensor in fungi reveals distinct Ca(2+) signatures associated with polarized growth, development, and pathogenesis. Fungal Genet. Biol. 49: 589-601. http://dx.doi.org/10.1016/j.fgb.2012.05.011.
44. Bumann J, Malchow D, Wurster B. 1986. Oscillations of Ca++concentration during the cell differentiation of Dictyostelium discoideum: their relation to oscillations in cyclic AMP and other components. Differentiation 31: 85-91. http://dx.doi.org/10.1111/j.1432-0436.1986.tb00387.x.
45. Smedler E, Uhlén P. 2014. Frequency decoding of calcium oscillations. Biochim. Biophys. Acta1840: 964-969. http://dx.doi.org/10.1016/j.bbagen.2013.11.015.
46. Kafadar KA, Cyert MS. 2004. Integration of stress responses: modulation of calcineurin signaling in Saccharomyces cerevisiae by protein kinase A. Eukaryot. Cell 3: 1147-1153. http://dx.doi.org/10.1128/EC.3.5.1147-1153.2004.
47. Williams KE, Cyert MS. 2001. The eukaryotic response regulator Skn7p regulates calcineurin signaling through stabilization of Crz1p. EMBO J. 20: 3473-3483. http://dx.doi.org/10.1093/emboj/20.13.3473.
48. Zhu J, Shibasaki F, Price R, Guillemot JC, Yano T, Dötsch V, Wagner G, Ferrara P, McKeon F. 1998. Intramolecular masking of nuclear import signal on NF-AT4 by casein kinase I and MEKK1. Cell 93: 851-861. http://dx.doi.org/10.1016/S0092-8674(00)81445-2.
49. Beals CR, Sheridan CM, Turck CW, Gardner P, Crabtree GR. 1997. Nuclear export of NF-ATc enhanced by glycogen synthase kinase-3. Science 275: 1930-1934. http://dx.doi.org/10.1126/science.275.5308.1930.
50. Gwack Y, Sharma S, Nardone J, Tanasa B, Iuga A, Srikanth S, Okamura H, Bolton D, Feske S, Hogan PG, Rao A. 2006. A genome-wide Drosophila RNAi screen identifies DYRK-family kinases as regulators of NFAT. Nature 441: 646-650. http://dx.doi.org/10.1038/nature04631.
51. Gómez del Arco P, Martínez-Martínez S, Maldonado JL, Ortega-Pérez I, Redondo JM. 2000. A role for the p38 MAP kinase pathway in the nuclear shuttling of NFATp. J. Biol. Chem. 275: 13872-13878. http://dx.doi.org/10.1074/jbc.275.18.13872.
52. Chow CW, Rincón M, Cavanagh J, Dickens M, Davis RJ. 1997. Nuclear accumulation of NFAT4 opposed by the JNK signal transduction pathway. Science 278: 1638-1641. http://dx.doi.org/10.1126/science.278.5343.1638.
53. Kafadar KA, Zhu H, Snyder M, Cyert MS. 2003. Negative regulation of calcineurin signaling by Hrr25p, a yeast homolog of casein kinase I. Genes Dev. 17: 2698-2708. http://dx.doi.org/10.1101/gad.1140603.
54. Hernández-Ortiz P, Espeso EA. 2013. Phospho-regulation and nucleocytoplasmic trafficking of CrzA in response to calcium and alkaline-pH stress in Aspergillus nidulans. Mol. Microbiol. 89: 532-551. http://dx.doi.org/10.1111/mmi.12294.
55. Yoshimoto H, Saltsman K, Gasch AP, Li HX, Ogawa N, Botstein D, Brown PO, Cyert MS. 2002. Genome-wide analysis of gene expression regulated by the calcineurin/Crz1p signaling pathway in Saccharomyces cerevisiae. J. Biol. Chem. 277: 31079-31088. http://dx.doi.org/10.1074/jbc.M202718200.
56. Hogan PG, Chen L, Nardone J, Rao A. 2003. Transcriptional regulation by calcium, calcineurin, and NFAT. Genes Dev. 17: 2205-2232. http://dx.doi.org/10.1101/gad.1102703.
57. Crabtree GR, Olson EN. 2002. NFAT signaling: choreographing the social lives of cells. Cell 109(Suppl): S67-S79. http://dx.doi.org/10.1016/S0092-8674(02)00699-2.
58. Macián F, García-Rodríguez C, Rao A. 2000. Gene expression elicited by NFAT in the presence or absence of cooperative recruitment of Fos and Jun. EMBO J. 19: 4783-4795. http://dx.doi.org/10.1093/emboj/19.17.4783.
59. Emes RD, Ponting CP. 2001. A new sequence motif linking lissencephaly, Treacher Collins and oral-facial-digital type 1 syndromes, microtubule dynamics and cell migration. Hum. Mol. Genet. 10: 2813-2820. http://dx.doi.org/10.1093/hmg/10.24.2813.
60. Adler A, Park YD, Larsen P, Nagarajan V, Wollenberg K, Qiu J, Myers TG, Williamson PR. 2011. A novel specificity protein 1 (SP1)-like gene regulating protein kinase C-1 (Pkc1)-dependent cell wall integrity and virulence factors in Cryptococcus neoformans. J. Biol. Chem. 286: 20977-20990. http://dx.doi.org/10.1074/jbc.M111.230268.
61. Soriani FM, Malavazi I, Savoldi M, Espeso E, Dinamarco TM, Bernardes LA, Ferreira ME, Goldman MH, Goldman GH. 2010. Identification of possible targets of the Aspergillus fumigatus CRZ1 homologue, CrzA. BMC Microbiol. 10: 12. http://dx.doi.org/10.1186/1471-2180-10-12.
62. Fortwendel JR, Juvvadi PR, Perfect BZ, Rogg LE, Perfect JR, Steinbach WJ. 2010. Transcriptional regulation of chitin synthases by calcineurin controls paradoxical growth of Aspergillus fumigatus in response to caspofungin. Antimicrob. Agents Chemother. 54: 1555-1563. http://dx.doi.org/10.1128/AAC.00854-09.
63. Kim S, Hu J, Oh Y, Park J, Choi J, Lee YH, Dean RA, Mitchell TK. 2010. Combining ChIP-chip and expression profiling to model the MoCRZ1 mediated circuit for Ca/calcineurin signaling in the rice blast fungus. PLoS Pathog. 6: e1000909. http://dx.doi.org/10.1371/journal.ppat.1000909.
64. Lev S, Desmarini D, Chayakulkeeree M, Sorrell TC, Djordjevic JT. 2012. The Crz1/Sp1 transcription factor of Cryptococcus neoformans is activated by calcineurin and regulates cell wall integrity. PLoS One 7: e51403. http://dx.doi.org/10.1371/journal.pone.0051403.
65. Chen YL, Brand A, Morrison EL, Silao FG, Bigol UG, Malbas FF, Nett JE, Andes DR, Solis NV, Filler SG, Averette A, Heitman J. 2011. Calcineurin controls drug tolerance, hyphal growth, and virulence in Candida dubliniensis. Eukaryot. Cell 10: 803-819. http://dx.doi.org/10.1128/EC.00310-10.
66. Zhang J, Silao FG, Bigol UG, Bungay AA, Nicolas MG, Heitman J, Chen YL. 2012. Calcineurin is required for pseudohyphal growth, virulence, and drug resistance in Candida lusitaniae. PLoS One 7: e44192. http://dx.doi.org/10.1371/journal.pone.0044192.
67. Zhang T, Xu Q, Sun X, Li H. 2013. The calcineurin-responsive transcription factor Crz1 is required for conidation, full virulence and DMI resistance in Penicillium digitatum. Microbiol. Res. 168: 211-222. http://dx.doi.org/10.1016/j.micres.2012.11.006.
68. Moranova Z, Virtudazo E, Hricova K, Ohkusu M, Kawamoto S, Husickova V, Raclavsky V. 22 April 2013. The CRZ1/SP1-like gene links survival under limited aeration, cell integrity and biofilm formation in the pathogenic yeast Cryptococcus neoformans. Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Repub. http://dx.doi.org/10.5507/bp.2013.024.
69. Onyewu C, Wormley FL, Jr, Perfect JR, Heitman J. 2004. The calcineurin target, Crz1, functions in azole tolerance but is not required for virulence of Candida albicans. Infect. Immun. 72: 7330-7333. http://dx.doi.org/10.1128/IAI.72.12.7330-7333.2004.
70. Matheos DP, Kingsbury TJ, Ahsan US, Cunningham KW. 1997. Tcn1p/Crz1p, a calcineurin-dependent transcription factor that differentially regulates gene expression in Saccharomyces cerevisiae. Genes Dev. 11: 3445-3458. http://dx.doi.org/10.1101/gad.11.24.3445.
71. Bader T, Schröppel K, Bentink S, Agabian N, Köhler G, Morschhäuser J. 2006. Role of calcineurin in stress resistance, morphogenesis, and virulence of a Candida albicans wild-type strain. Infect. Immun. 74: 4366-4369. http://dx.doi.org/10.1128/IAI.00142-06.
72. Brand A, Shanks S, Duncan VM, Yang M, Mackenzie K, Gow NA. 2007. Hyphal orientation of Candida albicans is regulated by a calciumdependent mechanism. Curr. Biol. 17: 347-352. http://dx.doi.org/10.1016/j.cub.2006.12.043.
73. Steinbach WJ, Cramer RA, Perfect BZ, Asfaw YG, Sauer TC, Najvar LK, Kirkpatrick WR, Patterson TF, Benjamin DK, Heitman J, Perfect JR. 2006. Calcineurin controls growth, morphology, and pathogenicity in Aspergillus fumigatus. Eukaryot. Cell 5: 1091-1103. http://dx.doi.org/10.1128/EC.00139-06.
74. Bruno VM, Mitchell AP. 2005. Regulation of azole drug susceptibility by Candida albicans protein kinase CK2. Mol. Microbiol. 56: 559-573. http://dx.doi.org/10.1111/j.1365-2958.2005.04562.x.
75. Cowen LE, Carpenter AE, Matangkasombut O, Fink GR, Lindquist S. 2006. Genetic architecture of Hsp90-dependent drug resistance. Eukaryot. Cell 5: 2184-2188. http://dx.doi.org/10.1128/EC.00274-06.
76. Chandra J, Zhou G, Ghannoum MA. 2005. Fungal biofilms and antimycotics. Curr. Drug Targets 6: 887-894. http://dx.doi.org/10.2174/138945005774912762.
77. Juvvadi PR, Gehrke C, Fortwendel JR, Lamoth F, Soderblom EJ, Cook EC, Hast MA, Asfaw YG, Moseley MA, Creamer TP, Steinbach WJ. 2013. Phosphorylation of calcineurin at a novel serine-proline rich region orchestrates hyphal growth and virulence in Aspergillus fumigatus. PLoS Pathog. 9: e1003564. http://dx.doi.org/10.1371/journal.ppat.1003564.
78. Imai J, Yahara I. 2000. Role of HSP90 in salt stress tolerance via stabilization and regulation of calcineurin. Mol. Cell. Biol. 20: 9262-9270. http://dx.doi.org/10.1128/MCB.20.24.9262-9270.2000.
79. Kumar R, Musiyenko A, Barik S. 2005. Plasmodium falciparum calcineurin and its association with heat shock protein 90: mechanisms for the antimalarial activity of cyclosporinAand synergism with geldanamycin. Mol. Biochem. Parasitol. 141: 29-37. http://dx.doi.org/10.1016/j.molbiopara.2005.01.012.
80. Cowen LE, Lindquist S. 2005. Hsp90 potentiates the rapid evolution of new traits: drug resistance in diverse fungi. Science 309: 2185-2189. http://dx.doi.org/10.1126/science.1118370.
81. Singh SD, Robbins N, Zaas AK, Schell WA, Perfect JR, Cowen LE. 2009. Hsp90 governs echinocandin resistance in the pathogenic yeast Candida albicans via calcineurin. PLoS Pathog. 5: e1000532. http://dx.doi.org/10.1371/journal.ppat.1000532.
82. Cowen LE, Singh SD, Köhler JR, Collins C, Zaas AK, Schell WA, Aziz H, Mylonakis E, Perfect JR, Whitesell L, Lindquist S. 2009. Harnessing Hsp90 function as a powerful, broadly effective therapeutic strategy for fungal infectious disease. Proc. Natl. Acad. Sci. U. S. A. 106: 2818-2823. http://dx.doi.org/10.1073/pnas.0813394106.
83. Leach MD, Klipp E, Cowen LE, Brown AJ. 2012. Fungal Hsp90: a biological transistor that tunes cellular outputs to thermal inputs. Nat. Rev. Microbiol. 10: 693-704. http://dx.doi.org/10.1038/nrmicro2875.
84. Serrano R, Ruiz A, Bernal D, Chambers JR, Ariño J. 2002. The transcriptional response to alkaline pH in Saccharomyces cerevisiae: evidence for calcium-mediated signalling. Mol. Microbiol. 46: 1319-1333. http://dx.doi.org/10.1046/j.1365-2958.2002.03246.x.
85. Kullas AL, Martin SJ, Davis D. 2007. Adaptation to environmental pH: integrating the Rim101 and calcineurin signal transduction pathways. Mol. Microbiol. 66: 858-871. http://dx.doi.org/10.1111/j.1365-2958.2007.05929.x.
86. Wang H, Liang Y, Zhang B, Zheng W, Xing L, Li M. 2011. Alkaline stress triggers an immediate calcium fluctuation in Candida albicans mediated by Rim101p and Crz1p transcription factors. FEMS Yeast Res. 11: 430-439. http://dx.doi.org/10.1111/j.1567-1364.2011.00730.x.
87. Meyer V, Spielvogel A, Funk L, Tilburn J, Arst HN, Stahl U. 2005. Alkaline pH-induced up-regulation of the afp gene encoding the antifungal protein (AFP) of Aspergillus giganteus is not mediated by the transcription factor PacC: possible involvement of calcineurin. Mol. Genet. Genomics 274: 295-306. http://dx.doi.org/10.1007/s00438-005-0002-y.
88. Gustin MC, Albertyn J, Alexander M, Davenport K. 1998. MAP kinase pathways in the yeast Saccharomyces cerevisiae. Microbiol. Mol. Biol. Rev. 62: 1264-1300.
89. Shitamukai A, Hirata D, Sonobe S, Miyakawa T. 2004. Evidence for antagonistic regulation of cell growth by the calcineurin and high osmolarity glycerol pathways in Saccharomyces cerevisiae. J. Biol. Chem. 279: 3651-3661. http://dx.doi.org/10.1074/jbc.M306098200.
90. Maeta K, Izawa S, Inoue Y. 2005. Methylglyoxal, a metabolite derived from glycolysis, functions as a signal initiator of the high osmolarity glycerol-mitogen-activated protein kinase cascade and calcineurin/ Crz1-mediated pathway in Saccharomyces cerevisiae. J. Biol. Chem. 280: 253-260. http://dx.doi.org/10.1074/jbc.M408061200.
91. Fuchs BB, Mylonakis E. 2009. Our paths might cross: the role of the fungal cell wall integrity pathway in stress response and cross talk with other stress response pathways. Eukaryot. Cell 8: 1616-1625. http://dx.doi.org/10.1128/EC.00193-09.
92. Levin DE. 2011. Regulation of cell wall biogenesis in Saccharomyces cerevisiae: the cell wall integrity signaling pathway. Genetics 189: 1145-1175. http://dx.doi.org/10.1534/genetics.111.128264.
93. Zhao C, Jung US, Garrett-Engele P, Roe T, Cyert MS, Levin DE. 1998. Temperature-induced expression of yeast FKS2 is under the dual control of protein kinase C and calcineurin. Mol. Cell. Biol. 18: 1013-1022.
94. Wang X, Sheff MA, Simpson DM, Elion EA. 2011. Ste11p MEKK signals through HOG, mating, calcineurin and PKC pathways to regulate the FKS2 gene. BMC Mol. Biol. 12: 51. http://dx.doi.org/10.1186/1471-2199-12-51.
95. Schumacher J, Viaud M, Simon A, Tudzynski B. 2008. The Galpha subunit BCG1, the phospholipase C (BcPLC1) and the calcineurin phosphatase co-ordinately regulate gene expression in the grey mould fungus Botrytis cinerea. Mol. Microbiol. 67: 1027-1050. http://dx.doi.org/10.1111/j.1365-2958.2008.06105.x.
96. Lev S, Desmarini D, Li C, Chayakulkeeree M, Traven A, Sorrell TC, Djordjevic JT. 2013. Phospholipase C of Cryptococcus neoformans regulates homeostasis and virulence by providing inositol trisphosphate as a substrate for Arg1 kinase. Infect. Immun. 81: 1245-1255. http://dx.doi.org/10.1128/IAI.01421-12.
97. Remillard SP, Lai EY, Levy YY, Fulton C. 1995. A calcineurin-Bencoding gene expressed during differentiation of the amoeboflagellate Naegleria gruberi contains two introns. Gene 154: 39-45. http://dx.doi.org/10.1016/0378-1119(94)00860-U.
98. Keyser P, Borge-Renberg K, Hultmark D. 2007. The Drosophila NFAT homolog is involved in salt stress tolerance. Insect Biochem. Mol. Biol. 37: 356-362. http://dx.doi.org/10.1016/j.ibmb.2006.12.009.
99. Müller MR, Rao A. 2010. NFAT, immunity and cancer: a transcription factor comes of age. Nat. Rev. Immunol. 10: 645-656. http://dx.doi.org/10.1038/nri2818.
100. Nilsson LM, Nilsson-Ohman J, Zetterqvist AV, Gomez MF. 2008. Nuclear factor of activated T-cells transcription factors in the vasculature: the good guys or the bad guys? Curr. Opin. Lipidol. 19: 483-490. http://dx.doi.org/10.1097/MOL.0b013e32830dd545.
101. Moore DL, Goldberg JL. 2011. Multiple transcription factor families regulate axon growth and regeneration. Dev. Neurobiol. 71: 1186-1211. http://dx.doi.org/10.1002/dneu.20934.
102. Miyakawa H, Woo SK, Chen CP, Dahl SC, Handler JS, Kwon HM. 1998. Cis-and trans-acting factors regulating transcription of the BGT1 gene in response to hypertonicity. Am. J. Physiol. 274: F753-F761.
103. Miyakawa H, Woo SK, Dahl SC, Handler JS, Kwon HM. 1999. Tonicity-responsive enhancer binding protein, a rel-like protein that stimulates transcription in response to hypertonicity. Proc. Natl. Acad. Sci. U. S. A. 96: 2538-2542. http://dx.doi.org/10.1073/pnas.96.5.2538.
104. López-Rodríguez C, Aramburu J, Jin L, Rakeman AS, Michino M, Rao A. 2001. Bridging the NFAT and NF-kappaB families: NFAT5 dimerization regulates cytokine gene transcription in response to osmotic stress. Immunity 15: 47-58. http://dx.doi.org/10.1016/S1074-7613(01)00165-0.
105. Graef IA, Chen F, Chen L, Kuo A, Crabtree GR. 2001. Signals transduced by Ca(2+)/calcineurin and NFATc3/c4 pattern the developing vasculature. Cell 105: 863-875. http://dx.doi.org/10.1016/S0092-8674(01)00396-8.
106. Graef IA, Wang F, Charron F, Chen L, Neilson J, Tessier-Lavigne M, Crabtree GR. 2003. Neurotrophins and netrins require calcineurin/ NFAT signaling to stimulate outgrowth of embryonic axons. Cell 113: 657-670. http://dx.doi.org/10.1016/S0092-8674(03)00390-8.
107. Nguyen T, Lindner R, Tedeschi A, Forsberg K, Green A, Wuttke A, Gaub P, Di Giovanni S. 2009. NFAT-3 is a transcriptional repressor of the growth-associated protein 43 during neuronal maturation. J. Biol. Chem. 284: 18816-18823. http://dx.doi.org/10.1074/jbc.M109.015719.
108. Korshunova I, Mosevitsky M. 2010. Role of the growth-associated protein GAP-43 in NCAM-mediated neurite outgrowth. Adv. Exp. Med. Biol. 663: 169-182. http://dx.doi.org/10.1007/978-1-4419-1170-4_11.
109. Spires-Jones TL, Kay K, Matsouka R, Rozkalne A, Betensky RA, Hyman BT. 2011. Calcineurin inhibition with systemic FK506 treatment increases dendritic branching and dendritic spine density in healthy adult mouse brain. Neurosci. Lett. 487: 260-263. http://dx.doi.org/10.1016/j.neulet.2010.10.033.
110. Wu HY, Hudry E, Hashimoto T, Kuchibhotla K, Rozkalne A, Fan Z, Spires-Jones T, Xie H, Arbel-Ornath M, Grosskreutz CL, Bacskai BJ, Hyman BT. 2010. Amyloid beta induces the morphological neurodegenerative triad of spine loss, dendritic simplification, and neuritic dystrophies through calcineurin activation. J. Neurosci. 30: 2636-2649. http://dx.doi.org/10.1523/JNEUROSCI.4456-09.2010.
111. Huang C, Mattjus P, Ma WY, Rincon M, Chen NY, Brown RE, Dong Z. 2000. Involvement of nuclear factor of activated T cells activation in UV response. Evidence from cell culture and transgenic mice. J. Biol. Chem. 275: 9143-9149. http://dx.doi.org/10.1074/jbc.275.13.9143.
112. Fürstenau U, Schwaninger M, Blume R, Jendrusch EM, Knepel W. 1999. Characterization of a novel calcium response element in the glucagon gene. J. Biol. Chem. 274: 5851-5860. http://dx.doi.org/10.1074/jbc.274.9.5851.
113. Lawrence MC, Bhatt HS, Easom RA. 2002. NFAT regulates insulin gene promoter activity in response to synergistic pathways induced by glucose and glucagon-like peptide-1. Diabetes 51: 691-698. http://dx.doi.org/10.2337/diabetes.51.3.691.
114. Lawrence MC, Bhatt HS, Watterson JM, Easom RA. 2001. Regulation of insulin gene transcription by a Ca(2+)-responsive pathway involving calcineurin and nuclear factor of activated T cells. Mol. Endocrinol. 15: 1758-1767.
115. Heit JJ. 2007. Calcineurin/NFAT signaling in the beta-cell: From diabetes to new therapeutics. Bioessays 29: 1011-1021. http://dx.doi.org/10.1002/bies.20644.
116. Bousette N, Chugh S, Fong V, Isserlin R, Kim KH, Volchuk A, Backx PH, Liu P, Kislinger T, MacLennan DH, Emili A, Gramolini AO. 2010. Constitutively active calcineurin induces cardiac endoplasmic reticulum stress and protects against apoptosis that is mediated by alphacrystallin-B. Proc. Natl. Acad. Sci. U. S. A. 107: 18481-18486. http://dx.doi.org/10.1073/pnas.1013555107.
117. Edgar RC. 2004. MUSCLE: a multiple sequence alignment method with reduced time and space complexity. BMC Bioinformatics 5: 113. http://dx.doi.org/10.1186/1471-2105-5-113.
118. Edgar RC. 2004. MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res. 32: 1792-1797. http://dx.doi.org/10.1093/nar/gkh340.
119. Castresana J. 2000. Selection of conserved blocks from multiple alignments for their use in phylogenetic analysis. Mol. Biol. Evol. 17: 540-552. http://dx.doi.org/10.1093/oxfordjournals.molbev.a026334.
120. Milne I, Lindner D, Bayer M, Husmeier D, McGuire G, Marshall DF, Wright F. 2009. TOPALi v2: a rich graphical interface for evolutionary analyses of multiple alignments on HPC clusters and multi-core desktops. Bioinformatics 25: 126-127. http://dx.doi.org/10.1093/bioinformatics/btn575.