CBC轉錄因子在不同環境刺激下調控白色念珠菌致病因子之探討

簡易檢索 / 詳目顯示

回結果列表

研究生：	許博琛 Hsu, Po-Chen
論文名稱：	CBC轉錄因子在不同環境刺激下調控白色念珠菌致病因子之探討 Contributions of CCAAT-binding Complex to Regulation of Candida albicans Virulence Traits in Response to Environmental Perturbations
指導教授：	藍忠昱 Lan, Chung-Yu
口試委員:	王雯靜楊昀良楊程堯張壯榮
學位類別：	博士 Doctor
系所名稱：	生命科學暨醫學院 - 分子與細胞生物研究所 Institute of Molecular and Cellular Biology
論文出版年：	2013
畢業學年度：	101
語文別：	英文
論文頁數：	142
中文關鍵詞：	白色念珠菌、CCAAT序列結合蛋白、致病因子、鐵平衡調控、菌絲生成、Rapamycin標靶蛋白訊息傳遞鏈
外文關鍵詞：	Candida albicans, CCAAT-binding complex, Virulence factor, Iron homeostasis, Filamentation, TOR signaling
相關次數：	點閱：1 下載：0
分享至:	分享至facebook 分享至twitter

查詢本校圖書館目錄查詢臺灣博碩士論文知識加值系統勘誤回報

CCAAT為普遍存在於真核生物基因體之中的DNA序列。生物體中負責辨識並結合在CCAAT序列上的蛋白複合體被命名為「CCAAT-binding complex」，簡稱為CBC。CBC的胺基酸序列在演化上高度保存於真菌、植物及哺乳類動物之中。CBC可自行調節基因轉錄，亦可藉由與其它轉錄因子共同合作來進行轉錄調控。Hap43蛋白是在白色念珠菌的研究中第一個被鑑定為可跟CBC結合並共同作用的轉錄因子。本研究中先進行Hap43的功能分析。結果初步確認Hap43是一個在缺鐵環境中會被活化的抑制型轉錄因子，專門負責在鐵離子不足的情況下壓制「需鐵類型蛋白」之基因的轉錄。另外，缺鐵環境可促使Hap43聚集在細胞核內，同時Hap43調控基因表達的功能需仰賴CBC的存在。然而，迄今在白色念珠菌的研究中，CBC是否具有不需與Hap43協同作用的功能仍不清楚。因此本研究的第二部份著重於CBC總體的功能分析，發現了CBC負責調控許多白色念珠菌的致病因子。另外，藉由比較正常菌株及CBC剃除菌株的全基因體轉錄變化情形，推測CBC亦負責「核醣體生合成」和「轉譯作用」的負向調控，以及「缺氮反應」的正向調控。同時CBC還負責調控數種重要的表現型，包括「低氮環境激發的菌絲生成」、「使用蛋白質分解後獲得之氮源的能力」，及「抑制酵母菌細胞凝集作用」。有趣的是，上位基因效應分析的結果推測出CBC隸屬於Rhb1-TOR訊息傳遞鏈，同時CBC可利用Mep2-Ras1-PKA/MAPK的訊息傳遞途徑來控制「低氮環境激發的菌絲生成」。最後，本研究將HAP43及CBC基因突變後，發現會降低白色念珠菌的致病力。總結來說，本研究發掘CBC蛋白複合體在接受環境變化刺激後調控白色念珠菌致病因子之重要角色。這些發現不僅有助於了解白色念珠菌，同時還可能被借鏡到其它人類致病真菌的病理研究。

The CCAAT-motif is ubiquitous in promoters of eukaryotic genomes. The CCAAT-binding complex (CBC), which is conserved from fungi to plants, to mammals, specifically recognizes the CCAAT-motif and modulates transcription directly or in cooperation with other transcription factors. In Candida albicans, Hap43 was identified to interact with CBC. In this study, the function of Hap43 was first characterized. The results demonstrated that Hap43 is a low iron–induced transcription factor and is responsible for repression of genes encoding iron-dependent proteins in response to iron deprivation. Iron deprived conditions can induce the nuclear localization of Hap43. Moreover, Hap43-mediated regulation was shown to depend on the presence of CBC. However, it is unclear whether CBC can function independently of Hap43. The Hap43-independent role of CBC in C. albicans was further explored and the results showed that CBC acts as a novel regulator of virulence traits. Genome-wide transcriptional profiling suggested that CBC contributes to negative regulation of ribosome biogenesis and translation and positive regulation of nitrogen starvation-mediated responses. CBC was also required for low nitrogen–induced filamentation, utilization of nitrogen sources from proteins, and repression of flocculation phenotype. Interestingly, epistasis analyses suggested that CBC is an important downstream effector of Rhb1-TOR signaling and controls low nitrogen–induced filamentation via the Mep2-Ras1-PKA/MAPK pathway. Finally, deletion of HAP43 and CBC genes attenuated C. albicans virulence. This study therefore highlights the crucial role of C. albicans CBC in regulating multiple virulence traits in response to environmental perturbations. These findings not only provide basic information for C. albicans per se but also may increase our understanding of the pathogenesis of other human fungal pathogens.

Abstract    I
摘要    II
誌謝辭    III
Table of Contents    IV
List of publications    IX
Abbreviations    X
Chapter 1. Introduction    1
1.1 Candida albicans and candidiasis    2
1.2 Important virulence traits of C. albicans    3
1.3 Adaptation of C. albicans to environments    4
1.4 The CCAAT-binding complex    6
1.4.1 Mammalian CBC, NF-Y, and fungal CBC    6
1.4.2 Fungal CBC and Hap4/HapX/Hap43    7
1.4.3 Potential functions of CBC    7
1.4.4 C. albicans CBC    8
1.5 Specific aims    8
Chapter 2. Materials and Methods    11
2.1 Growth media    12
2.1.1 Media for strain constructions    12
2.1.2 Media for iron-dependent assays    12
2.1.3 Media for nitrogen-related assays    13
2.1.4 Rapamycin-containing media    13
2.2 Strain constructions    13
2.2.1 C. albicans competent cell preparation and transformation    14
2.2.2 HAP43 and SFU1 deletions    14
2.2.3 HAP5, HAP32, HAP31, and HAP2 gene deletions    16
2.2.4 Construction of Hap43 one-hybrid strains    16
2.2.5 GFP-Hap43 expressing strains    17
2.2.6 Strains for promoter analysis    18
2.2.7 MEP2C440 and RAS1G13V-expressing strains    18
2.2.8 RHB1 deletion    18
2.2.9 Construction of promoter swapping strains    18
2.2.10 Construction of ADH1p-driven overexpression strains    19
2.2.11 Southern blotting    19
2.3 DNA microarray analysis    20
2.3.1 Sample preparations    20
2.3.2 DNA microarray design    21
2.3.3 Microarray data analysis    21
2.4 Gene expression quantitation    21
2.4.1 RNA extraction    21
2.4.2 Reverse transcription    22
2.4.3 Real-time quantitative PCR    22
2.5 One-hybrid analysis    23
2.6 Promoter analysis    24
2.7 Filamentation assay and growth-dependent spot assay    24
2.8 Flocculation assay    25
2.9 Virulence assay    25
2.9.1 Murine infection model    25
2.9.2 Zebrafish infection model    26
2.9.3 Statistic analysis    26
2.10 Fluorescence microscopy    27
2.11 Protein extraction and western blotting    27
2.12 Flaving secretion assay    28
Chapter 3. Results    29
3.1 Identification of Hap43 as an essential regulator for iron homeostasis in C. albicans    30
3.1.1 C. albicans Hap43 contains a region that is highly conserved to the N-terminus of fungal HapX/Php4.    30
3.1-2 Hap43 is essential for cell growth in low-iron conditions.    31
3.1.3 Hap43 is responsible for repressing iron-utilization genes in low-iron conditions.    32
3.2 Iron-responsive activity of Hap43    35
3.2.1 Environmental iron affects the transcriptional activity of Hap43.    35
3.2.2 Hap43 becomes a transcriptional repressor in the low-iron conditions.    37
3.2.3 Iron limitation induces the nuclear accumulation of Hap43.    37
3.3 Contribution of Hap43 to C. albicans virulence    39
3.4 CBC potentially co-operates with Hap43 to regulate low iron–induced responses    40
3.4.1 Hap43 and Tup1 are required for low iron–induced flavinogenesis.    40
3.4.2 CBC mutants phenocopy the hap43 null mutant in flavinogenesis.    41
3.5 Regulatory roles of CBC in different environmental conditions    41
3.5.1 CBC is essential for cell growth in low-iron conditions.    41
3.5.2 CBC and CCAAT-motif are required for low iron−induced gene repression.    41
3.5.3 Responses to TOR inhibition by rapamycin revealed that CBC plays potential roles in low-nitrogen conditions.    42
3.6 Differential expression of the two Hap3 paralogs, Hap31 and Hap32    43
3.6.1 HAP32 and HAP31 are differentially expressed in response to different environmental conditions.    44
3.6.2 Expression of HAP32 controlled by HAP31 promoter is unable to complement the defect resulted from loss of HAP31.    44
3.7 Role of CBC in rapamycin-responsive gene regulation    45
3.8 Regulation of low nitrogen–induced filamentation by CBC    47
3.9 Negative regulation by CBC in flocculation in unfavorable conditions    48
3.9.1 Deletions of CBC cause extensive cellular flocculation.    48
3.9.2 Flocculation of CBC mutant cells may result from elevated level of cell surface adhesins.    50
3.10 CBC plays a positive role in nitrogen utilization    50
3.11 Contribution of CBC to C. albicans virulence    51
Chapter 4. Discussion    52
4.1 Hap43 and its homologs.    53
4.2 Hap43 and C. albicans virulence    53
4.3 Regulatory role of Hap43 in iron-responsive gene expression    55
4.4 Iron-responsive translocalization of Hap43    56
4.5 Hap43 and co-repressor Tup1    57
4.6 Hap43-mediated transcriptional repression relies on CBC.    57
4.7 CBC is a downstream effector of TOR signaling in iron-independent conditions.    58
4.8 CBC regulates different virulence traits during C. albicans infection    60
4.9 CBC may act as a global complex for multiple transcription factors    62
4.10 CBC-mediated transcription is simultaneously affected by multiple environmental stimuli    63
Chapter 5. Concluding remarks    67
5.1 A working model for Hap43 functions    68
5.2 CBC functions in C. albicans    68
5.3 Perspectives    69
References    70
Figures    83
Figure 1. Construction of hap43 null mutant.    83
Figure 2. Deletion of C. albicans HAP43 causes growth defects in low-iron conditions.    85
Figure 3. Hap43 represses the transcription of genes encoding iron-dependent proteins in low-iron conditions.    86
Figure 4. One-hybrid analysis demonstrated that Hap43 is an activator under iron-rich conditions and a repressor under iron-deficient conditions.    88
Figure 5. Iron deficiency induces nuclear accumulation of Hap43.    90
Figure 6. Deletion of HAP43 attenuates C. albicans virulence.    92
Figure 7. Hap43 and CBC are essential for the flavinogenesis induced by iron starvation.    94
Figure 8. Deletion of CBC abolishes low iron–mediated cell responses.    95
Figure 9. CBC mutants are insensitive to rapamycin inhibition of Tor1.    97
Figure 10. Excess Hap32 or low levels of Hap31 can complement the rapamycin resistance of the hap31 mutant.    99
Figure 11. Comparisons between the hap5 null mutant and the wild type in their responses regarding rapamycin-mediated gene expression.    100
Figure 12. CBC is required for low nitrogen–induced filamentation mediated by Mep2 and functions downstream of Rhb1-TOR.    102
Figure 13. CBC negatively regulates cellular aggregation by repressing expression of adhesin genes in the unfavorable condition.    104
Figure 14. CBC is required for digestion and utilization of proteins.    106
Figure 15. CBC is important for C. albicans virulence in a zebrafish model of peritoneal infection.    107
Figure 16. Model for CBC-mediated transcriptional regulation in C. albicans.    108
Figure 17. Simple model for Hap43-mediated iron metabolism.    109
Tables    110
Table 1. Strains used in phenotypic assays and gene expression assays.    110
Table 2. Strains used in one-hybrid assays.    114
Table 3. Strains used in confocal microscopy and western blotting.    116
Table 4. Plasmids used in this study.    117
Table 5. Primers and oligonucleotides used in strain constructions.    120
Table 6. Primers used in quantitative real-time PCR.    130
Table 7. Genes that are down-regulated and involved in nitrogen utilization in the hap5 null mutant.    132
Supplementary information    134
Figure S1. Site-directed mutagenesis of the CCAAT-motif in the MEP2 promoter reduces low nitrogen–induced gene expression.    134
Figure S2. HAP31 and HAP32 are differentially expressed in response to the availability of iron, ammonium, BSA, and rapamycin.    135
Figure S3. Amino acid sequence alignment of Hap32 and Hap31.    136
Figure S4. CBC is required for repression of adhesin genes in stationary-phase cells in the unfavorable condition.    137
Figure S5. Rapamycin induces the expression of adhesin genes in CBC mutants.    138
Figure S6. CBC is required for C. albicans virulence in a murine model of systemic infection.    139
Figure S7. Epistasis analysis suggests that Npr1 acts downstream of Rhb1/TOR and is independent of CBC.    140
Figure S8. Expression of HAP32, but not HAP31, is regulated by CBC when BSA is the sole nitrogen source.    141
Table S1. Differentially expressed genes in the hap5 null mutant compared with wild type.    142

                                

1. Barnett JA. 2008. A history of research on yeasts 12: medical yeasts part 1, Candida albicans. Yeast 25:385-417.
2. Calderone RA, Clancy CJ. 2012. Candida and candidiasis, 2nd ed. ASM Press, Washington, DC.
3. Fitzpatrick DA, Logue ME, Stajich JE, Butler G. 2006. A fungal phylogeny based on 42 complete genomes derived from supertree and combined gene analysis. BMC evolutionary biology 6:99.
4. Sobel JD. 2007. Vulvovaginal candidosis. Lancet 369:1961-1971.
5. Sobel JD. 1998. Vulvovaginitis due to Candida glabrata. An emerging problem. Mycoses 41 Suppl 2:18-22.
6. Coleman DC, Bennett DE, Sullivan DJ, Gallagher PJ, Henman MC, Shanley DB, Russell RJ. 1993. Oral Candida in HIV infection and AIDS: new perspectives/new approaches. Critical reviews in microbiology 19:61-82.
7. Vargas KG, Joly S. 2002. Carriage frequency, intensity of carriage, and strains of oral yeast species vary in the progression to oral candidiasis in human immunodeficiency virus-positive individuals. Journal of clinical microbiology 40:341-350.
8. Warnock DW. 2007. Trends in the epidemiology of invasive fungal infections. Nihon Ishinkin Gakkai zasshi = Japanese journal of medical mycology 48:1-12.
9. Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB. 2004. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 39:309-317.
10. Perlroth J, Choi B, Spellberg B. 2007. Nosocomial fungal infections: epidemiology, diagnosis, and treatment. Medical mycology : official publication of the International Society for Human and Animal Mycology 45:321-346.
11. Pfaller MA, Diekema DJ. 2007. Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev 20:133-163.
12. Calderone RA, Fonzi WA. 2001. Virulence factors of Candida albicans. Trends Microbiol 9:327-335.
13. Yang YL. 2003. Virulence factors of Candida species. Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi 36:223-228.
14. Biswas S, Van Dijck P, Datta A. 2007. Environmental sensing and signal transduction pathways regulating morphopathogenic determinants of Candida albicans. Microbiology and molecular biology reviews : MMBR 71:348-376.
15. Sudbery PE. 2011. Growth of Candida albicans hyphae. Nat Rev Microbiol 9:737-748.
16. Whiteway M, Bachewich C. 2007. Morphogenesis in Candida albicans. Annu Rev Microbiol 61:529-553.
17. Lo HJ, Kohler JR, DiDomenico B, Loebenberg D, Cacciapuoti A, Fink GR. 1997. Nonfilamentous C. albicans mutants are avirulent. Cell 90:939-949.
18. Saville SP, Lazzell AL, Monteagudo C, Lopez-Ribot JL. 2003. Engineered control of cell morphology in vivo reveals distinct roles for yeast and filamentous forms of Candida albicans during infection. Eukaryot Cell 2:1053-1060.
19. Sundstrom P. 2002. Adhesion in Candida spp. Cellular microbiology 4:461-469.
20. Hoyer LL, Green CB, Oh SH, Zhao X. 2008. Discovering the secrets of the Candida albicans agglutinin-like sequence (ALS) gene family--a sticky pursuit. Medical mycology : official publication of the International Society for Human and Animal Mycology 46:1-15.
21. Staab JF, Ferrer CA, Sundstrom P. 1996. Developmental expression of a tandemly repeated, proline-and glutamine-rich amino acid motif on hyphal surfaces on Candida albicans. J Biol Chem 271:6298-6305.
22. Staab JF, Sundstrom P. 1998. Genetic organization and sequence analysis of the hypha-specific cell wall protein gene HWP1 of Candida albicans. Yeast 14:681-686.
23. Li F, Palecek SP. 2003. EAP1, a Candida albicans gene involved in binding human epithelial cells. Eukaryot Cell 2:1266-1273.
24. de Repentigny L, Aumont F, Bernard K, Belhumeur P. 2000. Characterization of binding of Candida albicans to small intestinal mucin and its role in adherence to mucosal epithelial cells. Infect Immun 68:3172-3179.
25. King RD, Lee JC, Morris AL. 1980. Adherence of Candida albicans and other Candida species to mucosal epithelial cells. Infect Immun 27:667-674.
26. Martin R, Wachtler B, Schaller M, Wilson D, Hube B. 2011. Host-pathogen interactions and virulence-associated genes during Candida albicans oral infections. International journal of medical microbiology : IJMM 301:417-422.
27. Schaller M, Borelli C, Korting HC, Hube B. 2005. Hydrolytic enzymes as virulence factors of Candida albicans. Mycoses 48:365-377.
28. Hube B, Sanglard D, Odds FC, Hess D, Monod M, Schafer W, Brown AJ, Gow NA. 1997. Disruption of each of the secreted aspartyl proteinase genes SAP1, SAP2, and SAP3 of Candida albicans attenuates virulence. Infect Immun 65:3529-3538.
29. Sanglard D, Hube B, Monod M, Odds FC, Gow NA. 1997. A triple deletion of the secreted aspartyl proteinase genes SAP4, SAP5, and SAP6 of Candida albicans causes attenuated virulence. Infect Immun 65:3539-3546.
30. Dalle F, Wachtler B, L'Ollivier C, Holland G, Bannert N, Wilson D, Labruere C, Bonnin A, Hube B. 2010. Cellular interactions of Candida albicans with human oral epithelial cells and enterocytes. Cellular microbiology 12:248-271.
31. Leidich SD, Ibrahim AS, Fu Y, Koul A, Jessup C, Vitullo J, Fonzi W, Mirbod F, Nakashima S, Nozawa Y, Ghannoum MA. 1998. Cloning and disruption of caPLB1, a phospholipase B gene involved in the pathogenicity of Candida albicans. J Biol Chem 273:26078-26086.
32. Theiss S, Ishdorj G, Brenot A, Kretschmar M, Lan CY, Nichterlein T, Hacker J, Nigam S, Agabian N, Kohler GA. 2006. Inactivation of the phospholipase B gene PLB5 in wild-type Candida albicans reduces cell-associated phospholipase A2 activity and attenuates virulence. International journal of medical microbiology : IJMM 296:405-420.
33. Calderone RA. 2002. Candida and candidiasis. ASM Press, Washington, D.C.
34. Brock M. 2009. Fungal metabolism in host niches. Curr Opin Microbiol 12:371-376.
35. Fleck CB, Schobel F, Brock M. 2011. Nutrient acquisition by pathogenic fungi: nutrient availability, pathway regulation, and differences in substrate utilization. International journal of medical microbiology : IJMM 301:400-407.
36. Cottier F, Muhlschlegel FA. 2009. Sensing the environment: response of Candida albicans to the X factor. FEMS Microbiol Lett 295:1-9.
37. Shapiro RS, Cowen LE. 2012. Uncovering cellular circuitry controlling temperature-dependent fungal morphogenesis. Virulence 3.
38. Shapiro RS, Cowen LE. 2012. Uncovering cellular circuitry controlling temperature-dependent fungal morphogenesis. Virulence 3:400-404.
39. Slutsky B, Buffo J, Soll DR. 1985. High-frequency switching of colony morphology in Candida albicans. Science 230:666-669.
40. Huang G. 2012. Regulation of phenotypic transitions in the fungal pathogen Candida albicans. Virulence 3:251-261.
41. Soll DR. 2002. Candida commensalism and virulence: the evolution of phenotypic plasticity. Acta tropica 81:101-110.
42. Lan CY, Rodarte G, Murillo LA, Jones T, Davis RW, Dungan J, Newport G, Agabian N. 2004. Regulatory networks affected by iron availability in Candida albicans. Mol Microbiol 53:1451-1469.
43. Woodacre A, Mason RP, Jeeves RE, Cashmore AM. 2008. Copper-dependent transcriptional regulation by Candida albicans Mac1p. Microbiology 154:1502-1512.
44. Kim MJ, Kil M, Jung JH, Kim J. 2008. Roles of Zinc-responsive transcription factor Csr1 in filamentous growth of the pathogenic Yeast Candida albicans. Journal of microbiology and biotechnology 18:242-247.
45. Philpott CC, Leidgens S, Frey AG. 2012. Metabolic remodeling in iron-deficient fungi. Biochim Biophys Acta 1823:1509-1520.
46. Chen C, Pande K, French SD, Tuch BB, Noble SM. 2011. An iron homeostasis regulatory circuit with reciprocal roles in Candida albicans commensalism and pathogenesis. Cell host & microbe 10:118-135.
47. Hsu PC, Yang CY, Lan CY. 2011. Candida albicans Hap43 is a repressor induced under low-iron conditions and is essential for iron-responsive transcriptional regulation and virulence. Eukaryot Cell 10:207-225.
48. Singh RP, Prasad HK, Sinha I, Agarwal N, Natarajan K. 2011. Cap2-HAP complex is a critical transcriptional regulator that has dual but contrasting roles in regulation of iron homeostasis in Candida albicans. J Biol Chem 286:25154-25170.
49. Mantovani R. 1999. The molecular biology of the CCAAT-binding factor NF-Y. Gene 239:15-27.
50. Mantovani R. 1998. A survey of 178 NF-Y binding CCAAT boxes. Nucleic Acids Res 26:1135-1143.
51. Maity SN, de Crombrugghe B. 1998. Role of the CCAAT-binding protein CBF/NF-Y in transcription. Trends Biochem Sci 23:174-178.
52. Bucher P. 1990. Weight matrix descriptions of four eukaryotic RNA polymerase II promoter elements derived from 502 unrelated promoter sequences. J Mol Biol 212:563-578.
53. Pinkham JL, Guarente L. 1985. Cloning and molecular analysis of the HAP2 locus: a global regulator of respiratory genes in Saccharomyces cerevisiae. Mol Cell Biol 5:3410-3416.
54. McNabb DS, Xing Y, Guarente L. 1995. Cloning of yeast HAP5: a novel subunit of a heterotrimeric complex required for CCAAT binding. Genes Dev 9:47-58.
55. Hahn S, Guarente L. 1988. Yeast HAP2 and HAP3: transcriptional activators in a heteromeric complex. Science 240:317-321.
56. Olesen J, Hahn S, Guarente L. 1987. Yeast HAP2 and HAP3 activators both bind to the CYC1 upstream activation site, UAS2, in an interdependent manner. Cell 51:953-961.
57. Mulder W, Scholten IH, de Boer RW, Grivell LA. 1994. Sequence of the HAP3 transcription factor of Kluyveromyces lactis predicts the presence of a novel 4-cysteine zinc-finger motif. Mol Gen Genet 245:96-106.
58. Nguyen C, Bolotin-Fukuhara M, Wesolowski-Louvel M, Fukuhara H. 1995. The respiratory system of Kluyveromyces lactis escapes from HAP2 control. Gene 152:113-115.
59. McNabb D, Tseng K, Guarente L. 1997. The Saccharomyces cerevisiae Hap5p homolog from fission yeast reveals two conserved domains that are essential for assembly of heterotetrameric CCAAT-binding factor. Mol. Cell. Biol. 17:7008-7018.
60. Olesen JT, Fikes JD, Guarente L. 1991. The Schizosaccharomyces pombe homolog of Saccharomyces cerevisiae HAP2 reveals selective and stringent conservation of the small essential core protein domain. Mol Cell Biol 11:611-619.
61. Brakhage AA, Andrianopoulos A, Kato M, Steidl S, Davis MA, Tsukagoshi N, Hynes MJ. 1999. HAP-Like CCAAT-binding complexes in filamentous fungi: implications for biotechnology. Fungal genetics and biology : FG & B 27:243-252.
62. Jung WH, Saikia S, Hu G, Wang J, Fung CK, D'Souza C, White R, Kronstad JW. 2010. HapX positively and negatively regulates the transcriptional response to iron deprivation in Cryptococcus neoformans. PLoS Pathog 6:e1001209.
63. Johnson DC, Cano KE, Kroger EC, McNabb DS. 2005. Novel Regulatory Function for the CCAAT-Binding Factor in Candida albicans. Eukaryotic Cell 4:1662-1676.
64. Baek Y-U, Li M, Davis DA. 2008. Candida albicans Ferric Reductases Are Differentially Regulated in Response to Distinct Forms of Iron Limitation by the Rim101 and CBF Transcription Factors. Eukaryotic Cell 7:1168-1179.
65. Xing Y, Fikes JD, Guarente L. 1993. Mutations in yeast HAP2/HAP3 define a hybrid CCAAT box binding domain. EMBO J 12:4647-4655.
66. Steidl S, Tuncher A, Goda H, Guder C, Papadopoulou N, Kobayashi T, Tsukagoshi N, Kato M, Brakhage AA. 2004. A single subunit of a heterotrimeric CCAAT-binding complex carries a nuclear localization signal: piggy back transport of the pre-assembled complex to the nucleus. J Mol Biol 342:515-524.
67. Goda H, Nagase T, Tanoue S, Sugiyama J, Steidl S, Tuncher A, Kobayashi T, Tsukagoshi N, Brakhage AA, Kato M. 2005. Nuclear translocation of the heterotrimeric CCAAT binding factor of Aspergillus oryzae is dependent on two redundant localising signals in a single subunit. Archives of microbiology 184:93-100.
68. Forsburg SL, Guarente L. 1989. Identification and characterization of HAP4: a third component of the CCAAT-bound HAP2/HAP3 heteromer. Genes Dev 3:1166-1178.
69. Zitomer RS, Lowry CV. 1992. Regulation of gene expression by oxygen in Saccharomyces cerevisiae. Microbiological reviews 56:1-11.
70. Mercier A, Watt S, Bahler J, Labbe S. 2008. Key Function for the CCAAT-Binding Factor Php4 To Regulate Gene Expression in Response to Iron Deficiency in Fission Yeast. Eukaryotic Cell 7:493-508.
71. Bourgarel D, Nguyen CC, Bolotin-Fukuhara M. 1999. HAP4, the glucose-repressed regulated subunit of the HAP transcriptional complex involved in the fermentation-respiration shift, has a functional homologue in the respiratory yeast Kluyveromyces lactis. Mol Microbiol 31:1205-1215.
72. Hortschansky P, Eisendle M, Al-Abdallah Q, Schmidt AD, Bergmann S, Thon M, Kniemeyer O, Abt B, Seeber B, Werner ER, Kato M, Brakhage AA, Haas H. 2007. Interaction of HapX with the CCAAT-binding complex--a novel mechanism of gene regulation by iron. EMBO J 26:3157-3168.
73. Schrettl M, Beckmann N, Varga J, Heinekamp T, Jacobsen ID, Jochl C, Moussa TA, Wang S, Gsaller F, Blatzer M, Werner ER, Niermann WC, Brakhage AA, Haas H. 2010. HapX-mediated adaption to iron starvation is crucial for virulence of Aspergillus fumigatus. PLoS Pathog 6:e1001124.
74. Bungartz G, Land H, Scadden DT, Emerson SG. 2012. NF-Y is necessary for hematopoietic stem cell proliferation and survival. Blood 119:1380-1389.
75. Luo R, Klumpp SA, Finegold MJ, Maity SN. 2011. Inactivation of CBF/NF-Y in postnatal liver causes hepatocellular degeneration, lipid deposition, and endoplasmic reticulum stress. Scientific reports 1:136.
76. Imbriano C, Gnesutta N, Mantovani R. 2012. The NF-Y/p53 liaison: Well beyond repression. Biochim Biophys Acta 1825:131-139.
77. Bannwarth S, Laine S, Daher A, Grandvaux N, Clerzius G, Leblanc AC, Hiscott J, Gatignol A. 2006. Cell-specific regulation of TRBP1 promoter by NF-Y transcription factor in lymphocytes and astrocytes. J Mol Biol 355:898-910.
78. Laloum T, De Mita S, Gamas P, Baudin M, Niebel A. 2013. CCAAT-box binding transcription factors in plants: Y so many? Trends in plant science 18:157-166.
79. Thon M, Al Abdallah Q, Hortschansky P, Scharf DH, Eisendle M, Haas H, Brakhage AA. 2010. The CCAAT-binding complex coordinates the oxidative stress response in eukaryotes. Nucleic Acids Res 38:1098-1113.
80. Homann OR, Dea J, Noble SM, Johnson AD. 2009. A phenotypic profile of the Candida albicans regulatory network. PLoS Genet 5:e1000783.
81. Linde J, Wilson D, Hube B, Guthke R. 2010. Regulatory network modelling of iron acquisition by a fungal pathogen in contact with epithelial cells. BMC systems biology 4:148.
82. Tierney L, Linde J, Muller S, Brunke S, Molina JC, Hube B, Schock U, Guthke R, Kuchler K. 2012. An Interspecies Regulatory Network Inferred from Simultaneous RNA-seq of Candida albicans Invading Innate Immune Cells. Frontiers in microbiology 3:85.
83. Crandall M, Edwards JE, Jr. 1987. Segregation of proteinase-negative mutants from heterozygous Candida albicans. Journal of general microbiology 133:2817-2824.
84. Chen YT, Lin CY, Tsai PW, Yang CY, Hsieh WP, Lan CY. 2012. Rhb1 regulates the expression of secreted aspartic protease 2 through the TOR signaling pathway in Candida albicans. Eukaryot Cell 11:168-182.
85. Reuß O, Vik Å, Kolter R, Morschhäuser J. 2004. The SAT1 flipper, an optimized tool for gene disruption in Candida albicans. Gene 341:119-127.
86. Reuss O, Morschhauser J. 2006. A family of oligopeptide transporters is required for growth of Candida albicans on proteins. Mol Microbiol 60:795-812.
87. Geber A, Williamson PR, Rex JH, Sweeney EC, Bennett JE. 1992. Cloning and characterization of a Candida albicans maltase gene involved in sucrose utilization. J Bacteriol 174:6992-6996.
88. Hube B, Monod M, Schofield DA, Brown AJP, Gow NAR. 1994. Expression of seven members of the gene family encoding secretory aspartyl proteinases in <i>Candida albicans</i>. Molecular Microbiology 14:87-99.
89. Russell CL, Brown AJP. 2005. Expression of one-hybrid fusions with Staphylococcus aureus lexA in Candida albicans confirms that Nrg1 is a transcriptional repressor and that Gcn4 is a transcriptional activator. Fungal Genetics and Biology 42:676-683.
90. Park Y-N, Morschhauser J. 2005. Tetracycline-Inducible Gene Expression and Gene Deletion in Candida albicans. Eukaryotic Cell 4:1328-1342.
91. Ramanan N, Wang Y. 2000. A high-affinity iron permease essential for Candida albicans virulence. Science 288:1062-1064.
92. Gaur NA, Manoharlal R, Saini P, Prasad T, Mukhopadhyay G, Hoefer M, Morschhauser J, Prasad R. 2005. Expression of the CDR1 efflux pump in clinical Candida albicans isolates is controlled by a negative regulatory element. Biochemical and biophysical research communications 332:206-214.
93. Tsao CC, Chen YT, Lan CY. 2009. A small G protein Rhb1 and a GTPase-activating protein Tsc2 involved in nitrogen starvation-induced morphogenesis and cell wall integrity of Candida albicans. Fungal genetics and biology : FG & B 46:126-136.
94. Sambrook J, Russell DW. 2001. Molecular cloning : a laboratory manual, 3rd ed. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.
95. Schaller M, Schafer W, Korting HC, Hube B. 1998. Differential expression of secreted aspartyl proteinases in a model of human oral candidosis and in patient samples from the oral cavity. Mol Microbiol 29:605-615.
96. Rupp S. 2002. LacZ assays in yeast, p. 112-131. In Christine G, Gerald RF (ed.), Methods in Enzymology, vol. Volume 350. Academic Press.
97. Chao CC, Hsu PC, Jen CF, Chen IH, Wang CH, Chan HC, Tsai PW, Tung KC, Lan CY, Chuang YJ. 2010. Zebrafish as a model host for Candida albicans infection. Infect Immun 78:2512-2521.
98. Macheroux P. 1999. UV-Visible Spectroscopy as a Tool to Study Flavoproteins, p. 1-7.
99. Knight SAB, Lesuisse E, Stearman R, Klausner RD, Dancis A. 2002. Reductive iron uptake by Candida albicans: role of copper, iron and the TUP1 regulator. Microbiology 148:29-40.
100. Campanella JJ, Bitincka L, Smalley J. 2003. MatGAT: an application that generates similarity/identity matrices using protein or DNA sequences. BMC Bioinformatics 4:29.
101. Kaplan J, McVey Ward D, Crisp RJ, Philpott CC. 2006. Iron-dependent metabolic remodeling in S. cerevisiae. Biochim Biophys Acta 1763:646-651.
102. Lill R, Muhlenhoff U. 2006. Iron-sulfur protein biogenesis in eukaryotes: Components and mechanisms. Annu. Rev. Cell Dev. Biol. 22:457-486.
103. Craig EA, Marszalek J. 2002. A specialized mitochondrial molecular chaperone system: A role in formation of Fe/S centers. Cell. Mol. Life Sci. 59:1658-1665.
104. Lill R, Muhlenhoff U. 2005. Iron-sulfur-protein biogenesis in eukaryotes. Trends Biochem.Sci. 30:133-141.
105. Rouault TA, Tong WH. 2005. Iron-sulphur cluster biogenesis and mitochondrial iron homeostasis. Nat. Rev. Mol. Cell Biol. 6:345-351.
106. Wysong DR, Christin L, Sugar AM, Robbins PW, Diamond RD. 1998. Cloning and sequencing of a Candida albicans catalase gene and effects of disruption of this gene. Infect Immun 66:1953-1961.
107. Tripathi G, Wiltshire C, Macaskill S, Tournu H, Budge S, Brown AJP. 2002. Gcn4 co-ordinates morphogenetic and metabolic responses to amino acid starvation in Candida albicans. EMBO J 21:5448-5456.
108. Bullen JJ, Rogers HJ, Spalding PB, Ward CG. 2006. Natural resistance, iron and infection: a challenge for clinical medicine. J Med Microbiol 55:251-258.
109. Heitman J, Movva NR, Hall MN. 1991. Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast. Science 253:905-909.
110. Rohde JR, Bastidas R, Puria R, Cardenas ME. 2008. Nutritional control via Tor signaling in Saccharomyces cerevisiae. Curr Opin Microbiol 11:153-160.
111. Cardenas ME, Cutler NS, Lorenz MC, Di Como CJ, Heitman J. 1999. The TOR signaling cascade regulates gene expression in response to nutrients. Genes Dev 13:3271-3279.
112. Bastidas RJ, Heitman J, Cardenas ME. 2009. The protein kinase Tor1 regulates adhesin gene expression in Candida albicans. PLoS Pathog 5:e1000294.
113. Cruz MC, Goldstein AL, Blankenship J, Del Poeta M, Perfect JR, McCusker JH, Bennani YL, Cardenas ME, Heitman J. 2001. Rapamycin and less immunosuppressive analogs are toxic to Candida albicans and Cryptococcus neoformans via FKBP12-dependent inhibition of TOR. Antimicrobial agents and chemotherapy 45:3162-3170.
114. Biswas K, Morschhauser J. 2005. The Mep2p ammonium permease controls nitrogen starvation-induced filamentous growth in Candida albicans. Mol Microbiol 56:649-669.
115. Dabas N, Schneider S, Morschhauser J. 2009. Mutational analysis of the Candida albicans ammonium permease Mep2p reveals residues required for ammonium transport and signaling. Eukaryot Cell 8:147-160.
116. Howard DH. 1999. Acquisition, transport, and storage of iron by pathogenic fungi. Clin Microbiol Rev 12:394-404.
117. Howard DH. 2004. Iron gathering by zoopathogenic fungi. FEMS Immunol Med Microbiol 40:95-100.
118. Sutak R, Lesuisse E, Tachezy J, Richardson DR. 2008. Crusade for iron: iron uptake in unicellular eukaryotes and its significance for virulence. Trends Microbiol 16:261-268.
119. Ibrahim AS, Edwards JE, Jr., Fu Y, Spellberg B. 2006. Deferiprone iron chelation as a novel therapy for experimental mucormycosis. J Antimicrob Chemother 58:1070-1073.
120. Ibrahim AS, Spellberg B, Edwards J, Jr. 2008. Iron acquisition: a novel perspective on mucormycosis pathogenesis and treatment. Curr Opin Infect Dis 21:620-625.
121. Ibrahim AS, Gebermariam T, Fu Y, Lin L, Husseiny MI, French SW, Schwartz J, Skory CD, Edwards JE, Jr., Spellberg BJ. 2007. The iron chelator deferasirox protects mice from mucormycosis through iron starvation. J Clin Invest 117:2649-2657.
122. Ibrahim AS, Gebremariam T, French SW, Edwards JE, Jr., Spellberg B. 2010. The iron chelator deferasirox enhances liposomal amphotericin B efficacy in treating murine invasive pulmonary aspergillosis. J Antimicrob Chemother 65:289-292.
123. Heymann P, Gerads M, Schaller M, Dromer F, Winkelmann G, Ernst JF. 2002. The siderophore iron transporter of Candida albicans (Sit1p/Arn1p) mediates uptake of ferrichrome-type siderophores and is required for epithelial invasion. Infect Immun 70:5246-5255.
124. Hissen AH, Wan AN, Warwas ML, Pinto LJ, Moore MM. 2005. The Aspergillus fumigatus siderophore biosynthetic gene sidA, encoding L-ornithine N5-oxygenase, is required for virulence. Infect Immun 73:5493-5503.
125. Schrettl M, Bignell E, Kragl C, Joechl C, Rogers T, Arst HN, Jr., Haynes K, Haas H. 2004. Siderophore biosynthesis but not reductive iron assimilation is essential for Aspergillus fumigatus virulence. J Exp Med 200:1213-1219.
126. Jung WH, Sham A, White R, Kronstad JW. 2006. Iron regulation of the major virulence factors in the AIDS-associated pathogen Cryptococcus neoformans. PLoS Biol 4:e410.
127. Schrettl M, Beckmann N, Varga J, Heinekamp T, Jacobsen ID, Jochl C, Moussa TA, Wang S, Gsaller F, Blatzer M, Werner ER, Niermann WC, Brakhage AA, Haas H. 2010. HapX-mediated adaption to iron starvation is crucial for virulence of Aspergillus fumigatus. PLoS Pathog 6.
128. Gross L. 2006. Iron Regulation and an Opportunistic AIDS-Related Fungal Infection. PLoS Biol 4:e427.
129. da Silva Neto JF, Braz VS, Italiani VC, Marques MV. 2009. Fur controls iron homeostasis and oxidative stress defense in the oligotrophic alpha-proteobacterium Caulobacter crescentus. Nucleic Acids Res 37:4812-4825.
130. Huang DL, Tang DJ, Liao Q, Li HC, Chen Q, He YQ, Feng JX, Jiang BL, Lu GT, Chen B, Tang JL. 2008. The Zur of Xanthomonas campestris functions as a repressor and an activator of putative zinc homeostasis genes via recognizing two distinct sequences within its target promoters. Nucleic Acids Res 36:4295-4309.
131. Mercier A, Labbe S. 2009. Both Php4 function and subcellular localization are regulated by iron via a multistep mechanism involving the glutaredoxin Grx4 and the exportin Crm1. J Biol Chem 284:20249-20262.
132. Pujol-Carrion N, Belli G, Herrero E, Nogues A, de la Torre-Ruiz MA. 2006. Glutaredoxins Grx3 and Grx4 regulate nuclear localisation of Aft1 and the oxidative stress response in Saccharomyces cerevisiae. J Cell Sci 119:4554-4564.
133. Ojeda L, Keller G, Muhlenhoff U, Rutherford JC, Lill R, Winge DR. 2006. Role of glutaredoxin-3 and glutaredoxin-4 in the iron regulation of the Aft1 transcriptional activator in Saccharomyces cerevisiae. J Biol Chem 281:17661-17669.
134. Demain AL. 1972. Riboflavin oversynthesis. Annu Rev Microbiol 26:369-388.
135. Fedorovich D, Protchenko O, Lesuisse E. 1999. Iron uptake by the yeast Pichia guilliermondii. Flavinogenesis and reductive iron assimilation are co-regulated processes. Biometals 12:295-300.
136. Boretsky YR, Kapustyak KY, Fayura LR, Stasyk OV, Stenchuk MM, Bobak YP, Drobot LB, Sibirny AA. 2005. Positive selection of mutants defective in transcriptional repression of riboflavin synthesis by iron in the flavinogenic yeast Pichia guilliermondii. FEMS Yeast Res 5:829-837.
137. Pynyaha YV, Boretsky YR, Fedorovych DV, Fayura LR, Levkiv AI, Ubiyvovk VM, Protchenko OV, Philpott CC, Sibirny AA. 2009. Deficiency in frataxin homologue YFH1 in the yeast Pichia guilliermondii leads to missregulation of iron acquisition and riboflavin biosynthesis and affects sulfate assimilation. Biometals.
138. Coves J, Fontecave M. 1993. Reduction and mobilization of iron by a NAD(P)H:flavin oxidoreductase from Escherichia coli. Eur J Biochem 211:635-641.
139. von Canstein H, Ogawa J, Shimizu S, Lloyd JR. 2008. Secretion of flavins by Shewanella species and their role in extracellular electron transfer. Appl Environ Microbiol 74:615-623.
140. Wang L, Chi Z, Wang X, Ju L, Guo N. 2008. Isolation and characterization of Candida membranifaciens subsp. flavinogenie W14-3, a novel riboflavin-producing marine yeast. Microbiol Res 163:255-266.
141. Yatsyshyn VY, Ishchuk OP, Voronovsky AY, Fedorovych DV, Sibirny AA. 2009. Production of flavin mononucleotide by metabolically engineered yeast Candida famata. Metab Eng 11:163-167.
142. Braun BR, Johnson AD. 1997. Control of filament formation in Candida albicans by the transcriptional repressor TUP1. Science 277:105-109.
143. Zhao R, Lockhart SR, Daniels K, Soll DR. 2002. Roles of TUP1 in switching, phase maintenance, and phase-specific gene expression in Candida albicans. Eukaryot Cell 1:353-365.
144. Park YN, Morschhauser J. 2005. Candida albicans MTLalpha tup1Delta mutants can reversibly switch to mating-competent, filamentous growth forms. Mol Microbiol 58:1288-1302.
145. Murad AM, d'Enfert C, Gaillardin C, Tournu H, Tekaia F, Talibi D, Marechal D, Marchais V, Cottin J, Brown AJ. 2001. Transcript profiling in Candida albicans reveals new cellular functions for the transcriptional repressors CaTup1, CaMig1 and CaNrg1. Mol Microbiol 42:981-993.
146. Palmer GE, Johnson KJ, Ghosh S, Sturtevant J. 2004. Mutant alleles of the essential 14-3-3 gene in Candida albicans distinguish between growth and filamentation. Microbiology 150:1911-1924.
147. Cleary IA, MacGregor NB, Saville SP, Thomas DP. 2012. Investigating the function of Ddr48p in Candida albicans. Eukaryot Cell 11:718-724.
148. Liao WL, Ramon AM, Fonzi WA. 2008. GLN3 encodes a global regulator of nitrogen metabolism and virulence of C. albicans. Fungal genetics and biology : FG & B 45:514-526.
149. Zacchi LF, Gomez-Raja J, Davis DA. 2010. Mds3 regulates morphogenesis in Candida albicans through the TOR pathway. Mol Cell Biol 30:3695-3710.
150. Neuhauser B, Dunkel N, Satheesh SV, Morschhauser J. 2011. Role of the Npr1 kinase in ammonium transport and signaling by the ammonium permease Mep2 in Candida albicans. Eukaryot Cell 10:332-342.
151. MacGurn JA, Hsu PC, Smolka MB, Emr SD. 2011. TORC1 regulates endocytosis via Npr1-mediated phosphoinhibition of a ubiquitin ligase adaptor. Cell 147:1104-1117.
152. van Burik JA, Magee PT. 2001. Aspects of fungal pathogenesis in humans. Annu Rev Microbiol 55:743-772.
153. Cutler JE. 1991. Putative virulence factors of Candida albicans. Annu Rev Microbiol 45:187-218.
154. Hogan LH, Klein BS, Levitz SM. 1996. Virulence factors of medically important fungi. Clin Microbiol Rev 9:469-488.
155. Mavor AL, Thewes S, Hube B. 2005. Systemic fungal infections caused by Candida species: epidemiology, infection process and virulence attributes. Current drug targets 6:863-874.
156. Khan MS, Ahmad I, Aqil F, Owais M, Shahid M, Musarrat J. 2010. Virulence and Pathogenicity of Fungal Pathogens with Special Reference to Candida albicans, p. 21-45. In Ahmad I, SpringerLink (Online service) (ed.), Combating fungal infections problems and remedy. Springer-Verlag Berlin Heidelberg, Berlin, Heidelberg.
157. Chandra J, Kuhn DM, Mukherjee PK, Hoyer LL, McCormick T, Ghannoum MA. 2001. Biofilm formation by the fungal pathogen Candida albicans: development, architecture, and drug resistance. J Bacteriol 183:5385-5394.
158. Fradin C, Kretschmar M, Nichterlein T, Gaillardin C, d'Enfert C, Hube B. 2003. Stage-specific gene expression of Candida albicans in human blood. Mol Microbiol 47:1523-1543.
159. Fu Y, Ibrahim AS, Sheppard DC, Chen YC, French SW, Cutler JE, Filler SG, Edwards JE, Jr. 2002. Candida albicans Als1p: an adhesin that is a downstream effector of the EFG1 filamentation pathway. Mol Microbiol 44:61-72.
160. Gaur NK, Klotz SA, Henderson RL. 1999. Overexpression of the Candida albicans ALA1 gene in Saccharomyces cerevisiae results in aggregation following attachment of yeast cells to extracellular matrix proteins, adherence properties similar to those of Candida albicans. Infect Immun 67:6040-6047.
161. Perier RC, Praz V, Junier T, Bonnard C, Bucher P. 2000. The eukaryotic promoter database (EPD). Nucleic Acids Res 28:302-303.
162. Currie RA. 1998. NF-Y is associated with the histone acetyltransferases GCN5 and P/CAF. J Biol Chem 273:1430-1434.
163. Li Q, Herrler M, Landsberger N, Kaludov N, Ogryzko VV, Nakatani Y, Wolffe AP. 1998. Xenopus NF-Y pre-sets chromatin to potentiate p300 and acetylation-responsive transcription from the Xenopus hsp70 promoter in vivo. EMBO J 17:6300-6315.
164. Faniello MC, Bevilacqua MA, Condorelli G, de Crombrugghe B, Maity SN, Avvedimento VE, Cimino F, Costanzo F. 1999. The B subunit of the CAAT-binding factor NFY binds the central segment of the Co-activator p300. J Biol Chem 274:7623-7626.
165. Zhu J, Giannola DM, Zhang Y, Rivera AJ, Emerson SG. 2003. NF-Y cooperates with USF1/2 to induce the hematopoietic expression of HOXB4. Blood 102:2420-2427.
166. Benatti P, Basile V, Merico D, Fantoni LI, Tagliafico E, Imbriano C. 2008. A balance between NF-Y and p53 governs the pro- and anti-apoptotic transcriptional response. Nucleic Acids Res 36:1415-1428.
167. Dabas N, Morschhauser J. 2007. Control of ammonium permease expression and filamentous growth by the GATA transcription factors GLN3 and GAT1 in Candida albicans. Eukaryot Cell 6:875-888.
168. Dabas N, Morschhauser J. 2008. A transcription factor regulatory cascade controls secreted aspartic protease expression in Candida albicans. Mol Microbiol 69:586-602.
169. Kato M. 2005. An overview of the CCAAT-box binding factor in filamentous fungi: assembly, nuclear translocation, and transcriptional enhancement. Bioscience, biotechnology, and biochemistry 69:663-672.
170. Harbison CT, Gordon DB, Lee TI, Rinaldi NJ, Macisaac KD, Danford TW, Hannett NM, Tagne JB, Reynolds DB, Yoo J, Jennings EG, Zeitlinger J, Pokholok DK, Kellis M, Rolfe PA, Takusagawa KT, Lander ES, Gifford DK, Fraenkel E, Young RA. 2004. Transcriptional regulatory code of a eukaryotic genome. Nature 431:99-104.
171. Zaman S, Lippman SI, Zhao X, Broach JR. 2008. How Saccharomyces responds to nutrients. Annual review of genetics 42:27-81.
172. De Virgilio C, Loewith R. 2006. Cell growth control: little eukaryotes make big contributions. Oncogene 25:6392-6415.
173. Loewith R, Hall MN. 2011. Target of rapamycin (TOR) in nutrient signaling and growth control. Genetics 189:1177-1201.
174. Kim J, Guan KL. 2011. Amino acid signaling in TOR activation. Annual review of biochemistry 80:1001-1032.
175. Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, Valentin F, Wallace IM, Wilm A, Lopez R, Thompson JD, Gibson TJ, Higgins DG. 2007. Clustal W and Clustal X version 2.0. Bioinformatics 23:2947-2948.
176. Gillum AM, Tsay EYH, Kirsch DR. 1984. Isolation of the Candida albicans gene for orotidine-5′-phosphate decarboxylase by complementation of S. cerevisiae ura3 and E. coli pyrF mutations. Molecular and General Genetics MGG 198:179-182.
177. Braun BR, Johnson AD. 2000. TUP1, CPH1 and EFG1 make independent contributions to filamentation in candida albicans. Genetics 155:57-67.
178. Staib P, Lermann U, Blass-Warmuth J, Degel B, Wurzner R, Monod M, Schirmeister T, Morschhauser J. 2008. Tetracycline-inducible expression of individual secreted aspartic proteases in Candida albicans allows isoenzyme-specific inhibitor screening. Antimicrobial agents and chemotherapy 52:146-156.
179. Fonzi WA, Irwin MY. 1993. Isogenic Strain Construction and Gene Mapping in Candida albicans. Genetics 134:717-728.
180. Goujon M, McWilliam H, Li W, Valentin F, Squizzato S, Paern J, Lopez R. 2010. A new bioinformatics analysis tools framework at EMBL-EBI. Nucleic Acids Res 38:W695-699.

全文公開日期本全文未授權公開 (校內網路)
全文公開日期本全文未授權公開 (校外網路)

簡易檢索 / 詳目顯示

相關論文