title: The Stress-Activated Signaling (SAS) Pathways of a Human Fungal Pathogen, Cryptococcus neoformans.
abstract: Cryptococcus neoformans is a basidiomycete human fungal pathogen that causes meningoencephalitis in both immunocompromised and immunocompetent individuals. The ability to sense and respond to diverse extracellular signals is essential for the pathogen to infect and cause disease in the host. Four major stress-activated signaling (SAS) pathways have been characterized in C. neoformans, including the HOG (high osmolarity glycerol response), PKC/Mpk1 MAPK (mitogen-activated protein kinase), calcium-dependent calcineurin, and RAS signaling pathways. The HOG pathway in C. neoformans not only controls responses to diverse environmental stresses, including osmotic shock, UV irradiation, oxidative stress, heavy metal stress, antifungal drugs, toxic metabolites, and high temperature, but also regulates ergosterol biosynthesis. The PKC (Protein kinase C)/Mpk1 pathway in C. neoformans is involved in a variety of stress responses, including osmotic, oxidative, and nitrosative stresses and breaches of cell wall integrity. The Ca(2+)/calmodulin- and Ras-signaling pathways also play critical roles in adaptation to certain environmental stresses, such as high temperature and sexual differentiation. Perturbation of the SAS pathways not only impairs the ability of C. neoformans to resist a variety of environmental stresses during host infection, but also affects production of virulence factors, such as capsule and melanin. A drug(s) capable of targeting signaling components of the SAS pathway will be effective for treatment of cryptococcosis.
authors: Department of Biotechnology, Center for Fungal Pathogenesis, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
authors: Kwang-Woo
authors: KW
authors: Jung
authors: Yong-Sun
authors: YS
authors: Bahn
keywords: Cryptococcus neoformans; Human fungal pathogens; SAS pathways; Signaling; Stress-response
references: Cell. 1990 Jul 27;62(2):213-24
references: 2196995
references: Mol Biol Cell. 2001 Jun;12(6):1541-55
references: 11408567
references: Microbiology (Reading). 2002 Jan;148(Pt 1):191-201
references: 11782511
references: J Infect Dis. 1993 Jan;167(1):186-90
references: 8418165
references: FEMS Yeast Res. 2004 Oct;5(1):1-10
references: 15381117
references: J Bacteriol. 1982 Jun;150(3):1414-21
references: 6804444
references: Eukaryot Cell. 2005 Jan;4(1):190-201
references: 15643074
references: Appl Environ Microbiol. 1994 Oct;60(10):3864-6
references: 7986054
references: Mycologia. 1976 Jul-Aug;68(4):821-33
references: 790172
references: Eukaryot Cell. 2009 Aug;8(8):1197-217
references: 19542307
references: Genetics. 2002 Feb;160(2):463-70
references: 11861553
references: EMBO J. 1997 May 15;16(10):2576-89
references: 9184205
references: Infect Immun. 1995 Aug;63(8):3131-6
references: 7622240
references: Cell Biochem Biophys. 1999;30(1):115-51
references: 10099825
references: FEMS Microbiol Lett. 1997 Aug 15;153(2):265-72
references: 9271852
references: Yeast. 1994 Dec;10(13):1753-90
references: 7747517
references: J Med Microbiol. 2004 Sep;53(Pt 9):935-940
references: 15314203
references: EMBO J. 1992 Apr;11(4):1391-5
references: 1563351
references: Infect Immun. 1997 May;65(5):1584-92
references: 9125534
references: Mol Biol Evol. 2008 Mar;25(3):507-16
references: 18187560
references: Microbiology (Reading). 2006 Mar;152(Pt 3):591-604
references: 16514140
references: Infect Immun. 2005 Aug;73(8):4922-33
references: 16041006
references: Fungal Genet Biol. 2003 Feb;38(1):110-21
references: 12553941
references: Infect Immun. 1992 May;60(5):1869-74
references: 1563776
references: Biochim Biophys Acta. 2007 Aug;1773(8):1311-40
references: 17604854
references: Eukaryot Cell. 2002 Feb;1(1):75-84
references: 12455973
references: Cell. 2004 Aug 6;118(3):351-61
references: 15294160
references: Infect Immun. 1998 May;66(5):2230-6
references: 9573112
references: Mol Cell Biol. 2001 May;21(9):3179-91
references: 11287622
references: Nature. 1990 Nov 8;348(6297):125-32
references: 2122258
references: Nat Rev Microbiol. 2005 Oct;3(10):753-64
references: 16132036
references: Cell. 1984 Jun;37(2):437-45
references: 6327067
references: Nature. 1991 Jan 10;349(6305):117-27
references: 1898771
references: Antimicrob Agents Chemother. 2000 Mar;44(3):739-46
references: 10681348
references: J Biol Chem. 2004 May 14;279(20):21144-53
references: 15014071
references: Med Mycol. 1998 Dec;36(6):419-24
references: 10206753
references: Mol Microbiol. 2007 Feb;63(4):1118-30
references: 17233829
references: Curr Top Cell Regul. 2000;36:237-95
references: 10842755
references: Nature. 2005 Apr 21;434(7036):1017-21
references: 15846346
references: Infect Immun. 1999 Oct;67(10):5477-9
references: 10496933
references: Bioessays. 2002 Oct;24(10):894-903
references: 12325122
references: Microbiology (Reading). 2000 Aug;146 ( Pt 8):1763-1774
references: 10931884
references: Trends Biochem Sci. 1996 Jan;21(1):14-7
references: 8848832
references: Mol Microbiol. 2001 Feb;39(4):835-49
references: 11251806
references: Eukaryot Cell. 2008 Dec;7(12):2017-36
references: 18952900
references: Eukaryot Cell. 2003 Oct;2(5):1036-45
references: 14555486
references: Mol Microbiol. 2005 Oct;58(2):393-408
references: 16194228
references: EMBO J. 2007 Jul 11;26(13):3098-108
references: 17568771
references: Annu Rev Genet. 2001;35:647-72
references: 11700296
references: Eukaryot Cell. 2004 Dec;3(6):1476-91
references: 15590822
references: Trends Cell Biol. 2000 Aug;10(8):322-8
references: 10884684
references: Mol Cell Biol. 1999 Nov;19(11):7529-38
references: 10523641
references: Biochemistry. 1996 Jan 16;35(2):562-6
references: 8555228
references: Mol Biol Cell. 2006 Jul;17(7):3122-35
references: 16672377
references: J Bacteriol. 1999 Sep;181(18):5636-43
references: 10482503
references: Cell. 1992 Mar 20;68(6):1077-90
references: 1547504
references: Biochem Biophys Res Commun. 2003 Nov 28;311(4):1151-7
references: 14623301
references: Infect Immun. 1996 Jun;64(6):1977-83
references: 8675296
references: J Bacteriol. 1991 Jan;173(1):401-3
references: 1898925
references: Mol Cell Biol. 1994 Jul;14(7):4912-9
references: 8007987
references: Gene. 1995 Dec 29;167(1-2):179-83
references: 8566774
references: Cell. 1985 Jan;40(1):27-36
references: 2981630
references: Infect Immun. 1986 Jan;51(1):218-23
references: 3079732
references: Semin Cell Biol. 1995 Apr;6(2):89-94
references: 7548847
references: Nat Rev Mol Cell Biol. 2003 Jul;4(7):517-29
references: 12838335
references: Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7327-31
references: 8692992
references: Eukaryot Cell. 2008 Oct;7(10):1685-98
references: 18689526
references: Eukaryot Cell. 2005 Jun;4(6):1079-87
references: 15947200
references: Genes Dev. 1997 Dec 1;11(23):3206-17
references: 9389652
references: Microbiol Mol Biol Rev. 2005 Jun;69(2):262-91
references: 15944456
references: Eukaryot Cell. 2009 Mar;8(3):315-26
references: 19151325
references: Eukaryot Cell. 2007 Dec;6(12):2278-89
references: 17951522
references: Am J Epidemiol. 1978 Oct;108(4):337-40
references: 364979
references: Infect Immun. 2001 Sep;69(9):5589-96
references: 11500433
references: Annu Rev Microbiol. 2006;60:69-105
references: 16704346
references: Nature. 1984 Jun 7-13;309(5968):523-7
references: 6328319
references: Cell. 1991 Aug 23;66(4):807-15
references: 1715244
references: Fungal Genet Biol. 2003 Aug;39(3):230-7
references: 12892636
references: Annu Rev Biochem. 1987;56:779-827
references: 3304147
references: Infect Immun. 2003 Nov;71(11):6155-64
references: 14573631
references: Mol Microbiol. 2000 Apr;36(2):352-65
references: 10792722
references: Mol Biol Cell. 2005 May;16(5):2285-300
references: 15728721
references: Mol Microbiol. 2003 Nov;50(4):1401-9
references: 14622425
references: EMBO J. 1998 Dec 1;17(23):6942-51
references: 9843500
references: Life Sci Space Res. 1973;11:55-61
references: 12523380
references: J Cell Biol. 1999 Oct 4;147(1):163-74
references: 10508863