Hsp90 potentiates the rapid evotution of new traits: Drug resistance in diverse fungi

被引:525
作者
Cowen, LE [1 ]
Lindquist, S [1 ]
机构
[1] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA
关键词
D O I
10.1126/science.1118370
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Hsp90 is a molecular chaperone for many signal transducers and may influence evolution by releasing previously silent genetic variation in response to environmental change. In fungi separated by similar to 800 million years of evolution, Hsp90 potentiated the evolution of drug resistance in a different way, by enabling new mutations' to have immediate phenotypic consequences. Resistance was abrogated by Hsp90 inhibitors and by febrile temperatures, suggesting new therapeutic strategies and a clinical benefit of fever. During selection in a human host, drug resistance that was initially Hsp90-dependent evolved toward independence. Thus, Hsp90 can act in diverse ways to couple environmental contingency to the emergence and fixation of new traits.
引用
收藏
页码:2185 / 2189
页数:5
相关论文
共 37 条
[1]   Haploidy, diploidy and evolution of antifungal drug resistance in Saccharomyces cerevisiae [J].
Anderson, JB ;
Sirjusingh, C ;
Ricker, N .
GENETICS, 2004, 168 (04) :1915-1923
[2]  
Anderson JB, 2003, GENETICS, V163, P1287
[3]  
Bagatell R, 2004, MOL CANCER THER, V3, P1021
[4]   Evolutionary capacitance as a general feature of complex gene networks [J].
Bergman, A ;
Siegal, ML .
NATURE, 2003, 424 (6948) :549-552
[5]  
Blankenship Jill R, 2003, Curr Opin Investig Drugs, V4, P192
[6]   Evolution of drug resistance in Candida albicans [J].
Cowen, LE ;
Anderson, JB ;
Kohn, LM .
ANNUAL REVIEW OF MICROBIOLOGY, 2002, 56 :139-165
[7]  
COWEN LE, UNPUB
[8]   Calcineurin is essential for survival during membrane stress in Candida albicans [J].
Cruz, MC ;
Goldstein, AL ;
Blankenship, JR ;
Del Poeta, M ;
Davis, D ;
Cardenas, ME ;
Perfect, JR ;
McCusker, JH ;
Heitman, J .
EMBO JOURNAL, 2002, 21 (04) :546-559
[9]   Oncogenic mutations reduce the stability of Src kinase [J].
Falsone, SF ;
Leptihn, S ;
Osterauer, A ;
Haslbeck, M ;
Buchner, J .
JOURNAL OF MOLECULAR BIOLOGY, 2004, 344 (01) :281-291
[10]   Good fungi gone bad: the corruption of calcineurin [J].
Fox, DS ;
Heitman, J .
BIOESSAYS, 2002, 24 (10) :894-903