Hsp90 potentiates the rapid evotution of new traits: Drug resistance in diverse fungi
Hsp90 potentiates the rapid evotution of new traits: Drug resistance in diverse fungi
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DOI：
10.1126/science.1118370
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发表时间：
2005-09-30
期刊：
影响因子：
56.9
通讯作者：
Lindquist, S
中科院分区：
文献类型：
--
作者：
Cowen, LE;Lindquist, S
热休克蛋白90是许多信号转导分子的分子伴侣，并可能通过释放先前沉默的遗传变异来影响进化。在相隔近似8亿年进化的真菌中，Hsp90以不同的方式增强了耐药性的进化，使新的突变能够产生直接的表型后果。耐药性被Hsp90抑制剂和发热温度所消除，这表明新的治疗策略和发热的临床益处。在人类宿主的选择过程中，最初依赖Hsp90的耐药性逐渐向独立性发展。因此，热休克蛋白90可以以多种方式发挥作用，将环境偶然性与新性状的出现和固定结合起来。
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.