ERG6 and PDR5 regulate small lipophilic drug accumulation in yeast cells via distinct mechanisms
ERG6 and PDR5 regulate small lipophilic drug accumulation in yeast cells via distinct mechanisms
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DOI：
10.1016/s0014-5793(02)02818-1
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发表时间：
2002-06-19
期刊：
影响因子：
3.5
通讯作者：
Kralli, A
中科院分区：
文献类型：
--
作者：
Emter, R;Heese-Peck, A;Kralli, A
多药耐药性的诊断和规避需要了解潜在的细胞机制。在模型生物酿酒酵母中，PDR5 或 ERG6 的缺失增加了对许多小亲脂性药物的敏感性。 Pdr5p 是一种质膜 ATP 结合盒转运蛋白，可主动输出药物，从而降低其细胞内水平。 ERG6（甾醇生物合成中的一种酶）影响药物蓄积的机制尚不清楚。我们在此表明，ERG6 限制了被动药物跨膜扩散的速率，而不影响 Pdr5p 介导的药物输出。与其通过不同机制发挥作用一致，PDR5 和 ERG6 对药物蓄积的影响是相加的。 (C) 2002 年由 Elsevier Science B.V. 代表欧洲生化学会联合会出版。
Diagnosis and circumvention of multi-drug resistance requires an understanding of the underlying cellular mechanisms. In the model organism Saccharomyces cerevisiae, deletions of PDR5 or ERG6 increase sensitivity to many small lipophilic drugs. Pdr5p is a plasma membrane ATP-binding cassette transporter that actively exports drugs, thereby lowering their intracellular levels. The mechanism by which ERG6, an enzyme in sterol biosynthesis, affects drug accumulation is less clear. We show here that ERG6 limits the rate of passive drug diffusion across the membrane, without affecting Pdr5p-mediated drug export. Consistent with their action by distinct mechanisms, PDR5 and ERG6 effects on drug accumulation are additive. (C) 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.