Renes Johan, de Vries Elisabeth G. E., Jansen Peter L. M., Müller Michael
Groningen University Institute of Drug Exploration (GUIDE), Department of Gastroenterology, Hepatology, Department of Medical Oncology, University Hospital Groningen, Groningen, The Netherlands
Drug Resist Updat. 2000 Oct;3(5):289-302. doi: 10.1054/drup.2000.0156.
The identification of certain members of the large superfamily of ATP binding cassette transport proteins such as MDR1 -P-glycoprotein and the multidrug resistance protein MRP1 as ATP-dependent drug efflux pumps has been a major contribution in our understanding of the multidrug resistance phenotype of cancer cells. Importantly, both transport proteins that exhibit only low structural homology have a very different substrate specificity but confer resistance to a similar spectrum of natural product chemotherapeutic drugs. In contrast to the drug transporter MDR1, MRP1 mainly transports anionic Phase II-conjugates. In addition MRP1-mediated drug resistance is highly dependent on high intracellular glutathione levels which may be linked to the apparent physiological involvement of MRP1 in glutathione-related cellular processes. This review summarizes the current knowledge about functional aspects of MRP1 and its five recently cloned homologues MRP2-MRP6 and discusses their substrate specificities and cellular localization with emphasis on drug resistance. Copyright 2000 Harcourt Publishers Ltd.
某些ATP结合盒转运蛋白大家族成员的鉴定，如MDR1-P-糖蛋白和多药耐药蛋白MRP1作为ATP依赖性药物外排泵，对我们理解癌细胞的多药耐药表型有重大贡献。重要的是，这两种仅表现出低结构同源性的转运蛋白具有非常不同的底物特异性，但对相似范围的天然产物化疗药物具有耐药性。与药物转运蛋白MDR1不同，MRP1主要转运阴离子II相缀合物。此外，MRP1介导的耐药性高度依赖于细胞内高谷胱甘肽水平，这可能与MRP1在谷胱甘肽相关细胞过程中的明显生理参与有关。本综述总结了目前关于MRP1及其最近克隆的五个同源物MRP-2至MRP-6功能方面的知识，并讨论了它们的底物特异性和细胞定位，重点是耐药性。版权所有2000年哈考特出版有限公司。
