The (patho)physiological functions of the MRP family

Johan Renes, Elisabeth G. E. de Vries, Peter L. M. Jansen, Michael Müller

Research output: Contribution to journalArticlepeer-review

89 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)289-302
Number of pages14
JournalDrug Resistance Updates
Volume3
Issue number5
DOIs
Publication statusPublished - Oct 2000

Cite this