The (patho)physiological functions of the MRP family

The identification of certain members of the large superfamily of ATP binding cassette transport proteins such as MDRI-P-glycoprotein and the multidrug resistance protein MRPI 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 MDR I, MRPI mainly transports anionic Phase Il-conjugates. In addition MRP I-mediated drug resistance is highly dependent on high intracellular glutathione levels which may be linked to the apparent physiological involvement of MRPI in glutathione-related cellular processes. This review summarizes the current knowledge about functional aspects of MRPI and its five recently cloned homologues MRP2-MRP6 and discusses their substrate specificities and cellular localization with emphasis on drug resistance. (C) 2000 Harcourt Publishers Ltd.