Multidrug resistance-associated protein 1 (MRP1/ABCC1) polymorphism: from discovery to clinical application - PubMed (original) (raw)

Review

Multidrug resistance-associated protein 1 (MRP1/ABCC1) polymorphism: from discovery to clinical application

Jiye Yin et al. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2011 Oct.

Abstract

Multidrug resistance-associated protein 1(MRP1/ABCC1) is the first identified member of ABCC subfamily which belongs to ATP-binding cassette (ABC) transporter superfamily. It is ubiquitously expressed in almost all human tissues and transports a wide spectrum of substrates including drugs, heavy metal anions, toxicants, and conjugates of glutathione, glucuronide and sulfate. With the advance of sequence technology, many MRP1/ABCC1 polymorphisms have been identified. Accumulating evidences show that some polymorphisms are significantly associated with drug resistance and disease susceptibility. In vitro reconstitution studies have also unveiled the mechanism for some polymorphisms. In this review, we present recent advances in understanding the role and mechanism of MRP1/ABCC1 polymorphisms in drug resistance, toxicity, disease susceptibility and severity, prognosis prediction, and Methods to select and predict functional polymorphisms.

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Figures

Fig. 1

A:Schematic representation of the topological structure of MRP1/ABCC1 protein predicted using TOPO2 program with modification (

http://www.sacs.ucsf.edu/TOPO-run/wtopo.pl

). The consensus sequences of Walker A and B are highlighted in orange and green, respectively. The ABC-signature motif is highlighted in red. TM, transmembrane; MSD, membrane spanning domain; NBD, nucleotide-binding domain. B: Distribution of clinically relevant MRP1/ABCC1 exon polymorphisms.

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