Isolation of MOAT-B, a widely expressed multidrug resistance-associated protein/canalicular multispecific organic anion transporter-related transporter

Kun Lee, Martin G. Belinsky, Daphne W. Bell, Joseph R. Testa, Gary D. Kruh

Research output: Contribution to journalArticlepeer-review

140 Scopus citations

Abstract

Multidrug resistance-associated protein (MRP) and canalicular multi- specific organic anion transporter (cMOAT) are closely related mammalian ATP- binding cassette transporters that export organic anions from ells. Transfection studies have established that MRP confers resistance to natural product cytotoxic agents, and recent evidence suggests the possibility that cMOAT may contribute to cytotoxic drug resistance as well. Based upon the potential importance of these transporters in clinical drug resistance and their important physiological roles in the export of the amphiphilic products of phase I and phase II metabolism, we sought to identify other MRP-related transporters. Using a degenerate PCR approach, we isolated a cDNA that encodes a novel ATP-binding cassette transporter, which we designated MOAT- B. The MOAT-B gene was mapped using fluorescence in situ hybridization to chromosome band 13q32. Comparison of the MOAT-B predicted protein with other transporters revealed that it is most closely related to MRP, cMOAT, and the yeast organic anion transporter YCF1. Although MOAT-B is closely related to these transporters, it is distinguished by the absence of a ~200 amino acid NH2-terminal hydrophobic extension that is present in MRP and cMOAT and which is predicted to encode several transmembrane spanning segments. In addition, the MOAT-B tissue distribution is distinct from MRP and cMOAT. In contrast to MRP, which is widely expressed in tissues, including liver, and cMOAT, the expression of which is largely restricted to liver, the MOAT-B transcript is widely expressed, with particularly high levels in prostate, but is barely detectable in liver. These data indicate that MOAT-B is a ubiquitously expressed transporter that is closely related to MRP and cMOAT and raise the possibility that it may be an organic anion pump relevant to cellular detoxification.

Original languageEnglish
Pages (from-to)2741-2747
Number of pages7
JournalCancer Research
Volume58
Issue number13
StatePublished - Jul 1 1998

Keywords

  • ATP Binding Cassette Transporter, Subfamily B, Member 1/chemistry
  • Amino Acid Sequence
  • Anion Transport Proteins
  • Base Sequence
  • Carrier Proteins/chemistry
  • Chromosome Mapping
  • Chromosomes, Human, Pair 13/genetics
  • Drug Resistance, Multiple/genetics
  • Humans
  • Molecular Sequence Data

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