Multidrug resistance mediated by the ATP-binding cassette transporter protein MRP

Bioessays. 1998 Nov;20(11):931-40. doi: 10.1002/(SICI)1521-1878(199811)20:11<931::AID-BIES8>3.0.CO;2-J.


Resistance to multiple natural product drugs associated with reduced drug accumulation in human tumor cells may be conferred by either the 170 kDa P-glycoprotein or the 190 kDa multidrug resistance protein, MRP. Both MRP and P-glycoprotein belong to the large and ancient ATP-binding cassette (ABC) superfamily of transport proteins but share only 15% amino acid identify. Unlike P-glycoprotein, MRP actively transports conjugated organic anions such as the cysteinyl leukotriene C4 and glutathione-conjugated aflatoxin B1. Transport of unconjugated chemotherapeutic agents appears to require cotransport of glutathione. MRP and several more recently discovered ABC proteins contain an additional NH2-proximal membrane-spanning domain not found in previously characterized ABC transporters. This domain, whose NH2-terminus is extracytosolic, is essential for MRP-mediated transport activity. This review summarizes current knowledge of the structural and transport characteristics of MRP which suggest that the physiologic functions of this protein could range from a protective role in chemical toxicity and oxidative stress to mediation of inflammatory responses involving cysteinyl leukotrienes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • ATP-Binding Cassette Transporters / chemistry
  • ATP-Binding Cassette Transporters / metabolism*
  • Animals
  • Antineoplastic Agents / pharmacokinetics*
  • Biological Transport
  • Cell Membrane / metabolism
  • Cell Membrane / ultrastructure
  • Drug Resistance, Multiple*
  • Humans
  • Models, Molecular
  • Multidrug Resistance-Associated Proteins
  • Protein Structure, Secondary
  • Tumor Cells, Cultured


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP-Binding Cassette Transporters
  • Antineoplastic Agents
  • Multidrug Resistance-Associated Proteins