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

✍ Scribed by Susan P.C. Cole; Roger G. Deeley

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 203 KB
• Volume: 20
• Category: Article
• ISSN: 0265-9247
• DOI: 10.1002/(sici)1521-1878(199811)20:11<931::aid-bies8>3.0.co;2-j

✦ Synopsis

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 identity. Unlike P-glycoprotein, MRP actively transports conjugated organic anions such as the cysteinyl leukotriene C 4 and glutathione-conjugated aflatoxin B 1 . Transport of unconjugated chemotherapeutic agents appears to require cotransport of glutathione. MRP and several more recently discovered ABC proteins contain an additional NH 2 -proximal membrane-spanning domain not found in previously characterized ABC transporters. This domain, whose NH 2 -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.