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Multidrug resistance mediated by the ATP‐binding cassette transporter protein MRP
Author(s) -
Cole Susan P.C.,
Deeley Roger G.
Publication year - 1998
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/(sici)1521-1878(199811)20:11<931::aid-bies8>3.0.co;2-j
Subject(s) - atp binding cassette transporter , glutathione , multidrug resistance associated proteins , p glycoprotein , biochemistry , transporter , multiple drug resistance , leukotriene c4 , transport protein , biology , chemistry , gene , leukotriene , enzyme , asthma , immunology , antibiotics
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. BioEssays 20:931–940, 1998. © 1998 John Wiley & Sons, Inc.