Multidrug resistance associated proteins in multidrug resistance

Abstract

Multidrug resistance proteins (MRPs) are members of the C family of a group of proteins named ATP-binding cassette (ABC) transporters. These ABC transporters together form the largest branch of proteins within the human body. The MRP family comprises of 13 members, of which MRP1 to MRP9 are the major transporters indicated to cause multidrug resistance in tumor cells by extruding anticancer drugs out of the cell. They are mainly lipophilic anionic transporters and are reported to transport free or conjugates of glutathione (GSH), glucuronate, or sulphate. In addition, MRP1 to MRP3 can transport neutral organic drugs in free form in the presence of free GSH. Collectively, MRPs can transport drugs that differ structurally and mechanistically, including natural anticancer drugs, nucleoside analogs, antimetabolites, and tyrosine kinase inhibitors. Many of these MRPs transport physiologically important anions such as leukotriene C4, bilirubin glucuronide, and cyclic nucleotides. This review focuses mainly on the physiological functions, cellular resistance characteristics, and probable in vivo role of MRP1 to MRP9.

Figure 1.. The pictorial depiction shows the topography and the location of both the short- (MRP4, MRP5, MRP6, MRP8 and MRP9) and long-form (MRP1, MRP2, MRP3, and MRP7) members of the MRP subfamily.

Each of these transporters pumps out a variety of endogenous and xenobiotic substrates. These transporters are mainly present either apically or basolateraly; however, the localization of MRP7 and MRP9 is still unknown. The substrates of MRP9, the last member to be cloned among the MRP subfamily, are still unknown and are open for discussion. MRP, multidrug resistance protein.