Multidrug Resistance-Associated Protein 2
Multidrug resistance-associated protein 2 [MRP2] or ATP-binding cassette sub-family C members 2 is a protein that in humans is programmed by the ABCC2 gene. The MRP2 is a known member of the ATP-binding cassette [ABC] transporters. ABC transporters are members of protein superfamily that is one of the largest and oldest in the families with members from extant phyla from prokaryotes to human beings. The term multidrug resistance has been used to elaborate the mechanism of resistance that cells [Eukaryotic and prokaryotic] have in response to the many chemotherapeutic drugs.
ABC proteins transport various molecules across extra and intra-cellular membranes. ABC genes are divided into seven unique subfamilies that include ABC1, MDR, TAP, MRP, GCN20, OABP and White. The ABC protein is a member of the MRP subfamily which is involved in multi-drug resistance. The protein is also exceptionally exhibited in the canalicular [apical] section of the hepatocyte and aids in biliary transport. The known substrate include anticancer drugs such as vinblastine. Thus, the multidrug resistance-associated protein 2 [MRP2] appears to contribute to drug resistance in mammalian cells.
Multidrug resistance-associated protein was incorporated into the drug resistance scene in 1992 when Susan Cole and Rodger Deeley cloned the Multidrug resistance-associated protein gene, the MRP1. The Multidrug resistance-associated protein 2 [MRP2] followed in 1996 and more MRP members followed. The MRP2 was characterized as the canalicular multispecific organic anion transporter [cMOAT] from its cloning. Homology is also high in MRP2 as it is in the Multidrug resistance-associated protein 1 [MRP1] 3 and 6. On top of this, these MRPs also share the characteristics of TMD0L0 segment. They are also seen in glutathione-drug conjugate [GS-X] and aid pump from eukaryotes like leishmania and yeast.
Within the ABC transporters in mammalians, the MRPs form a group that is clearly defined from the other known groups. MRP2 are able to transport methotrexate. MRP1,4 AND 5 RNAs are widely spread in the body while for MRP2, 3 and 6 mainly appear to function in kidney, liver and gut. While gathering more information on Multidrug resistance-associated proteins, there are a few problems encounter in the study. For instance;
- The MRPs are characterized and so they are organic anion transporters. Most of the substrates for these transporters are extremely charged and do not penetrate the cell membrane.
- Antibodies that work against MRP are often cross-react with another member of multidrug resistance-associated protein family. This issue can be solved by generating monoclonal antibodies against the non-conserved parts of the MRP family.
- The body cells chosen for drug resistance often overexpress multiple transporter genes. The use of certain inhibitors or transfected cells has helped solve this problem.
- It is challenging to get the multidrug resistance-associated protein transfectants giving high expression and products channeled to cell membrane. Most of the cells contain organic anion and this result to background transport activity.
Multidrug resistance-associated protein 2 is helpful in protection against exogenous toxic compounds. The presence of many ABC transporters available offer defense against toxic compounds. The discovery of MRP family has improved the study of MDR in tumor cells and led into interest in the functions of the MRP family members in normal metabolism.
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