Multidrug resistance-associated protein (MRP) (MRP)

Multidrug resistance-associated proteins (MRPs) are a group of transmembrane transporters belonging to the ATP-binding cassette (ABC) superfamily, specifically the ABCC subfamily (UniProt, 2024). These proteins function as primary active transporters, utilizing ATP hydrolysis to pump a diverse array of substrates—including organic anions, glutathione, glucuronide, and sulfate conjugates—out of cells (PubMed, 2023). In the context of oncology, MRPs (notably MRP1, MRP2, and MRP4) are frequently overexpressed in tumor cells, where they mediate resistance to various chemotherapeutic agents such as vinca alkaloids, anthracyclines, and antimetabolites by reducing their intracellular accumulation (StatPearls, 2024). Beyond their role in drug resistance, MRPs are vital for physiological detoxification and the transport of endogenous signaling molecules like leukotriene C4 and cyclic nucleotides (NIH, 2023). Mutations in MRP genes are associated with clinical conditions such as Dubin-Johnson syndrome (MRP2) and pseudoxanthoma elasticum (MRP6), highlighting their importance in metabolic homeostasis (PubMed, 2022). Therapeutic strategies involving MRPs focus on developing inhibitors to sensitize cancer cells to chemotherapy, though challenges remain regarding the potential for systemic toxicity and drug-drug interactions due to the widespread physiological expression of these transporters (Nature Reviews Drug Discovery, 2021).

Other names

ATP-binding cassette sub-family CABCCMultidrug resistance proteinCanalicular multispecific organic anion transporter

ATP-dependent primary active transport of various hydrophobic compounds and their conjugates out of the cytoplasm into the extracellular space or into organellar lumens.