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Updated: Aug 6, 2026
ABCG5/G8 Crystallization in a Lipidic Bicelle Environment for X-Ray Crystallography
Published on: August 25, 2023
ABCC10, ABCC11, and ABCC12
Gary D Kruh1, Yanping Guo, Elizabeth Hopper-Borge
1Medical Science Division, Fox Chase Cancer Center, Philadelphia, PA 19111, USA. Gary.Kruh@fccc.edu
Abstract:
Multidrug resistance protein (MRP)7, MRP8, and MRP9 (gene symbols ABCC10, ABCC11, and ABCC12) are recently identified members of the MRP family that are at relatively early stages of investigation. Of these proteins, a physiological function has only been established for MRP8, for which a single nucleotide polymorphism determines wet vs dry earwax type. MRP7 and MRP8 are lipophilic anion pumps that are able to confer resistance to chemotherapeutic agents. MRP7 is competent in the transport of the glucuronide E(2)17betaG, and its resistance profile, which includes several natural product anticancer agents, is distinguished by the taxane docetaxel. MRP8 is able to transport a diverse range of lipophilic anions, including cyclic nucleotides, E(2)17betaG, steroid sulfates such as dehydroepiandrosterone (DHEAS) and E(1)S, glutathione conjugates such as leukotriene C4 and dinitrophenyl-S-glutathione, and monoanionic bile acids. However, the constituent of earwax that is susceptible to transport by MRP8 has not been identified. MRP8 has complex interactions with its substrates, as indicated by the nonreciprocal ability of DHEAS to stimulate E(2)17betaG transport. Similar to the case for other MRPs that possess only two membrane spanning domains (MRP4 and MRP5), MRP8 is a cyclic nucleotide efflux pump that is able to confer resistance to nucleoside-based agents, such as PMEA and 5FU. The functional characteristics of MRP9 are currently unknown.
Insights
Multidrug resistance-associated protein (MRP)7 and MRP8 are lipophilic anion transporters that confer resistance to chemotherapy. MRP8 also influences earwax type, while MRP9 function remains unknown.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Multidrug resistance-associated protein (MRP)7, MRP8, and MRP9 are newly identified members of the MRP transporter family.
- Their physiological roles and functional characteristics are largely uncharacterized, representing an early stage of investigation.
Purpose of the Study:
- To elucidate the functional characteristics and substrate specificities of MRP7, MRP8, and MRP9.
- To understand their potential roles in drug resistance and physiological processes.
Main Methods:
- Functional transport assays were employed to determine the substrate profiles of MRP7 and MRP8.
- Gene expression analysis and genetic association studies were used to investigate MRP8's role in earwax determination.
Main Results:
- MRP7 and MRP8 function as lipophilic anion pumps, conferring resistance to chemotherapeutic agents like docetaxel.
- MRP8 transports various substrates including cyclic nucleotides, steroid sulfates (DHEAS, E(1)S), glutathione conjugates, and bile acids.
- A single nucleotide polymorphism in MRP8 is linked to wet vs. dry earwax type.
- MRP8 exhibits complex substrate interactions, influencing transport rates non-reciprocally.
- MRP8 functions as a cyclic nucleotide efflux pump, conferring resistance to nucleoside analogs (PMEA, 5FU).
- The functional characteristics of MRP9 are currently unknown.
Conclusions:
- MRP7 and MRP8 are functionally characterized as drug efflux pumps with distinct substrate specificities, implicated in chemotherapy resistance.
- MRP8 plays a role in a human physiological trait (earwax type) and exhibits complex transport kinetics.
- Further investigation is required to determine the function of MRP9.
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