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|Title:||Biochemical and molecular characterisation of multidrug resistance protein 4 (MRP4)||Authors:||BAI JING||Keywords:||multi-drug resistance protein; drug resistance; purine analogue; glutathione-S-conjugate; site-directed mutagenesis; substrate specificity||Issue Date:||26-Oct-2003||Citation:||BAI JING (2003-10-26). Biochemical and molecular characterisation of multidrug resistance protein 4 (MRP4). ScholarBank@NUS Repository.||Abstract:||MRP4 is a member of the ATP-binding cassette transporter superfamily. Using cells stably overexpressing MRP4, this study shows that MRP4 confers resistance to anti-cancer drugs 6-thioguanine and gemcitabine. This study also shows that MRP4 can facilitate the efflux of the glutathione conjugate, bimane-glutathione. This transport is ATP-dependant and can be inhibited by substrates of MRP4 and known inhibitors of other MRP transporters. This indicates that MRP4 may play a role in the cellular extrusion of Phase II detoxification metabolites.To gain insight into the role of key amino acids of MRP4 protein for transport organic anions and resistance of chemotherapeutic compounds, site-directed mutagenesis was performed at two highly conserved charged amino acids Glu103, Arg362 and an aromatic residue Trp995 in the transmembrane domain. Our study indicates that these three residues are involved in determinating substrate specificity of MRP4-mediated transport and drug resistance ability of MRP4.||URI:||http://scholarbank.nus.edu.sg/handle/10635/17529|
|Appears in Collections:||Master's Theses (Open)|
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