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Characterization of the 5′-flanking region of the human multidrug resistance protein 2 (MRP2) gene and its regulation in comparison withthe multidrug resistance protein 3 (MRP3) gene by Birgit Stöckel; Jörg König; Anne T. Nies; Yunhai Cui; Manuela Brom; Dietrich Keppler is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

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The multidrug resistance proteins MRP2 (symbol ABCC2) and MRP3 (symbol ABCC3) are conjugate export pumps expressed in hepatocytes. MRP2 is localized exclusively to the apical membrane and MRP3 to the basolateral membrane. __MRP2__ mRNA is expressed at a high level under normal conditions, whereas __MRP3__ mRNA expression is low and increases only when secretion across the apical membrane by MRP2 is impaired. We studied some of the regulatory properties of the two human genes using transient transfection assays with promoter–luciferase constructs in HepG2 cells and cloned fragments of 1229 nucleotides and 1287 nucleotides of the __MRP2__ and __MRP3__ 5′‐flanking regions, respectively. The sequence between nucleotides −517 and −197 was decisive for basal __MRP2__ expression. Basal promoter activity of __MRP3__ was only 4% of that measured for __MRP2__. At submicromolar concentrations, the histone deacetylase inhibitor trichostatin A reduced the __MRP2__ reporter gene activity and expression of the protein. Disruption of microtubules with nocodazole decreased gene and protein expression of MRP2 and increased __MRP3__ reporter gene activity. The genotoxic 2‐acetylaminofluorene decrease

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Author

Birgit Stöckel; Jörg König; Anne T. Nies; Yunhai Cui; Manuela Brom; Dietrich Keppler

Publisher

John Wiley and Sons; Springer; Wiley (Blackwell Publishing); Springer-Verlag; Blackwell Publishing Inc.; Springer Verlag; Wiley; Springer Science and Business Media LLC (ISSN 1432-1327)

Published

2000

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)