{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T13:37:54Z","timestamp":1770903474129,"version":"3.50.1"},"reference-count":74,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2001,12,25]],"date-time":"2001-12-25T00:00:00Z","timestamp":1009238400000},"content-version":"vor","delay-in-days":664,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European Journal of Biochemistry"],"published-print":{"date-parts":[[2000,3]]},"abstract":"<jats:p>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. <jats:italic>MRP2<\/jats:italic> mRNA is expressed at a high level under normal conditions, whereas <jats:italic>MRP3<\/jats:italic> 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\u2013luciferase constructs in HepG2 cells and cloned fragments of 1229 nucleotides and 1287 nucleotides of the <jats:italic>MRP2<\/jats:italic> and <jats:italic>MRP3<\/jats:italic> 5\u2032\u2010flanking regions, respectively. The sequence between nucleotides \u2212517 and \u2212197 was decisive for basal <jats:italic>MRP2<\/jats:italic> expression. Basal promoter activity of <jats:italic>MRP3<\/jats:italic> was only 4% of that measured for <jats:italic>MRP2<\/jats:italic>. At submicromolar concentrations, the histone deacetylase inhibitor trichostatin\u2003A reduced the <jats:italic>MRP2<\/jats:italic> reporter gene activity and expression of the protein. Disruption of microtubules with nocodazole decreased gene and protein expression of MRP2 and increased <jats:italic>MRP3<\/jats:italic> reporter gene activity. The genotoxic 2\u2010acetylaminofluorene decreased the activity of the human <jats:italic>MRP2<\/jats:italic> reporter gene construct, but increased <jats:italic>MRP3<\/jats:italic> gene activity and enhanced the amounts of mRNA and protein of MRP2 and MRP3. Thus, regulation of the expression of these ATP\u2010dependent conjugate export pumps is not co\u2010ordinate, but in part inverse. The inverse regulation of the two MRP isoforms is consistent with their distinct localization, their different mRNA expression under normal and pathophysiological conditions, and their different directions of substrate transport in polarized cells.<\/jats:p>","DOI":"10.1046\/j.1432-1327.2000.01106.x","type":"journal-article","created":{"date-parts":[[2003,3,11]],"date-time":"2003-03-11T18:02:44Z","timestamp":1047405764000},"page":"1347-1358","source":"Crossref","is-referenced-by-count":77,"title":["Characterization of the 5\u2032\u2010flanking region of the human multidrug resistance protein 2 (<i>MRP2<\/i>) gene and its regulation in comparison withthe multidrug resistance protein 3 (<i>MRP3<\/i>) gene"],"prefix":"10.1111","volume":"267","author":[{"given":"Birgit","family":"St\u00f6ckel","sequence":"first","affiliation":[]},{"given":"J\u00f6rg","family":"K\u00f6nig","sequence":"additional","affiliation":[]},{"given":"Anne T.","family":"Nies","sequence":"additional","affiliation":[]},{"given":"Yunhai","family":"Cui","sequence":"additional","affiliation":[]},{"given":"Manuela","family":"Brom","sequence":"additional","affiliation":[]},{"given":"Dietrich","family":"Keppler","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2001,12,25]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(98)92047-X"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.10.1649"},{"key":"e_1_2_7_4_2","first-page":"3537","article-title":"Analysis of expression of cMOAT (MRP2), MRP3, MRP4, and MRP5, homologues of the multidrug resistance\u2010associated protein gene (MRP1), in human cancer cell lines.","volume":"57","author":"Kool M.","year":"1997","journal-title":"Cancer Res."},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1360704"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.271.5252.1126"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.25.15091"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0014-5793(98)00899-0"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510290404"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.12.6914"},{"key":"e_1_2_7_11_2","doi-asserted-by":"crossref","first-page":"27807","DOI":"10.1016\/S0021-9258(18)46856-1","article-title":"The MRP gene encodes an ATP\u2010dependent export pump for leukotriene C4 and structurally related conjugates.","volume":"269","author":"Leier I.","year":"1994","journal-title":"J. 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