PMID- 10573531 OWN - NLM STAT- MEDLINE DCOM- 19991216 LR - 20211203 IS - 0270-9139 (Print) IS - 0270-9139 (Linking) VI - 30 IP - 6 DP - 1999 Dec TI - The human multidrug resistance protein 2 gene: functional characterization of the 5'-flanking region and expression in hepatic cells. PG - 1507-12 AB - The human multidrug resistance protein 2 (MRP2), also termed as the canalicular multispecific organic anion transporter (cMOAT), is a member of the adenosine triphosphate-binding cassette transporter superfamily. In the liver, MRP2 mediates the multispecific efflux of various types of organic anions, including glucuronate, sulfate, and glutathione conjugates, across the canalicular hepatocyte membrane to the bile. To investigate how the MRP2 gene is expressed in liver cells, the 5'-flanking region of the human MRP2 gene was isolated from a human placental genomic library. Sequence analysis of the MRP2 promoter showed a number of consensus binding sites for both ubiquitous and liver-enriched transcription factors. Transfection of human hepatic HepG2 cells with a series of 5'-deleted promoter luciferase constructs identified a putative silencer element localized in the -1,659/-491 region and a liver-specific positive regulatory element localized in the -491/-258 region. This latter region contained the liver-abundant transcription factor CCAAT-enhancer binding protein beta (C/EBPbeta). The transcriptional activity of the promoter construct containing a mutation in the C/EBPbeta binding site was significantly decreased in HepG2 cells. This study suggests that C/EBPbeta (-356 to -343) may regulate the liver expression of the MRP2 gene. FAU - Tanaka, T AU - Tanaka T AD - Department of Biochemistry, Kyushu University School of Medicine, Fukuoka, University of Occupational Environmental Health, Kitakyushu, Japan. FAU - Uchiumi, T AU - Uchiumi T FAU - Hinoshita, E AU - Hinoshita E FAU - Inokuchi, A AU - Inokuchi A FAU - Toh, S AU - Toh S FAU - Wada, M AU - Wada M FAU - Takano, H AU - Takano H FAU - Kohno, K AU - Kohno K FAU - Kuwano, M AU - Kuwano M LA - eng SI - GENBANK/AF144630 PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Hepatology JT - Hepatology (Baltimore, Md.) JID - 8302946 RN - 0 (ABCC2 protein, human) RN - 0 (ATP Binding Cassette Transporter, Subfamily B) RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (CCAAT-Enhancer-Binding Proteins) RN - 0 (DNA-Binding Proteins) RN - 0 (Multidrug Resistance-Associated Protein 2) RN - 0 (Nuclear Proteins) RN - 0 (RNA, Messenger) RN - 9EI49ZU76O (multidrug resistance protein 3) SB - IM MH - ATP Binding Cassette Transporter, Subfamily B/chemistry/*genetics/metabolism MH - ATP-Binding Cassette Transporters/chemistry/*genetics/metabolism MH - Amino Acid Sequence MH - Base Sequence MH - CCAAT-Enhancer-Binding Proteins MH - Cloning, Molecular MH - DNA-Binding Proteins/physiology MH - Drug Resistance, Multiple/*genetics MH - Gene Expression Regulation/*genetics MH - Gene Silencing MH - Genes, Reporter MH - Genomic Library MH - Humans MH - Liver/cytology/*metabolism MH - Molecular Sequence Data MH - Multidrug Resistance-Associated Protein 2 MH - Nuclear Proteins/physiology MH - Promoter Regions, Genetic/genetics MH - RNA, Messenger/analysis/genetics MH - Response Elements/genetics MH - Sequence Deletion/genetics MH - Transfection MH - Tumor Cells, Cultured EDAT- 1999/11/26 00:00 MHDA- 1999/11/26 00:01 CRDT- 1999/11/26 00:00 PHST- 1999/11/26 00:00 [pubmed] PHST- 1999/11/26 00:01 [medline] PHST- 1999/11/26 00:00 [entrez] AID - S0270913999005212 [pii] AID - 10.1002/hep.510300617 [doi] PST - ppublish SO - Hepatology. 1999 Dec;30(6):1507-12. doi: 10.1002/hep.510300617.