Download PDF
Semin Liver Dis 2000; Volume 20(Number 03): 323-338
DOI: 10.1055/s-2000-9387
Copyright © 2000 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Transcriptional Control of Hepatocanalicular Transporter Gene Expression

MICHAEL. MÜLLER
  • From the Division of Gastroenterology and Hepatology, University Hospital Groningen, The Netherlands
Further Information

Publication History

Publication Date:
31 December 2000 (online)

    Permissions and Reprints

ABSTRACT

Transport processes for larger organic solutes at the canalicular membrane are mainly driven by members of the superfamily of ATP-binding cassette (ABC) transporters. The functions of these transporters range from bile component secretion to xenobiotica and phase II-conjugate export. The transcriptional control of the expression of their respective genes differs, and this may be to guarantee tissue specificity, effective response to stress, or changes in substrate concentrations. Inside the nucleus, the concentration of competing and specifically activated transcription factors determines the transcriptional activation in transporter gene expression. Some transcription factors function as sensors for metabolites (LXR, FXR, CAR, SREBP, PPARs), xenobiotics (PPARs, PXR), oxidative stress (NF-κB, AP-1), or DNA damage (p53). Changes in their nuclear concentrations and activity will influence the transcription rates of the respective target genes that contain specific responsive elements in their 5′-promoter/enhancer DNA sequences. Until now little was known about the transcriptional control of most ABC transporter proteins. However, due to the enormous progress in molecular biology, many tools have become recently available to study and understand the ``battle inside the nucleus'' with respect to hepatic transporter gene expression.

KEYWORD

bile secretion - nuclear hormone receptors - ABC-transporter proteins - tumor necrosis factor

REFERENCES

  • 1 Müller M, Roelofsen H, Jansen P LM. Secretion of organic anions by hepatocytes: Involvement of homologues of the multidrug resistance protein.  Semin Liver Dis . 1996;  16 211-220
    PubMedGoogle Scholar
  • 2 Müller M, Jansen P LM. Molecular aspects of hepatobiliary transport.  Am J Physiol . 1997;  272 G1285-G1303
    PubMedGoogle Scholar
  • 3 Oude Elferink R PJ, Meijer D KF, Kuipers F. Hepatobiliary secretion of organic compounds: Molecular mechanisms of membrane transport.  Rev Biomembranes . 1995;  1241 215-268
    PubMedGoogle Scholar
  • 4 Müller M, Jansen P LM. The secretory function of the liver: New insights in hepatobiliary transport.  J Hepatol . 1998;  28 344-354
    CrossrefPubMedGoogle Scholar
  • 5 Klein I, Sarkadi B, Varadi A. An inventory of the human ABC proteins.  Biochim Biophys Acta . 1999;  1461 237-262
    PubMedGoogle Scholar
  • 6 Lewin B. Genes VII. London: Oxford University Press 2000: 649-684
    Google Scholar
  • 7 Di Croce L, Okret S, Kersten S. Steroid and nuclear receptors.  EMBO J . 1999;  18 6201-6210
    CrossrefPubMedGoogle Scholar
  • 8 Mangelsdorf D J, Evans R M. The RXR heterodimers and orphan receptors.  Cell . 1995;  83 841-850
    CrossrefPubMedGoogle Scholar
  • 9 Willy P J, Mangelsdorf D J. Nuclear orphan receptors: The search for novel ligands and signaling pathways.  In: O'Malley BW (ed) Hormones and signaling San Diego, CA: Academic Press, 1998: 307-358
    Google Scholar
  • 10 Waxman D J. P450 gene induction by structurally diverse xenochemicals: Central role of nuclear receptors CAR, PXR, and PPAR.  Arch Biochem Biophys . 1999;  369 11-23
    CrossrefPubMedGoogle Scholar
  • 11 Giguere V. Orphan nuclear receptors: From gene to function.  Endocr Rev . 1999;  20 689-725
    CrossrefPubMedGoogle Scholar
  • 12 Parks D J, Blanchard S G, Bledsoe R K. Bile acids: Natural ligands for an orphan nuclear receptor.  Science . 1999;  284 1365-1368
    CrossrefPubMedGoogle Scholar
  • 13 Makishima M, Okamoto A Y, Repa J J. Identification of a nuclear receptor for bile acids.  Science . 1999;  284 1362-1365
    CrossrefPubMedGoogle Scholar
  • 14 Wang H, Chen J, Hollister K. Endogenous bile acids are ligands for the nuclear receptor FXR/BAR.  Mol Cell . 1999;  3 543-553
    PubMedGoogle Scholar
  • 15 Xu H E, Lambert M H, Montana V G. Molecular recognition of fatty acids by peroxisome proliferator-activated receptors.  Mol Cell . 1999;  3 397-403
    CrossrefPubMedGoogle Scholar
  • 16 Choi H S, Chung M, Tzameli I. Differential transactivation by two isoforms of the orphan nuclear hormone receptor CAR.  J Biol Chem . 1997;  272 23565-23571
    CrossrefPubMedGoogle Scholar
  • 17 Forman B M, Tzameli I, Choi H S. Androstane metabolites bind to and deactivate the nuclear receptor CAR-beta.  Nature . 1998;  395 612-615
    CrossrefPubMedGoogle Scholar
  • 18 Collingwood T N, Urnov F D, Wolffe A P. Nuclear receptors: Coactivators, corepressors and chromatin remodeling in the control of transcription.  J Mol Endocrinol . 1999;  23 255-275
    CrossrefPubMedGoogle Scholar
  • 19 Blumberg B, Sabbagh Jr W, Juguilon H. SXR, a novel steroid and xenobiotic-sensing nuclear receptor.  Genes Dev . 1998;  12 3195-3205
    PubMedGoogle Scholar
  • 20 Kliewer S A, Moore J T, Wade L. An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway.  Cell . 1998;  92 73-82
    CrossrefPubMedGoogle Scholar
  • 21 Lehmann J M, McKee D D, Watson M A. The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions.  J Clin Invest . 1998;  102 1016-1023
    CrossrefPubMedGoogle Scholar
  • 22 Jones S A, Moore L B, Shenk J L. The pregnane X receptor: A promiscuous xenobiotic receptor that has diverged during evolution.  Mol Endocrinol . 2000;  14 27-39
    CrossrefPubMedGoogle Scholar
  • 23 Ishikawa T. The ATP-dependent glutathione S-conjugate export pump.  Trends Biochem Sci . 1992;  17 463-468
    CrossrefPubMedGoogle Scholar
  • 24 Baes M, Gulick T, Choi H S. A new orphan member of the nuclear hormone receptor superfamily that interacts with a subset of retinoic acid response elements.  Mol Cell Biol . 1994;  14 1544-1551
    PubMedGoogle Scholar
  • 25 Honkakoski P, Zelko I, Sueyoshi T. The nuclear orphan receptor CAR-retinoid X receptor heterodimer activates the phenobarbital-responsive enhancer module of the CYP2B gene.  Mol Cell Biol . 1998;  18 5652-5658
    PubMedGoogle Scholar
  • 26 Sueyoshi T, Kawamoto T, Zelko I. The repressed nuclear receptor CAR responds to phenobarbital in activating the human CYP2B6 gene.  J Biol Chem . 1999;  274 6043-6046
    CrossrefPubMedGoogle Scholar
  • 27 Kawamoto T, Sueyoshi T, Zelko I. Phenobarbital-responsive nuclear translocation of the receptor CAR in induction of the CYP2B gene.  Mol Cell Biol . 1999;  19 6318-6322
    PubMedGoogle Scholar
  • 28 Janowski B A, Willy P J, Devi T R. An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha.  Nature . 1996;  383 728-731
    CrossrefPubMedGoogle Scholar
  • 29 Peet D J, Janowski B A, Mangelsdorf D J. The LXRs: A new class of oxysterol receptors.  Curr Opin Genet Dev . 1998;  8 571-575
    CrossrefPubMedGoogle Scholar
  • 30 Janowski B A, Grogan M J, Jones S A. Structural requirements of ligands for the oxysterol liver X receptors LXRalpha and LXRbeta.  Proc Natl Acad Sci USA . 1999;  96 266-271
    CrossrefPubMedGoogle Scholar
  • 31 Repa J J, Mangelsdorf D J. Nuclear receptor regulation of cholesterol and bile acid metabolism.  Curr Opin Biotechnol . 1999;  10 557-563
    CrossrefPubMedGoogle Scholar
  • 32 Peet D J, Turley S D, Ma W. Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXR alpha.  Cell . 1998;  93 693-704
    CrossrefPubMedGoogle Scholar
  • 33 Desvergne B, Wahli W. Peroxisome proliferator-activated receptors: Nuclear control of metabolism.  Endocr Rev . 1999;  20 649-688
    CrossrefPubMedGoogle Scholar
  • 34 Michalik L, Wahli W. Peroxisome proliferator-activated receptors: Three isotypes for a multitude of functions.  Curr Opin Biotechnol . 1999;  10 564-570
    CrossrefPubMedGoogle Scholar
  • 35 Vamecq J, Latruffe N. Medical significance of peroxisome proliferator-activated receptors.  Lancet . 1999;  354 141-148
    CrossrefPubMedGoogle Scholar
  • 36 Miyata K S, McCaw S E, Patel H V. The orphan nuclear hormone receptor LXR alpha interacts with the peroxisome proliferator-activated receptor and inhibits peroxisome proliferator signaling.  J Biol Chem . 1996;  271 9189-9192
    CrossrefPubMedGoogle Scholar
  • 37 Brown M S, Goldstein J L. The SREBP pathway: Regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor.  Cell . 1997;  89 331-340
    CrossrefPubMedGoogle Scholar
  • 38 Brown M S, Goldstein J L. A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood.  Proc Natl Acad Sci USA . 1999;  96 11041-11048
    CrossrefPubMedGoogle Scholar
  • 39 Edwards P A, Ericsson J. Sterols and isoprenoids: Signaling molecules derived from the cholesterol biosynthetic pathway.  Annu Rev Biochem . 1999;  68 157-185
    CrossrefPubMedGoogle Scholar
  • 40 Worgall T S, Sturley S L, Seo T. Polyunsaturated fatty acids decrease expression of promoters with sterol regulatory elements by decreasing levels of mature sterol regulatory element-binding protein.  J Biol Chem . 1998;  273 25537-25540
    CrossrefPubMedGoogle Scholar
  • 41 Zandi E, Karin M. Bridging the gap: Composition, regulation, and physiological function of the IkappaB kinase complex.  Mol Cell Biol . 1999;  19 4547-4551
    PubMedGoogle Scholar
  • 42 Miyamoto S, Verma I M. Rel/NF-kappa B/I kappa B story.  Adv Cancer Res . 1995;  66 255-292
    PubMedGoogle Scholar
  • 43 Baeuerle P A, Baltimore D. NF-kappa B: Ten years after.  Cell . 1996;  87 13-20
    CrossrefPubMedGoogle Scholar
  • 44 Li N, Karin M. Is NF-kappaB the sensor of oxidative stress?.  FASEB J . 1999;  13 1137-1143
    PubMedGoogle Scholar
  • 45 Karin M. How NF-kappaB is activated: The role of the IkappaB kinase (IKK) complex.  Oncogene . 1999;  18 6867-6874
    CrossrefPubMedGoogle Scholar
  • 46 Pahl H L. Activators and target genes of Rel/NF-kappaB transcription factors.  Oncogene . 1999;  18 6853-6866
    CrossrefPubMedGoogle Scholar
  • 47 Das K C, White C W. Activation of NF-kappaB by antineoplastic agents. Role of protein kinase C.  J Biol Chem . 1997;  272 14914-14920
    CrossrefPubMedGoogle Scholar
  • 48 Boland M P, Foster S J, O'Neill L A. Daunorubicin activates NFkappaB and induces kappaB-dependent gene expression in HL-60 promyelocytic and Jurkat T lymphoma cells.  J Biol Chem . 1997;  272 12952-12960
    CrossrefPubMedGoogle Scholar
  • 49 Levine A J. p53, the cellular gatekeeper for growth and division.  Cell . 1997;  88 323-331
    PubMedGoogle Scholar
  • 50 Mowat M R. p53 in tumor progression: Life, death, and everything.  Adv Cancer Res . 1998;  74 25-48
    PubMedGoogle Scholar
  • 51 King K L, Cidlowski J A. Cell cycle regulation and apoptosis.  Annu Rev Physiol . 1998;  60 601-617
    CrossrefPubMedGoogle Scholar
  • 52 Agarwal M L, Taylor W R, Chernov M V. The p53 network.  J Biol Chem . 1998;  273 1-4
    CrossrefPubMedGoogle Scholar
  • 53 Wu H, Lozano G. NF-kappa B activation of p53. A potential mechanism for suppressing cell growth in response to stress.  J Biol Chem . 1994;  269 20067-20074
    PubMedGoogle Scholar
  • 54 Chan H, Bartos D P, Owen-Schaub L B. Activation-dependent transcriptional regulation of the human Fas promoter requires NF-kappaB p50-p65 recruitment.  Mol Cell Biol . 1999;  19 2098-2108
    PubMedGoogle Scholar
  • 55 Hsu S C, Gavrilin M A, Lee H H. NF-kappa B-dependent Fas ligand expression.  Eur J Immunol . 1999;  29 2948-2956
    CrossrefPubMedGoogle Scholar
  • 56 Vos T A, Hooiveld G JEJ, Koning H. Up-regulation of the multidrug resistance genes, mrp1 and mdr1b, and down-regulation of the organic anion transporter, mrp2, and the bile salt transporter, spgp, in endotoxemic rat liver.  Hepatology . 1998;  28 1637-1644
    CrossrefPubMedGoogle Scholar
  • 57 Vos T A, Ros J E, Havinga R. Regulation of hepatic transport systems in rat liver after partial hepatectomy.  Hepatology . 1999;  29 1833-1839
    CrossrefPubMedGoogle Scholar
  • 58 Miranda S, Vollrath V, Wielandt A M. Overexpression of mdr2 gene by peroxisome proliferators in the mouse liver.  J Hepatol . 1997;  26 1331-1339
    CrossrefPubMedGoogle Scholar
  • 59 Chianale J, Vollrath V, Wielandt A M. Fibrates induce mdr2 gene expression and biliary phospholipid secretion in the mouse.  Biochem J . 1996;  314 781-786
    PubMedGoogle Scholar
  • 60 Frijters C M, Ottenhoff R, van Wijland M J. Regulation of mdr2 P-glycoprotein expression by bile salts.  Biochem J . 1997;  321 389-395
    PubMedGoogle Scholar
  • 61 Gupta S, Stravitz R T, Pandak W M. Regulation of the Mdr2 P-glycoprotein expression by bile salts in rats and in primary cultures of rat hepatocytes.  Hepatology . 2000;  32
    PubMedGoogle Scholar
  • 62 Carrella M, Feldman D, Cogoi S. Enhancement of mdr2 gene transcription mediates the biliary transfer of phosphatidylcholine supplied by an increased biosynthesis in the pravastatin-treated rat.  Hepatology . 1999;  29 1825-1832
    CrossrefPubMedGoogle Scholar
  • 63 Hooiveld G JEJ, Vos T A, Scheffer G L. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) induce hepatic expression of the phospholipid translocase mdr2 in rats.  Gastroenterology . 1999;  117 678-687
    PubMedGoogle Scholar
  • 64 Pahl H L. Signal transduction from the endoplasmic reticulum to the cell nucleus.  Physiol Rev . 1999;  79 683-701
    PubMedGoogle Scholar
  • 65 Brown P C, Silverman J A. Characterization of the rat mdr2 promoter and its regulation by the transcription factor Sp1.  Nucleic Acids Res . 1996;  24 3235-3241
    CrossrefPubMedGoogle Scholar
  • 66 Hooiveld G JEJ, Heegsma J, Silverman J A. Induction of hepatic Mdr2 expression by cholesterol synthesis inhibitors (statins) is mediated via Srebps.  Hepatology . 1999;  30 428A
    PubMedGoogle Scholar
  • 67 Gerloff T, Stieger B, Hagenbuch B. The sister of P-glycoprotein represents the canalicular bile salt export pump of mammalian liver.  J Biol Chem . 1998;  273 10046-10050
    CrossrefPubMedGoogle Scholar
  • 68 Strautnieks S S, Bull L N, Knisely A S. A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis.  Nat Genet . 1998;  20 233-238
    CrossrefPubMedGoogle Scholar
  • 69 Lecureur V, Sun D, Hargrove P. Cloning and expression of murine sister of P-glycoprotein reveals a more discriminating transporter than MDR1/P-glycoprotein.  Mol Pharmacol . 2000;  57 24-35
    PubMedGoogle Scholar
  • 70 Green R M, Hoda F, Ward K L. Molecular cloning and characterization of the murine bile salt export pump.  Gene . 2000;  241 117-123
    CrossrefPubMedGoogle Scholar
  • 71 Lee J M, Trauner M, Soroka C J. Expression of the bile salt export pump is maintained after chronic cholestasis in the rat.  Gastroenterology . 2000;  118 163-172
    CrossrefPubMedGoogle Scholar
  • 72 Trauner M, Arrese M, Lee H. Endotoxin downregulates rat hepatic ntcp gene expression via decreased activity of critical transcription factors.  J Clin Invest . 1998;  101 2092-2100
    CrossrefPubMedGoogle Scholar
  • 73 Trauner M, Meier P J, Boyer J L. Molecular pathogenesis of cholestasis.  N Engl J Med . 1998;  339 1217-1227
    CrossrefPubMedGoogle Scholar
  • 74 Gerloff T, Geier A, Stieger B. Differential expression of basolateral and canalicular organic anion transporters during regeneration of rat liver.  Gastroenterology . 1999;  117 1408-1415
    PubMedGoogle Scholar
  • 75 Kauffmann H M, Keppler D, Kartenbeck J. Induction of cMrp/cMoat gene expression by cisplatin, 2-acetylaminofluorene, or cycloheximide in rat hepatocytes.  Hepatology . 1997;  26 980-985
    PubMedGoogle Scholar
  • 76 Cui Y, König J, Buchholz J K. Drug resistance and ATP-dependent conjugate transport mediated by the apical multidrug resistance protein, MRP2, permanently expressed in human and canine cells.  Mol Pharmacol . 1999;  55 929-937
    PubMedGoogle Scholar
  • 77 Tanaka T, Uchiumi T, Hinoshita E. The human multidrug resistance protein 2 gene: Functional characterization of the 5′-flanking region and expression in hepatic cells.  Hepatology . 1999;  30 1507-1512
    CrossrefPubMedGoogle Scholar
  • 78 Kauffmann H M, Schrenk D. Sequence analysis and functional characterization of the 5′- flanking region of the rat multidrug resistance protein 2 (mrp2) gene.  Biochem Biophys Res Commun . 1998;  245 325-331
    CrossrefPubMedGoogle Scholar
  • 79 Stöckel B, König J, Nies A T. Characterization of the 5′-flanking region of the human multidrug resistance protein 2 (MRP2) gene and its regulation in comparison with the multidrug resistance protein 3 (MRP3) gene.  Eur J Biochem . 2000;  267 1347-1358
    CrossrefPubMedGoogle Scholar
  • 80 Denson L ASJ, Auld K L, Schiek D S. Interleukin-1β suppresses retinoid transactivation of two hepatic transporter genes involved in bile formation.  J Biol Chem . 2000;  275 8835-8843
    CrossrefPubMedGoogle Scholar
  • 81 Cole S PC, Deeley R G. Multidrug resistance mediated by the ATP-binding cassette transporter protein MRP.  BioEssays . 1998;  20 931-940
    CrossrefPubMedGoogle Scholar
  • 82 König J, Nies A T, Cui Y. Conjugate export pumps of the multidrug resistance protein (MRP) family: Localization, substrate specificity, and MRP2-mediated drug resistance.  Biochim Biophys Acta . 1999;  1461 377-394
    PubMedGoogle Scholar
  • 83 Roelofsen H, Hooiveld G JEJ, Koning H. Glutathione S-conjugate transport in hepatocytes entering the cell cycle is preserved by a switch in expression from the apical MRP2 to the basolateral MRP1 transporting protein.  J Cell Sci . 1999;  112 1395-1404
    PubMedGoogle Scholar
  • 84 Roelofsen H, Vos T A, Schippers I J. Increased level of the multidrug resistance protein in lateral membranes of proliferating hepatocyte-derived cells.  Gastroenterology . 1997;  112 511-521
    PubMedGoogle Scholar
  • 85 Yamane Y, Furuichi M, Song R. Expression of multidrug resistance Protein/GS-X pump and gamma-glutamylcysteine synthetase genes is regulated by oxidative stress.  J Biol Chem . 1998;  273 31075-31085
    CrossrefPubMedGoogle Scholar
  • 86 Kuo M T, Bao J, Furuichi M. Frequent coexpression of MRP/GS-X pump and gamma- glutamylcysteine synthetase mRNA in drug-resistant cells, untreated tumor cells, and normal mouse tissues.  Biochem Pharmacol . 1998;  55 605-615
    CrossrefPubMedGoogle Scholar
  • 87 Zhu Q C, Center M S. Cloning and sequence analysis of the promoter region of the MRP gene of HL60 cells isolated for resistance to adriamycin.  Cancer Res . 1994;  54 4488-4492
    PubMedGoogle Scholar
  • 88 Zhu Q C, Center M S. Evidence that SP1 modulates transcriptional activity of the multidrug resistance-associated protein gene.  DNA Cell Biol . 1996;  15 105-111
    PubMedGoogle Scholar
  • 89 Wang Q, Beck W T. Transcriptional suppression of multidrug resistance-associated protein (MRP) gene expression by wild-type p53.  Cancer Res . 1998;  58 5762-5769
    PubMedGoogle Scholar
  • 90 Norris M D, Bordow S B, Marshall G M. Expression of the gene for multidrug-resistance-associated protein and outcome in patients with neuroblastoma.  N Engl J Med . 1996;  334 231-238
    CrossrefPubMedGoogle Scholar
  • 91 Haber M, Bordow S B, Gilbert J. Altered expression of the MYCN oncogene modulates MRP gene expression and response to cytotoxic drugs in neuroblastoma cells.  Oncogene . 1999;  18 2777-2782
    CrossrefPubMedGoogle Scholar
  • 92 Ogawa K, Suzuki H, Hirohashi T. Characterization of the inducible nature of MRP3 in rat liver.  Amer J Physiol . 2000;  278 G438-G446
    PubMedGoogle Scholar
  • 93 Hirohashi T, Suzuki H, Takikawa H. ATP-dependent transport of bile salts by rat multidrug resistance-associated protein 3 (Mrp3).  J Biol Chem . 2000;  275 2905-2910
    CrossrefPubMedGoogle Scholar
  • 94 Kiuchi Y, Suzuki H, Hirohashi T. cDNA cloning and inducible expression of human multidrug resistance associated protein 3 (MRP3).  FEBS Lett . 1998;  433 149-152
    CrossrefPubMedGoogle Scholar
  • 95 Hirohashi T, Suzuki H, Ito K. Hepatic expression of multidrug resistance-associated protein- like proteins maintained in eisai hyperbilirubinemic rats.  Mol Pharmacol . 1998;  53 1068-1075
    PubMedGoogle Scholar
  • 96 König J, Rost D, Cui Y. Characterization of the human multidrug resistance protein isoform MRP3 localized to the basolateral hepatocyte membrane.  Hepatology . 1999;  29 1156-1163
    CrossrefPubMedGoogle Scholar
  • 97 Fromm M F, Leake B, Roden D M. Human MRP3 transporter: Identification of the 5′-flanking region, genomic organization and alternative splice variants.  Biochim Biophys Acta . 1999;  1415 369-374
    PubMedGoogle Scholar
  • 98 Hu Z, Jin S, Scotto K W. Transcriptional activation of the MDR1 gene by UV irradiation. Role of NF-Y and Sp1.  J Biol Chem . 2000;  275 2979-2985
    CrossrefPubMedGoogle Scholar
  • 99 Silverman J A, Thorgeirsson S S. Regulation and function of the multidrug resistance genes in liver.  Prog Liver Dis . 1995;  13 101-123
    PubMedGoogle Scholar
  • 100 Ohga T, Koike K, Ono M. Role of the human Y box-binding protein YB-1 in cellular sensitivity to the DNA-damaging agents cisplatin, mitomycin C, and ultraviolet light.  Cancer Res . 1996;  56 4224-4228
    PubMedGoogle Scholar
  • 101 Ohga T, Uchiumi T, Makino Y. Direct involvement of the Y-box binding protein YB-1 in genotoxic stress-induced activation of the human multidrug resistance 1 gene.  J Biol Chem . 1998;  273 5997-6000
    CrossrefPubMedGoogle Scholar
  • 102 Fry C J, Farnham P J. Context-dependent transcriptional regulation.  J Biol Chem . 1999;  274 29583-29586
    CrossrefPubMedGoogle Scholar
  • 103 Thottassery J V, Sun D, Zambetti G P. Sp1 and egr-1 have opposing effects on the regulation of the rat Pgp2/mdr1b gene.  J Biol Chem . 1999;  274 3199-3206
    CrossrefPubMedGoogle Scholar
  • 104 Thottassery J V, Zambetti G P, Arimori K. p53-dependent regulation of MDR1 gene expression causes selective resistance to chemotherapeutic agents.  Proc Natl Acad Sci USA . 1997;  94 11037-11042
    CrossrefPubMedGoogle Scholar
  • 105 Zhou G, Kuo M T. Wild-type p53-mediated induction of rat mdr1b expression by the anticancer drug daunorubicin.  J Biol Chem . 1998;  273 15387-15394
    CrossrefPubMedGoogle Scholar
  • 106 Nakatsukasa H, Silverman J A, Gant T W. Expression of multidrug resistance genes in rat liver during regeneration and after carbon tetrachloride intoxication.  Hepatology . 1993;  18 1202-1207
    CrossrefPubMedGoogle Scholar
  • 107 Zhou G, Kuo M T. NF-ΚB-mediated induction of mdr1b expression by insulin in rat hepatoma cells.  J Biol Chem . 1997;  272 15174-15183
    CrossrefPubMedGoogle Scholar
  • 108 Thevenod F, Friedmann J M, Katsen A D. Up-regulation of multidrug resistance P-glycoprotein via nuclear factor-kappaB activation protects kidney proximal tubule cells from cadmium- and reactive oxygen species-induced apoptosis.  J Biol Chem . 2000;  275 1887-1896
    CrossrefPubMedGoogle Scholar
  • 109 Ros J E, Geuken M, Schuetz J D. TNFα-mediated up-regulation of the multidrug resistance gene Mdr1b but not of Mrp1 in rat hepatocytes is dependent on NF-κB activation.  Hepatology . 1999;  30 462A
    CrossrefPubMedGoogle Scholar
  • 110 Schuetz E G, Schinkel A H, Relling M V. P-glycoprotein: A major determinant of rifampicin-inducible expression of cytochrome P4503A in mice and humans.  Proc Natl Acad Sci USA . 1996;  93 4001-4005
    CrossrefPubMedGoogle Scholar
  • 111 Schuetz E G, Umbenhauer D R, Yasuda K. Altered expression of hepatic cytochromes P-450 in mice deficient in one or more mdr1 genes.  Mol Pharmacol . 2000;  57 188-197
    PubMedGoogle Scholar
  • 112 Schinkel A H, Smit J JM, van Tellingen O. Disruption of the mouse mdr1a p-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs.  Cell . 1994;  77 491-502
    CrossrefPubMedGoogle Scholar
  • 113 Schinkel A H, Mayer U, Wagenaar E. Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-glycoproteins.  Proc Natl Acad Sci USA . 1997;  94 4028-4033
    CrossrefPubMedGoogle Scholar
  • 114 Blumberg B, Evans R M. Orphan nuclear receptors-new ligands and new possibilities.  Genes Dev . 1998;  12 3149-3155
    CrossrefPubMedGoogle Scholar
  • 115 The Nuclear Receptor Nomenclature Committee.. A unified nomenclature system for the nuclear receptor superfamily.  Cell . 1999;  97 161-163
    CrossrefPubMedGoogle Scholar
  • 116 Chiang J Y, Stroup D. Identification and characterization of a putative bile acid-responsive element in cholesterol 7 alpha-hydroxylase gene promoter.  J Biol Chem . 1994;  269 17502-17507
    PubMedGoogle Scholar
  • 117 Savas U, Griffin K J, Johnson E F. Molecular mechanisms of cytochrome P-450 induction by xenobiotics: An expanded role for nuclear hormone receptors.  Mol Pharmacol . 1999;  56 851-857
    PubMedGoogle Scholar
  • 118 Crestani M, Sadeghpour A, Stroup D. Transcriptional activation of the cholesterol 7alpha-hydroxylase gene (CYP7A) by nuclear hormone receptors.  J Lipid Res . 1998;  39 2192-2200
    PubMedGoogle Scholar
  • 119 Stroup D, Chiang J Y. HNF4 and COUP-TFII interact to modulate transcription of the cholesterol 7alpha-hydroxylase gene (CYP7A1).  J Lipid Res . 2000;  41 1-11
    PubMedGoogle Scholar
  • 120 Rastinejad F, Wagner T, Zhao Q. Structure of the RXR-RAR DNA-binding complex on the retinoic acid response element DR1.  EMBO J . 2000;  19 1045-1054
    CrossrefPubMedGoogle Scholar
  • 121 Silverman J A, Hill B A. Characterization of the basal and carcinogen regulatory elements of the rat mdr1b promoter.  Mol Carcinog . 1995;  13 50-59
    PubMedGoogle Scholar
  • 122 Brown P C, Thorgeirsson S S, Silverman J A. Cloning and regulation of the rat mdr2 gene.  Nucleic Acids Res . 1993;  21 3885-3891
    PubMedGoogle Scholar
  • 123 Ericsson J, Jackson S M, Lee B C. Sterol regulatory element binding protein binds to a cis element in the promoter of the farnesyl diphosphate synthase gene.  Proc Natl Acad Sci USA . 1996;  93 945-950
    CrossrefPubMedGoogle Scholar
  • 124 Overdier D G, Porcella A, Costa R H. The DNA-binding specificity of the hepatocyte nuclear factor 3/forkhead domain is influenced by amino-acid residues adjacent to the recognition helix.  Mol Cell Biol . 1994;  14 2755-2766
    PubMedGoogle Scholar
  • 125 Trauner M, Arrese M, Soroka C J. The rat canalicular conjugate export pump (Mrp2) is down-regulated in intrahepatic and obstructive cholestasis.  Gastroenterology . 1997;  113 255-264
    CrossrefPubMedGoogle Scholar
  • 126 Courtois A, Payen L, Guillouzo A. Up-regulation of multidrug resistance-associated protein 2 (MRP2) expression in rat hepatocytes by dexamethasone.  FEBS Lett . 1999;  459 381-385
    CrossrefPubMedGoogle Scholar
  • 127 Broccardo C, Luciani M, Chimini G. The ABCA subclass of mammalian transporters.  Biochim Biophys Acta . 1999;  1461 395-404
    PubMedGoogle Scholar
  • 128 Klucken J, Buchler C, Orso E. ABCG1 (ABC8), the human homolog of the drosophila white gene, is a regulator of macrophage cholesterol and phospholipid transport.  Proc Natl Acad Sci USA . 2000;  97 817-822
    CrossrefPubMedGoogle Scholar
  • 129 Kool M, van der Linden M, de Haas M. Expression of human MRP6, a homologue of the multidrug resistance protein gene MRP1, in tissues and cancer cells.  Cancer Res . 1999;  59 175-182
    PubMedGoogle Scholar
  • 130 Madon J, Hagenbuch B, Landmann L. Transport function and hepatocellular localization of mrp6 in rat liver.  Mol Pharmacol . 2000;  57 634-641
    PubMedGoogle Scholar
  • 131 Schroepfer Jr G J. Oxysterols: Modulators of cholesterol metabolism and other processes.  Physiol Rev . 2000;  80 361-554
    PubMedGoogle Scholar
  • 132 Russell D W. Nuclear orphan receptors control cholesterol catabolism.  Cell . 1999;  97 539-542
    CrossrefPubMedGoogle Scholar
  • 133 Gustafsson J A. Seeking ligands for lonely orphan receptors.  Science . 1999;  284 1285-1286
    CrossrefPubMedGoogle Scholar
  • 134 Budihardjo I, Oliver H, Lutter M. Biochemical pathways of caspase activation during apoptosis.  Annu Rev Cell Dev Biol . 1999;  15 269-290
    CrossrefPubMedGoogle Scholar
  • 135 Bradham C A, Plumpe J, Manns M P. Mechanisms of hepatic toxicity. I. TNF-induced liver injury.  Am J Physiol . 1998;  275 G387-G392
    PubMedGoogle Scholar
  • 136 Wallach D, Varfolomeev E E, Malinin N L. Tumor necrosis factor receptor and Fas signaling mechanisms.  Annu Rev Immunol . 1999;  17 331-367
    CrossrefPubMedGoogle Scholar
  • 137 Trauner M, Meier P J, Boyer J L. Molecular regulation of hepatocellular transport systems in cholestasis.  J Hepatol . 1999;  31 165-178
    CrossrefPubMedGoogle Scholar
  • 138 Morgan E T, Sewer M B, Iber H. Physiological and pathophysiological regulation of cytochrome P450.  Drug Metab Dispos . 1998;  26 1232-1240
    PubMedGoogle Scholar
  • 139 Smit J JM, Mol C AAM, van Deemter L. Characterization of the promoter region of the human MDR3 p-glycoprotein gene.  Biochim Biophys Acta . 1995;  1261 44-56
    PubMedGoogle Scholar